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1
HATANO, MOTOHISA. "Studies on free liver cells of rats. Effect of various drugs." Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics 18, n.º 1 (1987): 87–88. http://dx.doi.org/10.3999/jscpt.18.87.
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Rashid, M. S., Faheem Hadi, Zoya Muzaffar, H. M. Asif, Naveed Akhtar, Memoona Zahra, Maqbool, L. Sumreen, T. Shamim e A. Malik. "Cytotoxic Effect of Kigelia Africana Plant Extracts on Liver Cancer Cells". Pakistan Journal of Medical and Health Sciences 16, n.º 10 (30 de outubro de 2022): 68–71. http://dx.doi.org/10.53350/pjmhs22161068.
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Background: Various medicinal plants have much efficacious value as treatment of many fatal conditions including cancer. Kigelia africana has known therapeutic efficacy in different ailments and has been used as traditional medicine since ages. Aim: To evaluate anticancer property of any drug or plant extract including HepG2 cell line. Methodology: Anticancer activity of n-hexane and ethanolic extracts of Kigelia africana was checked. IC50 was evaluated via MTT assay, crystal violet assay was performed to check the viability of cells and trypan blue assay to count dead cells. Furthermore, muse analysis was performed using count and viability kit to count total living as well non-living cells. Results: Cancer cells of HepG2 cell line showed reduced viability and proliferation with increased apoptosis when treated with Kigelia extracts. Conclusion: Many drugs have been proved as anticancer but with severe side effects. Thus, phytoextracts have been tested in this study to evaluate their anti-cancer activity so minimize the side effect. Kigelia africana extracts were found to be effective against liver cancer cells. Keyword: Kigelia africana, HepG2, MTT, liver cancer, anticancer drug, plant based drugs.
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Ting, Liu, Liu Juan e Yang Jian Qiong. "Effective Components of Hepatoprotective Drugs". Applied Mechanics and Materials 633-634 (setembro de 2014): 533–36. http://dx.doi.org/10.4028/www.scientific.net/amm.633-634.533.
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Pathological changes in animal models of autoimmune hepatitis and liver cells were similar to the mechanism of injury and viral hepatitis, the thesis of the active component of several common liver substances studied, wild chrysanthemum extract has anti-bacterial, anti-viral, pharmacological effects such as anti-inflammatory and immune liver and nerve protection, Dicliptera polysaccharide with excellent hepatoprotective activity of the liver that can be used as an adjunct to clinical medicine. Introduction
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Li, Rui, Chengyong Dong, Keqiu Jiang, Rui Sun, Yang Zhou, Zeli Yin, Jiaxin Lv, Junlin Zhang, Qi Wang e Liming Wang. "Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux". Carcinogenesis 41, n.º 11 (11 de maio de 2020): 1583–91. http://dx.doi.org/10.1093/carcin/bgaa029.
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Abstract Liver cancer is a major threat to human life and health, and chemotherapy has been the standard non-surgical treatment for liver cancer. However, the emergence of drug resistance of liver cancer cells has hindered the therapeutic effect of chemical drugs. The discovery of exosomes has provided new insights into the mechanisms underlying tumour cell resistance. In this study, we aimed to determine the proteins associated with drug resistance in tumour cells and to elucidate the underlying mechanisms. We found that Rab27B expression in drug (5-fluorouracil, 5Fu)-resistant Bel7402 (Bel/5Fu) cells increased significantly compared with that in drug-sensitive Bel7402 cells. In addition, Bel/5Fu cells secreted more exosomes under 5Fu stimulation. The number of exosomes secreted by Bel/5Fu cells significantly reduced after knocking down Rab27B, and the cellular concentration of 5Fu increased, enhancing its therapeutic effect. We also found that the administration of classical drug efflux pump (P-glycoprotein, P-gp) inhibitors together with knockdown of Rab27B further improved the therapeutic effects of chemotherapy drugs. In conclusion, our findings suggest that Rab27B could be a new therapeutic target in liver cancer.
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Renovaldi, Dede, e Abdul Khalik Adam. "Potential of Sweet Basil (Ocimum basilicum) as a Hepatoprotector Agent for Liver Injury Related to Drugs". Muhammadiyah Medical Journal 1, n.º 2 (16 de novembro de 2020): 63. http://dx.doi.org/10.24853/mmj.1.2.63-68.
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The use of drugs is one of the most common causes of liver injury, because the liver is the main organ that metabolizes drugs. Little is currently done if there is a liver injury due to the hepatotoxic side effects of a drug. Herbal plants have active natural compounds that have pharmacological effects so they are widely used as alternative treatments. Sweet basil (Ocimum basilicum) is one of the most cultivated plants in Asia. Studies on the use of Ocimum basilicum in medicine have been carried out, one of which is the hepatoprotector effect. Studies indicate that Ocimum basilicum is rich in high antioxidant content (flavonoids, saponins, tannins, sterols, triterpenes, and rosmaniric acid) capable of providing hepatoprotector effects by helping the regeneration process of hepatocyte cells that are damaged by hepatotoxic agents and significantly decreasing liver damage biomarkers. The purpose of this review is to explain the potential of Ocimum basilicum as a hepatoprotective agent for liver injury associated with drugs. The conclusion of this review is Ocimum basilicum has high potential in its utilization as a hepatoprotector against liver injury mainly related to the consumption of drugs that have hepatotoxic effects.
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Renovaldi, Dede, e Abdul Khalik Adam. "Potential of Sweet Basil (Ocimum basilicum) as a Hepatoprotector Agent for Liver Injury Related to Drugs". Muhammadiyah Medical Journal 1, n.º 2 (16 de novembro de 2020): 21. http://dx.doi.org/10.24853/mmj.1.2.21-26.
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The use of drugs is one of the most common causes of liver injury, because the liver is the main organ that metabolizes drugs. Little is currently done if there is a liver injury due to the hepatotoxic side effects of a drug. Herbal plants have active natural compounds that have pharmacological effects so they are widely used as alternative treatments. Sweet basil (Ocimum basilicum) is one of the most cultivated plants in Asia. Studies on the use of Ocimum basilicum in medicine have been carried out, one of which is the hepatoprotector effect. Studies indicate that Ocimum basilicum is rich in high antioxidant content (flavonoids, saponins, tannins, sterols, triterpenes, and rosmaniric acid) capable of providing hepatoprotector effects by helping the regeneration process of hepatocyte cells that are damaged by hepatotoxic agents and significantly decreasing liver damage biomarkers. The purpose of this review is to explain the potential of Ocimum basilicum as a hepatoprotective agent for liver injury associated with drugs. The conclusion of this review is Ocimum basilicum has high potential in its utilization as a hepatoprotector against liver injury mainly related to the consumption of drugs that have hepatotoxic effects.
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Liao, Wei, Yan Tang, Zhengcui Hu, Chunyan Wang, Yi Chen, Yi Zhang e Wenhan Fan. "Preparation of Galactosyl Nanoparticles and Their Targeting Efficiency to Hepatocellular Carcinoma". Journal of Nanoscience and Nanotechnology 21, n.º 2 (1 de fevereiro de 2021): 987–94. http://dx.doi.org/10.1166/jnn.2021.18666.
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Liver diseases seriously endanger people’s physical health, especially liver cancer, and its morbidity and mortality have increased year by year. The reason why liver cancer is difficult to cure is that in addition to the low lethality of cancer drugs to cancer cells, another important factor is that the drugs do not have liver targeting, and there is no way to efficiently deliver anti-cancer drugs to the liver lesions. Hepatocytes can specifically recognize galactose, therefore the galactosyl liver-targeted drug carrier can deliver the drug to the liver in a targeted manner, so that the drug can be directed to the liver, reduce the dose and times of drug administration, reduce toxic side effects, and reduce the adverse reactions of patients, which is of great significance for the treatment of liver cancer. In this thesis, paclitaxel long-circulating nano-liposomes targeting liver cancer constructed with galactose as raw materials can improve the pharmacokinetics and tissue distribution of traditional formulations of paclitaxel, and enhance the safety and tumor suppressive effect of paclitaxel in vivo.
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ÖNAL, Müge Gülcihan. "A New Approach: Treatment with Sodium Vanadate and Cisplatin Combination for Human Hepatocellular Carcinoma". Proceedings 40, n.º 1 (25 de dezembro de 2019): 14. http://dx.doi.org/10.3390/proceedings2019040014.
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The most common primary liver malignancy is hepatocellular carcinoma. Various chemotherapy drugs are used for treatment. These drugs have high toxicity to liver tissue. More effective, less toxic options should be preferred for treatment. The aim of this study is to investigate the cytotoxic effect of cisplatin and sodium vanadate combination (NaV) in hepatocellular carcinoma. The hepatocellular cancer cell line (HepG2) was used in this study. Increased concentration of cisplatin and a selected concentration of sodium vanadate were treated to HepG2 cells for 24- and 72-hours incubation times. The proliferation of HepG2 cells decreased with the combination of NaV and cisplatin. While cisplatin was effective in 10–4 M concentration in the proliferation of HepG2 cells, 10–4 M cisplatin with 10–3 M NaV in combination was less effective in the proliferation of HepG2 cells. According to these results, NaV and cisplatin show toxic effects on hepatocellular carcinoma cells. However, the combination of cisplatin and NaV has a less toxic effect than cisplatin and NaV on hepatocellular carcinoma cells.
