Articles de revues sur le sujet « Normal-tissues toxicity »
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Mortezaee, Keywan, Masoud Najafi, Bagher Farhood, Amirhossein Ahmadi, Dheyauldeen Shabeeb et Ahmed E. Musa. « NF‐κB targeting for overcoming tumor resistance and normal tissues toxicity ». Journal of Cellular Physiology 234, no 10 (25 mars 2019) : 17187–204. http://dx.doi.org/10.1002/jcp.28504.
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Mortezaee, Keywan, Masoud Najafi, Bagher Farhood, Amirhossein Ahmadi, Dheyauldeen Shabeeb et Ahmed E. Musa. « Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization ». Current Cancer Drug Targets 20, no 2 (11 février 2020) : 130–45. http://dx.doi.org/10.2174/1568009619666191019143539.
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Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.
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Najafi, Masoud, Elahe Motevaseli, Alireza Shirazi, Ghazale Geraily, Abolhasan Rezaeyan, Farzad Norouzi, Saeed Rezapoor et Hamid Abdollahi. « Mechanisms of inflammatory responses to radiation and normal tissues toxicity : clinical implications ». International Journal of Radiation Biology 94, no 4 (7 mars 2018) : 335–56. http://dx.doi.org/10.1080/09553002.2018.1440092.
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Picut, Catherine A., et George A. Parker. « Postnatal Organ Development as a Complicating Factor in Juvenile Toxicity Studies in Rats ». Toxicologic Pathology 45, no 1 (17 octobre 2016) : 248–52. http://dx.doi.org/10.1177/0192623316671609.
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Toxicologic pathologists must evaluate tissues of immature animals from a number of types of nonclinical toxicity studies. The pathologist who is familiar with normal postnatal organ development is in a better position to appropriately detect and differentiate between abnormal, delayed, or precocious development. Vacuolation and apoptosis in multiple tissue types are normal components of development that could influence the interpretation of some tissues. Unique postnatal features such as the germal matrix in the brain, gonocytes in the testes, and saccules in the lung may complicate the histopathological evaluation. With the knowledge of normal organ development and critical windows therein, it is possible to design targeted studies to identify xenobiotic toxicity.
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Lee, F. Y., et P. Workman. « Misonidazole protects mouse tumour and normal tissues from the toxicity of oral CCNU ». British Journal of Cancer 51, no 1 (janvier 1985) : 85–91. http://dx.doi.org/10.1038/bjc.1985.12.
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Linard, Christine, et Maâmar Souidi. « PPARs in Irradiation-Induced Gastrointestinal Toxicity ». PPAR Research 2010 (2010) : 1–12. http://dx.doi.org/10.1155/2010/528327.
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The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in irradiation toxicity, and the possibility of using their ligands for radioprotection.
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&NA;. « Amifostine protects a broad range of normal tissues from chemotherapy- and radiotherapy-associated toxicity ». Drugs & ; Therapy Perspectives 17, no 21 (octobre 2001) : 1–5. http://dx.doi.org/10.2165/00042310-200117210-00001.
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Taylor, C. W., L. M. Wang, A. F. List, D. Fernandes, G. D. Paine-Murrieta, C. S. Johnson et R. L. Capizzi. « Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained ». European Journal of Cancer 33, no 10 (septembre 1997) : 1693–98. http://dx.doi.org/10.1016/s0959-8049(97)00221-9.
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Chen, Nan, Yuping Han, Yao Luo, Yanfeng Zhou, Xingjie Hu, Yun Yu, Xiaodong Xie et al. « Nanodiamond-based non-canonical autophagy inhibitor synergistically induces cell death in oxygen-deprived tumors ». Materials Horizons 5, no 6 (2018) : 1204–10. http://dx.doi.org/10.1039/c8mh00993g.
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Ke, Yong, Keqiang Ye, Hans E. Grossniklaus, David R. Archer, Harish C. Joshi et Judith A. Kapp. « Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses ». Cancer Immunology, Immunotherapy 49, no 4-5 (19 juin 2000) : 217–25. http://dx.doi.org/10.1007/s002620000109.
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Siregar, Fazwishni, et Rini Damayanti. « Acute Toxicity of Jatropha Curcas L. Latex and Its Histopathological Effects on Dental Pulp and Periapical Tissues ». Majalah Obat Tradisional 25, no 1 (30 avril 2020) : 15. http://dx.doi.org/10.22146/mot.46303.
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Traditional uses of Jatropha curcas L. latex,among others, are to cure toothache. This study aimed to evaluate the acute toxicity of J. curcas latex by oral route and to assess the histopathological effects of J. curcas latex on dental pulp and periapical tissues. For acute toxicity, the latex of 5 g/kg BW was administered intragastrically to the test groups of albino mice and water to the control groups. The assessment was based upon mortality, sign of toxicity, body weight, and histological evaluation of organs. Results showed no mortality in mice up to 5 g/kg body weight, no sign of toxicity, and no tissue alterations macroscopically and histopathologically were observed. There’s no significant difference in body weight between the test and control, both in male and female groups. For testing histopathologic effect on dental pulp, the latex was brought in contact with dental pulp and sealed. The assessment was based on the presence of inflammation and necrosis in dental pulp and periapical tissues, histopathologically. Results showed inflammation and necrosis, which was in direct contact with the latex were observed in a limited area, while underneath was normal pulp. No inflammation or necrosis in periapical tissues was observed in all groups. It caused coagulative necrosis in the pulp which was in direct contact with latex. It can be concluded that J. curcas latex is slightly toxic to mice at a single dose of oral administration. Inflammation and necrosis are observed on dental pulp which is in contact with latex while the tissue underneath is normal. It did not caused inflammation on periapical tissues.