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Tian, Shiliu, Rui Su, Ke Wu, Xuhan Zhou, Jaydutt V. Vadgama e Yong Wu. "Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells". Journal of Personalized Medicine 12, n.º 8 (16 de agosto de 2022): 1318. http://dx.doi.org/10.3390/jpm12081318.
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Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer.
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Hatta, Fazleen Haslinda Mohd, Ruhil Nadirah Che Omar, Mohd Ikhwan Ismail, Rosmadi Mohd Yusoff e Mohd Shihabuddin Ahmad Noorden. "Determining the Population Doubling Time of HepG2 and Huh-7 Cells and the Toxic Effect of Dimethyl Sulfoxide (DMSO)". ASM Science Journal 17 (7 de novembro de 2022): 1–5. http://dx.doi.org/10.32802/asmscj.2022.1238.
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Developing cell lines that carry promising qualities closest to human hepatocytes in drug studies is a dream of many research laboratories. About 90% of drugs are metabolised by the liver. Therefore, most drug discovery studies utilise hepatocytes to understand the basic mechanism of the drug’s breakdown. To assure hepatocytes survival, various solvents were tested for their cytotoxicity on the cell line. Since most drugs are weakly soluble in water, they can be dissolved in an aprotic solvent. To obtain accurate results, the requirements of these solvents are biocompatible and non-toxic to the cells. One of the most commonly used solvents is dimethyl sulfoxide (DMSO). This study aims to understand the cell characteristic of cells doubling time and investigate the toxic effect of DMSO using the cell proliferation measurement technique. The toxicity was measured on liver-derived cell lines HepG2 and Huh-7. Cell growth and morphology were observed with an inverted phase microscope while cell viability was counted using Vi-Call XR 2.03. Results showed that a doubling time of 32 hours would be best for treatments on both cells. A concentration of more than 0.40% DMSO has significant toxicity and caused inhibition of proliferation on both cell lines, resulting in low cell count and higher cell death. Ethanol and methanol were observed as good solvents since they have low toxicity. However, drugs that were only dissolved in a low concentration of DMSO (0.05-0.2%) gave the best result without any harmful effect on cell proliferation.
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Bian, Xufei, Lan Jiang, Jing Zhou, Xiaoshu Guan, Jingyu Wang, Peng Xiang, Junyi Pan e Xiangnan Hu. "Improving Dissolution and Cytotoxicity by Forming Multidrug Crystals". Molecules 25, n.º 6 (16 de março de 2020): 1343. http://dx.doi.org/10.3390/molecules25061343.
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Both rosiglitazone and metformin have effects on blood glucose regulation and the proliferation of liver cancer cells. Combination therapy with these two drugs is common and effective for the treatment of diabetes in the clinic, however, the application of these two drugs is influenced by the poor dissolution of rosiglitazone and the gastrointestinal side-effect of metformin resulting from a high solubility. The formation of a multidrug crystal form (Rsg-Met) by a solvent evaporation method can solve the solubility issue. Crystal structure data and intramolecular hydrogen bonds were detected by X-ray diffraction and infrared spectroscopy. Surprisingly, Rsg-Met shortens the time spent in solubility equilibrium and multiplies the dissolution rate of Rsg. Finally, we found that a low concentration of Rsg-Met enhanced the proliferation inhibition effect on liver cancer cells (HepG2, SK-hep1) compared with rosiglitazone, without affecting the human normal cell line LO2.
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Sukhanov, D. S., E. D. Bazhanova e D. L. Teplyi. "ROLE OF HEPATOPROTECTORS AND IMMUNOMODULATORS IN REGULATION OF HEPATOCYTE APOPTOSIS INDUCED BY ANTITUBERCULOSIS TREATMENT". Annals of the Russian academy of medical sciences 68, n.º 8 (19 de agosto de 2013): 45–50. http://dx.doi.org/10.15690/vramn.v68i8.723.
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It was currently shown that hepatopathy due to drug toxicity is associated with increased apoptosis of hepatocytes. Therefore, development of drugs which regulate cell death is of great importance. Aim: to involve some hepatoprotectors (ademethionine, reamberin, remaxol) and immunomodulators (cycloferon) into regulation of apoptosis in experimental models of liver first-line antituberculousis drugs (isoniazid, rifampicin, pyrazinamide). Materials and methods: levels of apoptosis (TUNEL), expression of CD95 (receptor of tumor necrosis factor ― by immunohistochemistry), expression of caspase-8, caspase-3 and p53 (Western-blotting) were measured. Results: exposition of first-line antituberculousis drugs leads to dysthrophia of liver parenchyma cells with increased apoptosis of hepatocytes and activation of CD95, caspase-8 (external way) and overexpression of p53 and caspase-3. It was found that reamberin, cycloferon and remaxol have hepatoprotective effect improving liver histology; ademethionine administered by intraperitoneal injection showed no positive effects. Reamberin demonstrated apoptosis-inhibiting effect in the experiment whereas other drugs were found to be apoptosis inductors for hepatocytes in toxic hepatopathy. Conclusions: regulation of apoptosis by cycloferon and remaxol mediated by external and p53-dependent pathway is confirmed by increased expression of CD95 and p53 protein. Ademethionine might induce apoptosis by the intrinsic pathway.
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Chen, Wenzhuo, Xuefeng Li, Chengfei Liu, Jia He, Miao Qi, Yue Sun, Bingbing Shi et al. "β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells". Proceedings of the National Academy of Sciences 117, n.º 49 (23 de novembro de 2020): 30942–48. http://dx.doi.org/10.1073/pnas.2007798117.
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Despite the widespread clinical application of chemotherapeutic anticancer drugs, their adverse side effects and inefficient performances remain ongoing issues. A drug delivery system (DDS) designed for a specific cancer may therefore overcome the drawbacks of single chemotherapeutic drugs and provide precise and synergistical cancer treatment by introducing exclusive stimulus responsiveness and combined chemotherapy properties. Herein, we report the design and synthesis of a supramolecular drug delivery assembly 1 constructed by orthogonal self-assembly technique in aqueous media specifically for application in liver cancer therapy. Complex 1 incorporates the β-cyclodextrin host molecule-functionalized organoplatinum(II) metallacycle 2 with two specific stimulus-responsive motifs to the signaling molecule nitric oxide (NO), in addition to the three-armed polyethylene glycol (PEG) functionalized ferrocene 3 with redox responsiveness. With this molecular design, the particularly low critical aggregation concentration (CAC) of assembly 1 allowed encapsulation of the commercial anticancer drug doxorubicin (DOX). Controlled drug release was also achieved by morphological transfer via a sensitive response to the endogenous redox and NO stimuli, which are specifically related to the microenvironment of liver tumor cells. Upon combination of these properties with the anticancer ability from the platinum acceptor, in vitro studies demonstrated that DOX-loaded 1 is able to codeliver anticancer drugs and exhibit therapeutic effectiveness to liver tumor sites via a synergistic effect, thereby revealing a potential DDS platform for precise liver cancer therapeutics.
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Jing, Bolin, Gong Cheng, Jianjun Li, Zhuo A. Wang e Yuguang Du. "Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem". Marine Drugs 17, n.º 7 (13 de julho de 2019): 415. http://dx.doi.org/10.3390/md17070415.
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Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage(s) of tumor metastasis COS targeted. To study the inhibitory effects of a new partially acetylated chitooligosaccharide (paCOS) with fraction of acetylation (FA) 0.46 on each phase of liver cancer cell metastasis, a dynamic tumor-vessel microsystem undergoing physiological flow was leveraged. paCOS (FA = 0.46) significantly inhibited proliferation of HepG2 cells through vascular absorption on the chip, and inhibited migration of HepG2 cells by inhibiting the formation of pseudopod in liver tumor cells. It was also found that paCOS at 10 μg/mL had a stronger inhibitory effect on liver tumor cells invading blood vessels than that of paCOS at 100 μg/mL, and paCOS at 100 μg/mL, which had a significant destructive effect on tumor vascular growth and barrier function. Moreover, paCOS reduced the number of liver tumor cells adhering onto the surface of HUVECs layer after 3 h of treatment. Therefore, the results revealed that paCOS had considerable potential as drugs for anti-tumor metastasis.
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Medina-Pizaño, Mariana Yazmin, Marina Nayeli Medina-Rosales, Sandra Luz Martínez-Hernández, Liseth Rubi Aldaba-Muruato, José Roberto Macías-Pérez, Esperanza Sánchez-Alemán, Javier Ventura-Juárez e Martin Humberto Muñoz-Ortega. "Protective Effect of Curcumin against Doxazosin- and Carvedilol-Induced Oxidative Stress in HepG2 Cells". Oxidative Medicine and Cellular Longevity 2022 (11 de fevereiro de 2022): 1–15. http://dx.doi.org/10.1155/2022/6085515.
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Doxazosin and carvedilol have been evaluated as an alternative treatment against chronic liver lesions and for their possible role during the regeneration of damage caused by liver fibrosis in a hamster model. However, these drugs have been reported to induce morphological changes in hepatocytes, affecting the recovery of liver parenchyma. The effects of these α/𝛽 adrenoblockers on the viability of hepatocytes are unknown. Herein, we demonstrate the protective effect of curcumin against the possible side effects of doxazosin and carvedilol, drugs with proven antifibrotic activity. After pretreatment with 1 μM curcumin for 1 h, HepG2 cells were exposed to 0.1–25 μM doxazosin or carvedilol for 24, 48, and 72 h. Cell viability was assessed using the MTT assay and SYTOX green staining. Morphological changes were detected using the hematoxylin and eosin (H&E) staining and scanning electron microscopy (SEM). An expression of apoptotic and oxidative stress markers was analyzed using reverse transcription-quantitative PCR (RT-qPCR). The results indicate that doxazosin decreases cell viability in a time- and dose-dependent manner, whereas carvedilol increases cell proliferation; however, curcumin increases or maintains cell viability. SEM and H&E staining provided evidence that doxazosin and carvedilol induced morphological changes in HepG2 cells, and curcumin protected against these effects, maintaining the morphology in 90% of treated cells. Furthermore, curcumin positively regulated the expression of Nrf2, HO-1, and SOD1 mRNAs in cells treated with 0.1 and 0.5 μM doxazosin. Moreover, the Bcl-2/Bax ratio was higher in cells that were treated with curcumin before doxazosin or carvedilol. The present study demonstrates that curcumin controls doxazosin- and carvedilol-induced cytotoxicity and morphological changes in HepG2 cells possibly by overexpression of Nrf2.
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Yuhas, Yael, Eva Berent e Shai Ashkenazi. "Effect of Rifampin on Production of Inflammatory Mediators in HepG2 Liver Epithelial Cells". Antimicrobial Agents and Chemotherapy 55, n.º 12 (19 de setembro de 2011): 5541–46. http://dx.doi.org/10.1128/aac.05149-11.
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ABSTRACTRifampin, a potent antibacterial agent, is one of the main drugs used in the treatment of mycobacterial infections. Hepatotoxicity is a well-documented adverse event. The aim of this study was to investigate the effect of rifampin on the production of inflammatory mediators in human epithelial HepG2 liver cells in the absence or presence of proinflammatory cytokines. Incubation of HepG2 cells with a cytokine mix plus rifampin was associated with a significant dose-dependent increase in the production of nitric oxide compared to incubation with the cytokine mix alone (P< 0.05) as well as with an increase in inducible nitric oxide synthase protein and mRNA expression. Rifampin significantly increased the secretion of interleukin 8 (IL-8) in both untreated cells (P< 0.001) and cytokine-treated cells (P< 0.006). An array screening assay revealed that rifampin stimulated the production of IL-1β and gamma interferon-induced protein-10 (IP-10) in untreated cells and increased the secretion of RANTES in cytokine-treated cells. Together, these results indicate that rifampin may exert proinflammatory effects on liver cells.
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Coelho, DR, ACAX De-Oliveira, TEM Parente, BS Leal, LF das Chagas, TN Oliveira, TD Saint’Pierre e FJR Paumgartten. "In vivo and in vitro effects of pentavalent antimony on mouse liver cytochrome P450s". Human & Experimental Toxicology 36, n.º 1 (11 de julho de 2016): 33–41. http://dx.doi.org/10.1177/0960327116637110.
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Pentavalent antimonial (Sb5+) drugs such as meglumine antimoniate (MA) are the mainstay treatment of leishmaniases in developing countries. The effects of these compounds on drug-metabolizing enzymes have not been characterized and their potential pharmacokinetic interactions with other drugs are therefore unknown. The present study investigated whether treatment with MA (300 mg Sb5+/kg body weight/day, subcutaneously) for 24 days affected the activities of cytochrome P450 (CYP)1A (ethoxyresorufin- O-deethylase), CYP2A5 (coumarin 7-hydroxylase), CYP2E1 ( p-nitrophenol-hydroxylase), CYP2B9/10 (benzyloxy-resorufin- O-debenzylase), or CYP3A11 (erythromycin- N-demethylase) in the livers of Swiss Webster (SW) and DBA-2 male and female mice. The results showed that CYP2A5-, CYP2E1-, and CYP3A11-catalyzed reactions were unaffected by MA treatment. A decrease in CYP2B9/10 activity was noted in DBA-2 females (but not males) and was not observed in SW males or females. However, repeated MA administration reduced mouse liver CYP1A activity. CYP1A2 messenger RNA (mRNA) levels were not affected by MA and in vitro exposure of mouse liver microsomes to Sb3+ and Sb5+ did not reduce CYP1A activity. These findings suggested that in vivo treatment with Sb5+ drugs depressed CYP1A activity, without downregulating CYP1A2 mRNA expression. Since in vitro treatment of liver microsomes failed to inhibit CYP1A activity, this effect may require intact cells.
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Horita, Yasuhiro, e Norio Doi. "Comparative Study of the Effects of Antituberculosis Drugs and Antiretroviral Drugs on Cytochrome P450 3A4 and P-Glycoprotein". Antimicrobial Agents and Chemotherapy 58, n.º 6 (24 de março de 2014): 3168–76. http://dx.doi.org/10.1128/aac.02278-13.
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ABSTRACTPredicting drug-drug interactions (DDIs) related to cytochrome P450 (CYP), such as CYP3A4 and one of the major drug transporters, P-glycoprotein (P-gp), is crucial in the development of future chemotherapeutic regimens to treat tuberculosis (TB) and TB/AIDS coinfection cases. We evaluated the effects of 30 anti-TB drugs, novel candidates, macrolides, and representative antiretroviral drugs on human CYP3A4 activity using a commercially available screening kit for CYP3A4 inhibitors and a human hepatocyte, HepaRG. Moreover, in order to estimate the interactions of these drugs with human P-gp, screening for substrates was performed. For some substrates, P-gp inhibition tests were carried out using P-gp-expressing MDCK cells. As a result, almost all the compounds showed the expected effects on human CYP3A4 both in thein vitroscreening and in HepaRG cells. Importantly, the unproven mechanisms of DDIs caused by WHO group 5 drugs, thioamides, andp-aminosalicylic acid were elucidated. Intriguingly, clofazimine (CFZ) exhibited weak inductive effects on CYP3A4 at >0.25 μM in HepaRG cells, while an inhibitory effect was observed at 1.69 μM in thein vitroscreening, suggesting that CFZ autoinduces CYP3A4 in the human liver. Our method, based on one of the pharmacokinetics parameters in humans, provides more practical information associated with not only DDIs but also with drug metabolism.
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Noguchi, T., H. Fukumoto, Y. Mishina e M. Obinata. "Differentiation of erythroid progenitor (CFU-E) cells from mouse fetal liver cells and murine erythroleukemia (TSA8) cells without proliferation". Molecular and Cellular Biology 8, n.º 6 (junho de 1988): 2604–9. http://dx.doi.org/10.1128/mcb.8.6.2604-2609.1988.
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Erythropoietin (epo) appears to play a significant role in influencing the proliferation and differentiation of erythroid progenitor (CFU-E) cells. To determine the mechanism of action of epo, the effect of drugs on the in vitro colony formation of CFU-E cells induced from a novel murine erythroleukemia cell line, TSA8, was examined. While cytosine arabinoside inhibited colony formation and terminal differentiation of the CFU-E cells responding to epo, herbimycin, which is a drug that inhibits src-related phosphorylation, inhibited colony formation only. The same effect of herbimycin was observed with normal CFU-E cells from mouse fetal liver cells. These results suggest that epo induces two signals, one for proliferation and the other for differentiation, and that the two signals are not linked in erythroid progenitor cells.
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Noguchi, T., H. Fukumoto, Y. Mishina e M. Obinata. "Differentiation of erythroid progenitor (CFU-E) cells from mouse fetal liver cells and murine erythroleukemia (TSA8) cells without proliferation." Molecular and Cellular Biology 8, n.º 6 (junho de 1988): 2604–9. http://dx.doi.org/10.1128/mcb.8.6.2604.
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Erythropoietin (epo) appears to play a significant role in influencing the proliferation and differentiation of erythroid progenitor (CFU-E) cells. To determine the mechanism of action of epo, the effect of drugs on the in vitro colony formation of CFU-E cells induced from a novel murine erythroleukemia cell line, TSA8, was examined. While cytosine arabinoside inhibited colony formation and terminal differentiation of the CFU-E cells responding to epo, herbimycin, which is a drug that inhibits src-related phosphorylation, inhibited colony formation only. The same effect of herbimycin was observed with normal CFU-E cells from mouse fetal liver cells. These results suggest that epo induces two signals, one for proliferation and the other for differentiation, and that the two signals are not linked in erythroid progenitor cells.
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Mo, Jiantao, Xuanbo Da, Qiaoxin Li, Jingjing Huang, Le Lu e Hongwei Lu. "The Study of Exosomes-Encapsulated mPEG-PLGA Polymer Drug-Loaded Particles for Targeted Therapy of Liver Cancer". Journal of Oncology 2022 (17 de setembro de 2022): 1–10. http://dx.doi.org/10.1155/2022/4234116.
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The emergence of targeted drugs brings hope to patients with advanced liver cancer. However, due to the complex and diverse environment in the human body, the overall response rate of targeted drugs is not high. Therefore, how to efficiently deliver targeted drugs to tumor sites is a major challenge for current research. The project intends to construct mPEG-PLGA nanoparticles loaded with Sora and encapsulate them with exosomes for targeted therapy of hepatocellular carcinoma. mPEG-PLGA drug-loaded nanoparticles were prepared by the dialysis method and characterized by TEM and DLS. The obtained nanoparticles were incubated with the exosomes of liver cancer cells, and the exosomes-encapsulated drug-loaded nanoparticles (Exo-Sora-NPs) were obtained under pulsed ultrasound conditions, and they were characterized by Western blot, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The toxic effect of Exo-Sora-NPs on liver cancer cells was detected by the CCK-8 experiment. The uptake efficiency of nanoparticles by liver cancer cells was detected by a confocal microscope. The accumulation and infiltration depth of nanomedicine in liver cancer tissues were observed by confocal microscope on frozen sections of liver cancer tissue after the H22 liver cancer subcutaneous tumor transplantation model was constructed. The tumor size, body weight, pathology, and serology analysis of mice were measured after administration. The mPEG-PLGA polymer drug-loaded particles encapsulated by exosomes have high targeting ability and biosafety. To a certain extent, they can target the drug to the tumor site with a smaller systemic response and have a highly effective killing effect on the tumor. Nanodrug-loaded particles encapsulated by exosomes have great potential as drug carriers.
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Wang, Meixi, Jianrui Li, Hu Li, Biao Dong, Jing Jiang, Nannan Liu, Jiali Tan et al. "Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease". International Journal of Molecular Sciences 23, n.º 10 (16 de maio de 2022): 5544. http://dx.doi.org/10.3390/ijms23105544.
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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and there is no specific drug to treat it. Recent results showed that 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) is associated with liver diseases, but these conclusions are controversial. Here, we showed that HSD17B13 was more highly expressed in the livers of NAFLD patients, and high expression was induced in the livers of murine NAFLD models and cultural hepatocytes treated using various etiologies. The high HSD17B13 expression in the hepatocytes facilitated the progression of NAFLD by directly stabilizing the intracellular lipid drops and by indirectly activating hepatic stellate cells. When HSD17B13 was overexpressed in the liver, it aggravated liver steatosis and fibrosis in mice fed with a high-fat diet, while down-regulated the high expression of HSD17B13 by short hairpin RNAs produced a therapeutic effect in the NAFLD mice. We concluded that high HSD17B13 expression is a good target for the development of drugs to treat NAFLD.
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Anju, Thangammal, Radhakrishnan Preetha, Raja Shunmugam, Shivshankar R. Mane, Jesu Arockiaraj e Shivasekar Ganapathy. "Non-Clinical Investigation of Tuberculosis Drugs: Conjugated Norbornene- Based Nanocarriers Toxic Impacts on Zebrafish". Current Nanomedicine 11, n.º 4 (dezembro de 2021): 224–36. http://dx.doi.org/10.2174/2468187312666211221130125.
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INTRODUCTION: Rifampicin conjugated (R-CP), and rifampicin -isoniazid dual conjugated (RI-CP) norbornene-derived nanocarriers are newly designed for pH stimuli-responsive delivery of tuberculosis (TB) drugs. Its biosafety level is yet to be well established. OBJECTIVES: To assess the impacts of the nanocarriers on liver cells using zebrafish animal model and human liver cell line model (HepG2). METHODS: Initially, lethal dose concentration for the norbornene-derived nanocarrier systems in zebrafish was determined. The toxic effects were analysed at the sub-lethal drug concentration by histopathological study, total GSH level, gene expression and DNA damage in zebrafish liver cells. Fish erythrocyte nuclear abnormalities were also evaluated. Cell viability and oxidative stress level (ROS generation) after exposure to the nanoconjugates was determined using HepG2 cell in the in vitro study. RESULTS: In vivo studies of both R-CP and RI-CP showed 100% mortality at 96 hours for exposure concentration >100mg/l and showed toxic changes in zebrafish liver histology, GSH, and DNA damage levels. A noticeable upregulated PXR, CYP3A and cyp2p6 genes was observed in RI-CP exposure than in RIF or R-CP molecules. The in vitro study revealed a dose-dependent effect on cell viability and ROS generation for RIF, R-CP and RI-CP exposures in HepG2 cells. CONCLUSION: The current study reports that the rifampicin conjugated (R-CP) and rifampicin-isoniazid conjugated (RI-CP) norbornene derived nanocarriers exhibit enhanced toxic responses in both adult zebrafish and HepG2 cells. The pH-sensitive norbornene derived nanocarriers on conjugation with different drugs exhibited varied impacts on hepatic cells. Hence the present investigation recommends a complete metabolomics analysis and norbornene carrier-drug interaction study to be performed for each drug conjugated norbornene nanocarrier to ensure its biosafety.
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Wu, Yafeng, Run Ma, Cuizhen Long, Yuanhui Shu, Ping He, Yan Zhou, Yining Xiang e Yuping Wang. "The protective effect of cannabinoid type II receptor agonist AM1241 on ConA-induced liver injury in mice via mitogen-activated protein kinase signalling pathway". International Journal of Immunopathology and Pharmacology 35 (janeiro de 2021): 205873842110352. http://dx.doi.org/10.1177/20587384211035251.
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Introduction The endocannabinoid system plays an important role in regulating the immune responses in inflammation. At present, there are no good clinical drugs for many immune liver diseases. Methods We explored the protective effect of the cannabinoid type II (CB2) receptor agonist AM1241 on the liver of mice with acute liver injury caused by concanavalin from the perspective of inflammation and immunity. Pathological evaluation in hepatic tissue was examined by haematoxylin and eosin (HE) staining and the levels of biochemical parameters in the serum were measured by automatic biochemical analysis. The content of inflammatory factors was measured by enzyme-linked immunosorbent assay and real-time quantitative reverse transcription polymerase chain reaction (real-time PCR). The liver apoptosis-related proteins were observed by immunohistochemistry. The expression of liver injury-related proteins was analysed by Western blot. Immune cells were isolated from the liver of mice and studied in vitro. Results Reduced levels of alanine transaminase and aspartate transaminase were observed in ConA-induced liver injury mice treated with AM1241, together with attenuated liver damage evidenced by H&E staining. Moreover, AM1241 inhibited the protein and gene expression levels of TNF-α, IL-6 and IFN-γ in the livers of mice. The phosphorylation levels of p38, JNK, ERK1/2, P65 and cAMP response element-binding protein (CREB) in the mouse were significantly reduced in AM1241 pretreatment, while the level of p-JNK increased. In addition, the P/T-P65 and P/T-CREB of the AM1241 pretreatment group were significantly reduced. The results of immunohistochemistry measurement are consistent with those of Western blotting. The CB2-mediated effect is through macrophage-like Kupffer cells. Conclusion Our study suggests that the ConA-induced liver injury model in mice is protected by CB2 agonist AM1241 by modulation of CB2 receptor-rich immune cells, for example, Kupffer cells. Reduced inflammatory responses regulate apoptosis/cell death in the liver particularly hepatocytes and other parenchymal cells.
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Ruoß, Marc, Silas Rebholz, Marina Weimer, Carl Grom-Baumgarten, Kiriaki Athanasopulu, Ralf Kemkemer, Hanno Käß, Sabrina Ehnert e Andreas K. Nussler. "Development of Scaffolds with Adjusted Stiffness for Mimicking Disease-Related Alterations of Liver Rigidity". Journal of Functional Biomaterials 11, n.º 1 (14 de março de 2020): 17. http://dx.doi.org/10.3390/jfb11010017.
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Drug-induced liver toxicity is one of the most common reasons for the failure of drugs in clinical trials and frequent withdrawal from the market. Reasons for such failures include the low predictive power of in vivo studies, that is mainly caused by metabolic differences between humans and animals, and intraspecific variances. In addition to factors such as age and genetic background, changes in drug metabolism can also be caused by disease-related changes in the liver. Such metabolic changes have also been observed in clinical settings, for example, in association with a change in liver stiffness, a major characteristic of an altered fibrotic liver. For mimicking these changes in an in vitro model, this study aimed to develop scaffolds that represent the rigidity of healthy and fibrotic liver tissue. We observed that liver cells plated on scaffolds representing the stiffness of healthy livers showed a higher metabolic activity compared to cells plated on stiffer scaffolds. Additionally, we detected a positive effect of a scaffold pre-coated with fetal calf serum (FCS)-containing media. This pre-incubation resulted in increased cell adherence during cell seeding onto the scaffolds. In summary, we developed a scaffold-based 3D model that mimics liver stiffness-dependent changes in drug metabolism that may more easily predict drug interaction in diseased livers.
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Irshad, Faiza, Kanwal Saeed, Muhammad Adeel Qama, Jamshad Latif, Zia Ul Mustafa e Lubaba Mukhtar. "Histological alterations in Rabbit liver after treatment with dexamethasone". Pakistan Journal of Medical and Health Sciences 15, n.º 9 (30 de setembro de 2021): 2373–75. http://dx.doi.org/10.53350/pjmhs211592373.
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Background One of the most potent glucocorticoids is known as Dexamethasone. Many metabolic side effect shave been reported on almost every organ after dexamethasone treatment specially its effect on liver. Aim: To investigate harmful side effects of dexamethasone sodium phosphate on rabbit’s liver that serve as human liver model via using light microscope, by administration of two doses (extreme) and two durations in order to depict the duration as well as dosage dependency. Methods: Liver samples were taken via rabbits who were administered dexamethasone sodium phosphate. Then two Stratas were made namely, 1 and 2. The fixations of liver samples were carried out and underwent into evaluation in order to observe any histochemical and histological alterations. Study duration is from February to May 2021 Rabbits were brought from Veterinary Research Institute, Lahore. These Rabbits were kept in cages in the animal house of PGMI, Bird wood road Lahore. Results: The ballooning and vacuolation of hepatic cells were seen in the liver in case of Stratas that were treated along with the degenerative alterations of these cells, congestion and dilatation of central hepatic vein with sinusoidal capillaries, positive periodic acid schiff's stain (PAS) reactions. The severity of all these alterations was dependent upon duration and dosage. Conclusion: Morphological variations induced in the liver by dexamethasone sodium phosphate could be accepted as side effects of these drugs. Keywords: Liver, dexamethasone, histology, glycogen.
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Komala M, Sathesh Kumar S e Padmavathy J. "Novel Drug Formulation for the Treatment of Hepatic Cancer- A Review". International Journal of Research in Pharmaceutical Sciences 11, n.º 3 (29 de julho de 2020): 4395–401. http://dx.doi.org/10.26452/ijrps.v11i3.2658.
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For metabolic transformation, uptake, detoxification, and excretion liver is the primary organ that is highly equipped. Thus, the liver requires targeting by means like a carrier-mediated mechanism to take xenobiotics into the bile, though high hepatic concentration is achieved by most of the drugs. Thus resulting in high first-pass metabolism displayed by the drugs and thus resulting in rapid clearance of the drugs. Uptake of particulate materials is highly contributed by the kupffer cells largely. However, drug uptake by the liver is highly dependent on hepatocytes. In drug delivery, tissue engineering and regenerative medicines which are various biomedical applications construction of nanoscale based bioactive materials is a desirable approach of self-assembly. By using a targeting moiety, we can decrease the side effects of the drug and increases the therapeutic effect of the drug. Lipoproteins are potential drug carrier to target the organs. Lipoproteins consist of cholesterol, polar lipid core surrounding phospholipid monolayer and apoproteins are embedded in it, and these lipoproteins are spherical. The core is a polar lipid in nature so that highly hydrophobic drugs are easily incorporated into the core. Lipoproteins are completely non-immunogenic, biodegradable nature. The present review should be regularly inspected to beat into the global market at an affordable price as well, particularly the vehicles which are proven to be efficacious in drug delivery systems used to treat liver diseases like cancer.
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Smok, A. M., A. M. Malkova, D. A. Kudlay e A. A. Starshinova. "Possibilities for correcting hepatotoxic reactions during therapy in patients with COVID-19 (case report)". Translational Medicine 7, n.º 6 (18 de dezembro de 2020): 65–72. http://dx.doi.org/10.18705/2311-4495-2020-7-6-65-72.
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In 2020, a pandemic of the new coronavirus infection (COVID-19) began. Treatment of this infection is limited by the lack of effective etiological treatment, which requires the selection of empirical and symptomatic therapy. The obtained some effectiveness of the use of antimalarial drugs, antiretroviral drugs in combination with antibacterial therapy made it possible to recommend it for use in the treatment regimen for patients with COVID-19. However, these drugs provoke the development of undesirable side reactions that require correction to continue treatment. Considering the need to use complex therapy in the treatment of patients with COVID-19 and the direct effect of the virus on liver cells, the likelihood of developing hepatotoxicity is quite high. The described cases of liver damage are characterized by impaired functional activity, an increase in the level of liver function tests, the development of small-drop fatty infiltration and a mild inflammatory reaction in the liver lobules. The development of these complications requires the hepatoprotective drugs, which increase the liver’s resistance to the damaging effects of various pathogens and help restore the functional activity of hepatocytes. According to the conducted studies, hepatotropic drug inosine+ + meglumine + methionine + nicotinamide + succinic acid and reamberin contribute to the normalization of lipid metabolism, a decrease in the level of enzyme markers of liver damage. The article presents the complex treatment with lopinavir + ritonavir. Thanks to hepatoprotective therapy, a week later, a decrease in ALT, alpha-amylase, blood counts to normal values was achieved.
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Akın, Bakır, Ökçesiz e Eken. "Evaluation of Cytotoxic Effects of Carnosic Acid Alone and Combination with Cisplatin in HepG2 Cells". Proceedings 40, n.º 1 (31 de dezembro de 2019): 39. http://dx.doi.org/10.3390/proceedings2019040039.
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Natural products are important in prevention and treatment of cancer because of their antitumor effect and reducing side effects of chemotherapeutic drugs. The aim of this study was to investigate the potential cytotoxic effecs of carnosic acid and in combination with cisplatin in liver cancer cells. Cytotoxicity was assessed using MTT assay for 24/48 hours. The intracellular ROS levels were determined using the oxidation‐sensitive fluorescent probes DCFH‐DA. Changes in the mitochondrial membrane potential (MMP) were detected using JC-1 commercial kit. Concentrations were selected for carnosic acid and cisplatin according to IC50 values. As a results, % cell viability decreased with concentration/time dependent and combination treatments showed potentiated effect at 48 hours exposure. According to DCFH-DA assay, it was observed that carnosic acid and combinations with cisplatin reduced intracellular ROS levels in presence of H2O2. Carnosic acid and its combinations reduced MMP. Our results showed that carnosic acid has the potential to inhibit growth in HepG2 cells without increasing ROS production. In conclusion, carnosic acid alone and combination with cisplatin may be promising for the prevention and treatment of liver cancer.
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Su, Qiang, Wei Kuang, Weiyi Hao, Jing Liang, Liang Wu, Chunmei Tang, Yali Wang e Tao Liu. "Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes". Mediators of Inflammation 2021 (19 de fevereiro de 2021): 1–13. http://dx.doi.org/10.1155/2021/8086253.
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Patients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NLRP3-inflammasome inhibitors (INF39 and CP-456773) or NLRP3 siRNA. Histopathological changes that occurred in liver tissue were examined by H&E staining. Additionally, the levels IL-33, IL-18, IL-1β, NLRP3, ASC, and cleaved-caspase 1 expression in the liver tissues were also determined. NAT2 and CYP2E1 expression were identified by QRT-PCR analysis. Finally, in vitro assays were performed to examine the effects of siRNA targeting NLRP3. Treatment with the antituberculosis drugs caused significant liver injuries, induced inflammatory responses and oxidative stress (OS), activated NLRP3 inflammasomes, reduced the activity of drug-metabolizing enzymes, and altered the antioxidant defense system in rats and hepatic cells. The NLRP3 inflammasome was required for INH- and RIF-induced liver injuries that were produced by inflammatory responses, OS, the antioxidant defense system, and drug-metabolizing enzymes. This study indicated that the NLRP3 inflammasome is involved in antituberculosis drug-induced liver injuries (ATLIs) and suggests NLRP3 as a potential target for attenuating the inflammation response in ATLIs.
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Abolhasani, Ahmad, Fatemeh Heidari, Somayeh Noori, Shokoufeh Mousavi e Hoda Abolhasani. "Cytotoxicity Evaluation of Dimethoxy and Trimethoxy Indanonic Spiroisoxazolines Against Cancerous Liver Cells". Current Chemical Biology 14, n.º 1 (26 de maio de 2020): 38–47. http://dx.doi.org/10.2174/2212796813666190926112807.
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Background: 3'-(3,4-dimethoxyphenyl)-4'-(4-(methylsulfonyl)phenyl)-4'H-spiro [indene-2,5'-isoxazol]-1(3H)-one and 4'-(4-(methylsulfonyl)phenyl)-3'-(3,4,5-trimethoxyphenyl)- 4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one compounds containing indanonic spiroisoxazoline core are widely known for their antiproliferative activities and investigation of tubulin binding modes. Objective: To evaluate the cytotoxicity effect of Dimethoxy and Trimethoxy Indanonic Spiroisoxazolines against HepG2 cancerous liver cell line and to perform a comparison with other known anti-liver cancer drugs. Methods: The evaluation of cytotoxicity of dimethoxy and trimethoxy indanonic spiroisoxazoline compounds, Oxaliplatin, Doxorubicin, 5-fluorouracil and Cisplatin against HepG2 (hepatocellular liver carcinoma) cell line has been performed using MTT assay and analyzed by GraphPad PRISM software (version 8.0.2). Results: Potent cytotoxicity effects against HepG2 cell line, comparable to Cisplatin (IC50= 0.047±0.0045 µM), Oxaliplatin (IC50= 0.0051µM), Doxorubicin (IC50= 0.0014µM) and 5- fluorouracil (IC50= 0.0089 µM), were shown by both dimethoxy (IC50= 0.059±0.012 µM) and trimethoxy (IC50= 0.086±0.019 µM) indanonic spiroisoxazoline compounds. Conclusion: In vitro biological evaluations revealed that dimethoxy and trimethoxy indanonic spiroisoxazoline compounds are good candidates for the development of new anti-liver cancer agents.
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ÖZGERMEN, Başak, Orhan YAVUZ e Ali Evren HAYDARDEDEOĞLU. "Investigation of the effects of mesenchymal stem cell administration on liver recovery in experimental hepatotoxicity model". Journal of Advances in VetBio Science and Techniques 7, n.º 2 (31 de agosto de 2022): 185–93. http://dx.doi.org/10.31797/vetbio.1029373.
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Hepatotoxicity refers to liver dysfunction associated with certain medical drugs and chemicals. Studies have shown that mesenchymal stem cells have a positive effect on the improvement of liver diseases. The aim of this study was to investigate the potential protective effects of fetal kidney-induced mesenchymal stem cells on Doxorubicin-induced hepatotoxicity in rats. Sprague dawley rats were divided into three groups as control, sham, and treatment group. Intraperitoneal mesenchymal stem cells were treated with BrdU prior to transplantation so that they could be followed up after invivo transplantation. After completion of the experimental steps, the groups were monitored for 5 weeks. Then the rats were terminated and their livers were taken for histopathological and immunohistochemical evaluation. In immunohistochemical examinations performed with TNF-α, Caspase-3 and COX-2 primary antibodies, the most severe positivity was in the sham group, followed by the control and treatment groups. While the control and sham groups were found to be statistically similar in immunohistochemical staining with anti-BrdU antibody, the treatment group was found to be significantly different from the other groups (p<0.05). As a result, it has been revealed that mesenchymal stem cells administered intraperitoneally to rats with Doxorubicin-induced hepatotoxicity, prevent degeneration and necrosis in hepatocytes, and TNF-α, COX-2, and Caspase-3 levels were significantly decreased immunohistochemically, proving increased liver regeneration.
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Ali Labib, Heba M. "Modification of alprazolam-induced liver injury by bone marrow-derived mesenchymal stem cells and the role of miRNA-192". European Journal of Anatomy 26, n.º 6 (novembro de 2022): 615–33. http://dx.doi.org/10.52083/ivll6465.
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The group of drugs known as Benzodiazepines (BDZs) are among the most widely prescribed CNS-depressant drugs. Alprazolam (Alp) is a member of the BDZs family, commonly prescribed as an antipsychotic and anxiolytic agent. Induction of oxidative stress, impairment of cognitive functions and psychomotor skills, conformational alterations in hemoglobin structure and elevation of liver enzymes are among the side effects reported on the use of alprazolam. Several studies have found that alprazolam could favor hepatotoxicity, whereas other studies contradicted those findings. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been studied as a novel approach for treatment of liver diseases. The current study was designed to assess the biochemical, histopathological and molecular liver alterations in response to oral administration of alprazolam at a dose of 0.3 mg/kg/day for 4 weeks in adult male albino rats and to evaluate the therapeutic effect of BM-MSCs on the alprazolam- induced alterations. Forty adult male albino rats (Sprague Dawley strain; 170-200 g mean body weight) were used. Liver enzymes were measured, isolation and preparation of BM- MSCs were done, and immunohistochemical staining for alpha smooth muscle actin and FGF2 were assessed. Moreover, histological and ultrastructural liver tissue examination and PCR detection of SOD, TNF-α and mirNA-192 were investigated. Animals exposed to alprazolam developed liver injury characterized by significant increase in TNF-α and significant decrease in SOD and miRNA- 192 expression. Histological findings provided supportive evidence for the biochemical and molecular analyses. Treatment with stem cells caused a significant alleviation of the alprazolam- induced findings. In conclusion, alprazolam was found to induce liver injury and oxidative stress, which were ameliorated by BM-MSCs administration.
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Zarrinpar, Ali. "Metabolic Pathway Inhibition in Liver Cancer". SLAS TECHNOLOGY: Translating Life Sciences Innovation 22, n.º 3 (17 de março de 2017): 237–44. http://dx.doi.org/10.1177/2472630317698683.
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Liver cancer is fundamentally physiologically different from the surrounding liver tissue. Despite multiple efforts to target the altered signaling pathways created by oncogenic mutations, not many have focused on targeting the altered metabolism that allows liver cancer to develop and grow. Still to be resolved is the question of whether the altered metabolic pathways in this cancer differ enough from the surrounding noncancerous cells to allow for the development of potent and specific compounds. Clinical studies of metabolic modulators would provide some more information with regard to the feasibility of this approach. Furthermore, as it appears that oncogenic signaling is essential to this cancer’s altered metabolism, it stands to reason that targeting this altered signaling may allow the exploitation of specific metabolic vulnerabilities in combination with other drugs for enhanced efficacy. The identification of biomarkers of metabolic sensitivity will also be essential to determine whether these drugs will have the desired effect.
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Teixeira, Sarah Fernandes, Isabella dos Santos Guimarães, Klesia Pirola Madeira, Renata Dalmaschio Daltoé, Ian Victor Silva e Leticia Batista Azevedo Rangel. "Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells". Jornal Brasileiro de Pneumologia 39, n.º 6 (dezembro de 2013): 644–49. http://dx.doi.org/10.1590/s1806-37132013000600002.
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OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.
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Domnina, L. V., J. A. Rovensky, J. M. Vasiliev e I. M. Gelfand. "Effect of microtubule-destroying drugs on the spreading and shape of cultured epithelial cells". Journal of Cell Science 74, n.º 1 (1 de março de 1985): 267–82. http://dx.doi.org/10.1242/jcs.74.1.267.
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The role of microtubules in the spreading of cells from the liver-derived IAR2 rat cell line was studied. Cells in the control medium seeded on a flat isotropic glass surface rapidly spread to form discoid shapes. Spreading in colcemid-containing medium was disorganized and delayed; partial reversal of spreading was observed. Nevertheless, even in the presence of colcemid the cells finally spread to discoid flattened shapes. IAR2 cells in medium without colcemid spread not to discoid but to elongated shapes under three different sets of conditions: (1) when the cells were forced to spread on narrow strips of adhesive glass surface between two non-adhesive lipid films; (2) when the cells spread on the poorly adhesive surface of poly(HEMA)-covered glass; (3) when the cells spread on the usual glass surfaces in medium containing cytochalasin D. Addition of colcemid to the media reversed the polarized spreading under the first two conditions; colcemid did not reverse the formation of the elongated cell shape acquired by the cells spreading in cytochalasin-containing medium. Effects of microtubule-destroying drugs on the spreading of epithelial and fibroblast cells are compared and discussed. It is suggested that microtubules are essential for the stabilization of the spread state of those attached cytoplasmic processes and lamellae that do not have numerous and stable-cell substratum contacts, e.g. the processes formed at the early stages of spreading or the elongated processes of polarized cells. Possibly, microtubules stabilize the non-contracted state of the actin cytoskeleton in these processes.
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Chen, Zhiliang, Tony C. H. Chow, Shicong Wang, Gigi C. T. Leung, Sharon L. Y. Wu e David T. Yew. "Reaction of the Liver upon Long-Term Treatment of Fluoxetine and Atorvastatin Compared with Alcohol in a Mouse Model". Journal of Toxicology 2021 (30 de dezembro de 2021): 1–8. http://dx.doi.org/10.1155/2021/9974969.
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Background. Alcoholism is known to cause liver toxicity and is extensively researched. On the other hand, stress, depression, and obesity are interrelated conditions with alcoholism, and their medications would affect the liver itself. In this study, we investigated the effects of the drugs fluoxetine and atorvastatin on the liver and compared with those of alcohol in a mouse model. Methods. Comparisons of animals treated with the three drugs were carried out: serum aspartate transaminase (AST), alanine transaminase (ALT), and albumin were measured; liver tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta-1) levels were evaluated; proliferative cells were detected via immunohistochemistry (IHC) targeting on proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2); for apoptosis, IHC targeting on activated caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were employed; and histopathology was also documented in all groups. Results. For ALT, AST, albumin, and liver TNF alpha, only the ethanol group surged to significantly higher levels. For TGF beta-1, both ethanol and atorvastatin groups reached a significantly higher level. PCNA and MCM2 showed increased proliferation in the livers of all three groups, with the ethanol group having the highest number of positive cells followed by atorvastatin and then the fluoxetine group. As for cell death, both ethanol and fluoxetine groups showed significantly more apoptosis than control in TUNEL and activated caspase-3, while in the atorvastatin group, activated caspase-3 positive cells increased significantly, but the increase in TUNEL-positive cells did not reach statistical significance.
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Lin, Chun-Ching, Jer-Min Lin e Hui-Fen Chiu. "Studies on Folk Medicine "Thang-kau-tin" from Taiwan (I) The Anti-inflammatory and Liver-protective Effect". American Journal of Chinese Medicine 20, n.º 01 (janeiro de 1992): 37–50. http://dx.doi.org/10.1142/s0192415x92000059.
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Five species of crude drugs are used as "Thang-kau-tin" on Taiwan market: (1) the stem of Mallotus repandus (Willd.) Muell. -Arg, (2) the stem and root of M. repandus (Willd.) Muell. -Arg, (3) the stem of Bauhinia championii Benth, (4) the stem with hooks of Uncaria hirsuta Haviland and (5) the stem with hooks of U. rhynchophylla Miquel. To clarify the effect of these crude drugs as anti-inflammatory and liver-protective agents, studies were conducted on water extracts of these five crude drugs. The statistical analysis (ANOVA) indicated that the stem of M. repandus showed the best anti-inflammatory activity against the paw edema induced by carrageenan. Nevertheless, the acute increase of GOT and GPT levels caused by CCl 4 were markedly decreased by the treatment of M. repandus (stem), B. championii and U. hirsuta as a recipe group. The pathological changes around the central vein including fatty change, ballooning degeneration, cell necrosis, the increase in lymphocytes and Kupffer cells were improved by the treatment with the group of crude drugs as mentioned above.
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Zheng, Rendong, Kemian Liu, Kun Chen, Wen Cao, Lin Cao, Huifeng Zhang, Hongping Sun e Chao Liu. "Lithium Carbonate in the Treatment of Graves’ Disease with ATD-Induced Hepatic Injury or Leukopenia". International Journal of Endocrinology 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/694023.
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Objective. GD with ATD-induced hepatic injury or leukopenia occurs frequently in clinical practice. The purpose of the present study was to observe the clinical effect of lithium carbonate on hyperthyroidism in patients with GD with hepatic injury or leukopenia.Methods. Fifty-one patients with GD with hepatic injury or leukopenia participated in the study. All patients were treated with lithium carbonate, in addition to hepatoprotective drugs or drugs that increase white blood cell count. Thyroid function, liver function, and white blood cells were measured. Clinical outcomes were observed after a 1-year follow-up.Results. After treatment for 36 weeks, symptoms of hyperthyroidism and the level of thyroid hormones were improved and liver function, and white blood cells returned to a normal level. Twelve patients (23.5%) obtained clinical remission, 6 patients (11.8%) relapsed after withdrawal, 25 patients (49.0%) received radioiodine therapy, and 8 patients (15.7%) underwent surgical procedures after lithium carbonate treatment.Conclusion. Lithium carbonate has effects on the treatment of mild-to-moderate hyperthyroidism caused by GD, and it is particularly suitable for patients with ATD-induced hepatic injury or leukopenia.
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Baothman, Othman, Bhaa Nagaty, Mazin Zamzami e Hasan Al-Talhi. "In vivo protective effect of cinnamon aqueous extract in carbon tetrachloride-treated male albino rats". Acta Scientiarum. Health Sciences 43 (13 de outubro de 2021): e52826. http://dx.doi.org/10.4025/actascihealthsci.v43i1.52826.
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The liver as an organ is important for the metabolism of drugs and toxins. However, it is not immune from environmental insults. Exposure of liver cells to carbon tetrachloride (CCl4) results in the generation of tricholoromethyl radicals, which induce liver toxicity. This study aims at investigating the ameliorative effect of the cinnamon aqueous extract (CAE) against CCl4-induced hepatotoxicity in male albino rats. Hepatotoxicity was induced in rats through the intraperitoneal administration of 0.5 mL kg-1 body weight of CCl4. The analyses of the results obtained showed significant reduction in the levels of serum biochemical markers for 400 and 600 mg kg-1 bw of CAE protected rats as compared with CCl4 group. In addition, CAE administration reversed liver tissue damaged via increased antioxidants markers. Histopathological examination of CAE treatment on rats showed improved changes to the liver damage caused by CCl4 with no evidence of steatosis and inflammation. This result hence suggests that CAE has marked hepatoprotective and healing activities against CCl4-induced liver damage and could serve as a suitable candidate in drug discovery for the treatment of liver toxicity.
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Mishra, Nidhi, Narayan Prasad Yadav, Vineet Kumar Rai, Priyam Sinha, Kuldeep Singh Yadav, Sanyog Jain e Sumit Arora. "Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance". BioMed Research International 2013 (2013): 1–20. http://dx.doi.org/10.1155/2013/382184.
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Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action.
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Abdu, Suzan, Nouf Juaid, Amr Amin, Mohamed Moulay e Nabil Miled. "Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights". Antioxidants 11, n.º 9 (25 de agosto de 2022): 1645. http://dx.doi.org/10.3390/antiox11091645.
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This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib both in rats chemically induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). Male rats were randomly divided into five groups, namely, control group, HCC induced group, and groups treated with sorafenib, crocin or both crocin and sorafenib. HCC was induced in rats with a single intraperitoneal injection of diethylnitrosamine (DEN), then 2-acetylaminofluorene (2-AAF). The HCC-induced rats showed a significant decrease in body weight compared to animals treated with either or both examined drugs. Serum inflammatory markers (C-reactive protein (CRP); interleukin-6 (IL-6); lactate dehydrogenase (LDH), and oxidative stress markers were significantly increased in the HCC group and were restored upon treatment with either or both of therapeutic molecules. Morphologically, the HCC-induced rats manifested most histopathological features of liver cancer. Treatment with either or both of crocin and sorafenib successfully restored normal liver architecture. The expression of key genes involved in carcinogenesis (TNFα, p53, VEGF and NF-κB) was highly augmented upon HCC induction and was attenuated post-treatment with either or both examined drugs. Treatment with both crocin and sorafenib improved the histopathological and inflammation parameters as compared to single treatments. The in vivo anti-cancer effects of crocin and/or sorafenib were supported by their respective cytotoxicity on HepG2 cells. Crocin and sorafenib displayed an anti-tumor synergetic effect on HepG2 cells. The present findings demonstrated that a treatment regimen with crocin and sorafenib reduced liver toxicity, impeded HCC development, and improved the liver functions.
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Poojari, Radhika, Rohit Srivastava e Dulal Panda. "Microtubule targeted therapeutics loaded polymeric assembled nanospheres for potentiation of antineoplastic activity". Faraday Discussions 186 (2016): 45–59. http://dx.doi.org/10.1039/c5fd00123d.
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Polymeric nanoassemblies represent an attractive strategy for efficient cellular internalization of microtubule targeted anticancer drugs. Using dynamic light scattering, zeta potential, transmission electron microscopy and scanning electron microscopy, the physical properties and surface morphology of microtubule-binding PEGylated PLGA assembled nanospheres (100–200 nm) were analyzed. The present approach leads to strong internalization as observed by confocal laser scanning microscopy and transmission electron microscopy in hepatocarcinoma cells. The effect of these nanoassemblies on microtubules and mitosis were explored using immunofluorescence microscopy. The effects of these nanoassemblies on cancer cell proliferation and cell death revealed their antitumor enhancing effects. Perturbation of the microtubule assembly, mitosis and nuclear modulations potentiated the antineoplastic effects delivered via nanospheres in hepatocarcinoma cells. The extensive biomolecular and physical characterizations of the synthesized nanoassemblies will help to design potent therapeutic materials and the present approach can be applied to deliver microtubule-targeted drugs for liver cancer therapy.
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Weiz, Gisela, Alina L. Gonzalez, Flavia Piccioni, Mariel Fusco, Marco Diaz Gutiérrez, Guillermo Mazzolini, Javier D. Breccia, Mariana Malvicini e Maria I. Molejon. "Abstract 5447: Enhanced antitumoral effect of the glycosylated 4-methylumbelliferone in hepatocellular carcinoma". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 5447. http://dx.doi.org/10.1158/1538-7445.am2022-5447.
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Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, and is particularly refractory to the available therapeutic drugs. Unfortunately, curative treatments such as surgery, liver transplantation, or ablation are reserved for early stages and can only be applied in less than 30% of the patients with HCC. Glycosylation can be a potent and interesting strategy for drug delivery to a specific target. We enzymatically synthesized a glycosylated derivative of the coumarin 4-methylumbelliferone (4MU), namely 4MUR.The antitumoral effect of 4MUR in comparison with the aglycone 4MU was evaluated onto liver cancer cells. Cellular toxicity was determined on murine liver tumor cell lines as well as non-hepatic tumoral cells. Tumor cell lines were significantly more sensitive than non-tumoral cells to the glycosylated molecule in a dose-dependent manner (p<0.05). 4MUR was incorporated mostly into tumoral cells by the interaction with the asialoglycoprotein receptor (ASGPR), which is overexpressed in liver tumor cells. Hyaluronic acid (HA) is the major component of the extracellular matrix (ECM). It is produced at the plasma membrane by three hyaluronan synthases (HAS1, 2 and 3), which couple glucuronic acid and N-acetylglucosamine into a linear polymer using the corresponding UDP-sugars (UDP-GlcUA and UDP-GlcNAc) as substrates. Unlike 4MUR, the glucuronidation of 4MU competitively inhibits chain elongation of HA. Furthermore, 4MUR treatment regulates the levels of HAS2 and HAS3 expression in the tumoral cell line. Finally, 4MUR treatment induced apoptosis cell death in tumoral cells. Our results suggest that the 4MUR is safe and effective against liver tumor cells via a specific targeting to ASGPR receptor and decreasing HA synthesis. Citation Format: Gisela Weiz, Alina L. Gonzalez, Flavia Piccioni, Mariel Fusco, Marco Diaz Gutiérrez, Guillermo Mazzolini, Javier D. Breccia, Mariana Malvicini, Maria I. Molejon. Enhanced antitumoral effect of the glycosylated 4-methylumbelliferone in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5447.
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Pantea, Valeriana, Vitalie Cobzac, Olga Tagadiuc, Victor Palarie e Valentin Gudumac. "In Vitro Evaluation of the Cytotoxic Potential of Thiosemicarbazide Coordinating Compounds in Hepatocyte Cell Culture". Biomedicines 11, n.º 2 (26 de janeiro de 2023): 366. http://dx.doi.org/10.3390/biomedicines11020366.
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Cancer is a global medical problem and, despite research efforts in the field of tumor treatment, there is currently a shortage of specific anticancer drugs. Most anticancer drugs show significant side effects. The liver is the organ that has central functions in drug metabolism, being a major target of the harmful action of anticancer compounds. In this context, it is essential to evaluate the cytotoxic effects of potential anticancer substances. Therefore, hepatotoxicity and hepatocyte viability were determined in vitro to evaluate the action of seven new local thiosemicarbazide coordination compounds (CCT) on normal liver cells. Doxorubicin was used as a reference substance. The control group consisted of hepatocytes not exposed to CCT action. The cell viability of hepatocytes treated with CCT decreased significantly by 5%-12% compared to the control, but was statistically significantly higher by 5%-14% compared to doxorubicin, except after CMD-8 and CMT-67 influence, when it does not change. Thus, new local CCT had a selective effect on hepatocytes in vitro and were less hepatotoxic compared to doxorubicin, which may be the basis for further study of its potential in anticancer drugs.
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Dobrzynska, Malgorzata, Marta Napierala e Ewa Florek. "Flavonoid Nanoparticles: A Promising Approach for Cancer Therapy". Biomolecules 10, n.º 9 (2 de setembro de 2020): 1268. http://dx.doi.org/10.3390/biom10091268.
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Flavonoids, a ubiquitous group of naturally occurring polyphenolic compounds, have recently gained importance as anticancer agents. Unfortunately, due to low solubility, absorption, and rapid metabolism of dietary flavonoids, their anticancer potential is not sufficient. Nanocarriers can improve the bioavailability of flavonoids. In this review we aimed to evaluate studies on the anticancer activity of flavonoid nanoparticles. A review of English language articles published until 30 June 2020 was conducted, using PubMed (including MEDLINE), CINAHL Plus, Cochrane, and Web of Science data. Most studies determining the anticancer properties of flavonoid nanoparticles are preclinical. The potential anticancer activity focuses mainly on MCF-7 breast cancer cells, A549 lung cancer cells, HepG2 liver cancer cells, and melanoma cells. The flavonoid nanoparticles can also support the anti-tumour effect of drugs used in cancer therapy by enhancing the anti-tumour effect or reducing the systemic toxicity of drugs.
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Balabolkin, M. I., e L. B. Nedosugova. "The use of second generation sulfonylurea agents and the role of glurenorm in the therapy of non-insulin-dependent diabetes mellitus". Problems of Endocrinology 41, n.º 2 (15 de abril de 1995): 11–14. http://dx.doi.org/10.14341/probl11362.
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Sulfonylurea drugs stimulate the 1st phase of insulin secretion, activate adenylate cyclase, inhibit phosphodiesterase or cause prolonged depolarization of the beta cell membrane. The peripheral effect of the hypoglycemic action of sulfonylurea drugs is mediated through the effect on insulin receptors. It is clearly shown that sulfonylureas lead to an increase in the number of receptors on target cells (hepatocytes, muscle and adipose tissue, lymphocytes and other cells). It is known that patients with type II diabetes mellitus have a decrease in both the number of receptors and their affinity. The increase in the number of receptors on the membrane of target cells is not due to their de novo synthesis, but by improving the return of the receptor to the membrane from the cytosol, where they are translocated as an insulin-receptor complex after the interaction of insulin with the corresponding receptor.
One of the sulfonylurea drugs of the second generation is Gliquidone (glurenorm). This drug has one advantage, distinguishing it from other sulfonylurea drugs. About 95% of the drug is excreted from the body through the gastrointestinal tract, and only 5% is extracted by the kidneys. Therefore, it is the drug of choice in the treatment of diabetic patients with nephropathy, given the fact that the drug is metabolized in the liver and eliminated through the bile ducts into the intestine. Naturally, the question arises of the possibility of its influence on the liver function of patients who have been receiving long-term treatment with glurenorm.
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Li, Shao-wei, Yue Cai, Xin-li Mao, Sai-qin He, Ya-hong Chen, Ling-ling Yan, Jing-jing Zhou, Ya-qi Song, Li-ping Ye e Xian-bin Zhou. "The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation". Stem Cells International 2021 (4 de setembro de 2021): 1–14. http://dx.doi.org/10.1155/2021/6930263.
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Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.
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Lin, Chun-Ching, Pei-Chen Huang e Jer-Min Lin. "Antioxidant and Hepatoprotective Effects ofAnoectochilus formosanusandGynostemma pentaphyllum". American Journal of Chinese Medicine 28, n.º 01 (janeiro de 2000): 87–96. http://dx.doi.org/10.1142/s0192415x00000118.
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Anoectochilus formosanus Hay. and Gynostemma pentaphyllum Makino are popular folk medicines that have been used for treating hepatitis, hypertension and cancer in Taiwan. Our previous studies showed that these crude drugs exert antiinflammatory activity and hepatoprotective activity against CCI4-induced liver damage. In this study, the antioxidant effect of these crude drugs and their hepatoprotective activity on acetaminophen-induced liver injury in rat was evaluated. Our results suggest that A. formosanus and G. pentaphyllum do have antioxidant effects. On acetaminophen-intoxicated model, the increased levels of aspartate aminotransferase (AST) and alanine aminotrans-ferase (ALT) by acetaminophen administration were reduced by treatment with these two herbs. In histological observation, gross necrosis in the centribular area, sinusoidal congestion, infiltration of the lymphocytes and Kupffer cells around the hepatic central vein, and loss of cell boundaries and ballooning degeneration were reduced with herbal treatment. However, the effect of A. formosanus and G. pentaphyllum is biphasic. Methanol extract (100 and 300 mg/kg) and water extract (300 and 500 mg/kg) of A formosanus and water extract (100, 300 and 500 mg/kg) of G. pentaphyllum enhanced the recovery of liver injury while treatment with 500 mg/kg of A. formosanus methanol extract resulted in serious hepatic injury.
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McVicker, Benita L., Frederick G. Hamel, Ronda L. Simpson e Robert G. Bennett. "A Selective PPARγ Modulator Reduces Hepatic Fibrosis". Biology 9, n.º 7 (2 de julho de 2020): 151. http://dx.doi.org/10.3390/biology9070151.
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Hepatic fibrosis is the accumulation of excess collagen as a result of chronic liver injury. If left unabated, hepatic fibrosis can lead to the disruption of the liver architecture, portal hypertension, and increased risk of progression to cirrhosis and hepatocellular carcinoma. The thiazolidinedione class of antidiabetic drugs, through their target peroxisome proliferator-activated receptor γ (PPARγ), have protective effects against liver fibrosis, and can inhibit the profibrotic activity of hepatic stellate cells, the major collagen-producing liver cells. However, these drugs have been ineffective in the treatment of established fibrosis, possibly due to side effects such as increased weight and adiposity. Recently, selective PPARγ modulators that lack these side effects have been identified, but their role in treating fibrosis has not been studied. In this study, we tested the effectiveness of one of these selective modulators, SR1664, in the mouse carbon tetrachloride model of established hepatic fibrosis. Treatment with SR1664 reduced the total and type 1 collagen content without increasing body weight. The abundance of activated hepatic stellate cells was also significantly decreased. Finally, SR1664 inhibited the profibrotic phenotype of hepatic stellate cells. In summary, a selective PPARγ modulator was effective in the reduction of established hepatic fibrosis and the activated phenotype of hepatic stellate cells. This may represent a new treatment approach for hepatic fibrosis.