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Hou, Jia, Xiaoyan Sun, Ying Huang, Shaohua Yang, Junjie Liu, Changhao Feng, Jun Ma et Bin Chen. « The Design and Application of Nanomaterials as Drug Carriers in Cancer Treatment ». Current Medicinal Chemistry 27, no 36 (4 novembre 2020) : 6112–35. http://dx.doi.org/10.2174/0929867326666190816231409.
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The development of new medical cancer treatment technologies is of great significance in reducing cancer mortality. Traditional clinical cancer therapy has a short drug action time, difficulty in accurately targeting tumour tissues and high levels of toxicity in normal tissues. With the development of nanotechnology, nanomaterials have been used as drug carriers to specifically target cancer cells and release drugs into the tumour environment. This technique has become an important research hotspot in cancer treatment. There are several advantages of using nanomaterials for cancer treatment that improve the efficacy of drug delivery, including increased drug concentrations in the targeted tumour area, reduced toxicity in normal tissues and controlled drug release. In this work, we describe the latest research development on the use of nanomaterials for drug delivery in cancer treatment and explore related mechanistic pathways. In addition, the methods used to control drug release into the targeted area using nanocarriers are reviewed in detail. Overall, we present current achievements using nanomaterials and nanotechnologies in cancer treatment, followed by current challenges and future prospects.
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Nusair, SD, AN Joukhan, AH Bani Rashaid et AM Rababa’h. « Methomyl induced effect on fortilin and S100A1 in serum and cardiac tissue : Potential biomarkers of toxicity ». Human & ; Experimental Toxicology 38, no 3 (25 novembre 2018) : 371–77. http://dx.doi.org/10.1177/0960327118814153.
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Methomyl toxicity has been reported as a cause of several accidental and suicidal fatalities. The study is evaluating the effect of lethal methomyl toxicity on fortilin and S100A1 in serum and cardiac tissues. Adult 96 female Sprague-Dawley rats were divided equally into a control (euthanized by cervical dislocation) and a study group (overdosed with methomyl). The levels of fortilin and S100A1 in serum were measured antemortem (to establish the basal levels in serum) and postmortem (to evaluate changes after methomyl exposure) using enzyme-linked immunoassay. S100A1 was immunostained in sections from cardiac tissues. Both proteins in the control were not significantly different ( p > 0.05) compared with the antemortem levels. On the contrast, both biomarkers levels in the intoxicated group were remarkably higher ( p < 0.001) than the control and the antemortem levels. Ventricular tissues from the intoxicated rats presented depleted S100A1 immunostain in cardiomyocytes localized mainly in the epicardium with deeply stained adjacent cardiac fibroblasts. The cardiomyocytes were damaged with a prominent loss of striations compared to normal cardiac tissues from the control. The present outcomes explain to a certain degree the potential toxic effect of methomyl poisoning on the cardiac tissue. Both proteins could be added to the currently available battery of markers for assessing methomyl toxicity.
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Tahmasebi, Kavoos, Mahvash Jafari, Javad Heydari, Alireza Asgari, Maryam Salehi, Saeed Khazaie et Mohammad Saleh Abedini. « Tissues toxicity attenuation by vitamin E on oxidative damage induced by diazinon ». Environmental Analysis Health and Toxicology 37, no 4 (10 novembre 2022) : e2022036. http://dx.doi.org/10.5620/eaht.2022036.
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Organophosphorus insecticides such as diazinon (DZN) are used worldwide in industry, veterinary practice, and agriculture. They may induce oxidative stress in different tissues. The use of antioxidants can protect tissues against oxidative stress. The aim of this study was to investigate the prophylactic and therapeutic roles of vitamin E against DZN–induced oxidative damage and biochemical alterations in various tissues of male Wistar rats. Thirty rats were divided into five groups: Control group received only corn oil as DZN solvent, DZN group received 100 mg/kg of DZN, E group received 150 mg/kg of vitamin E, E-DZN group received vitamin E and then dosed with DZN and DZN-E group received DZN and then dosed with vitamin E. All injections were carried out intraperitoneally. Plasma and various tissues were prepared and evaluated. Results showed that acute administration of DZN caused a significant induction of oxidative damage in the tested tissues via increased malondialdehyde level and some plasma biochemical indices, depletion of glutathione (GSH), reduced cholinesterase activity and change in the activities of superoxide dismutase, catalase and glutathione-S transferase. Treatment of rats with vitamin E resulted in an elevation in the level of GSH, normalizing the antioxidant enzymes activities and decreasing lipid peroxidation, although all these tests did not return to the normal level in certain tissues. The findings of this study suggest that both prophylactic and therapeutic treatments of rats with vitamin E provide a protective role against DZN-induced oxidative stress and cholinergic hyperactivity through free radicals scavenging and membrane stabilizing.
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Pardo, Ingrid D., Klaus Weber, Sarah Cramer, Georg J. Krinke, Mark T. Butt, Alok K. Sharma et Brad Bolon. « Atlas of Normal Microanatomy, Procedural and Processing Artifacts, Common Background Findings, and Neurotoxic Lesions in the Peripheral Nervous System of Laboratory Animals ». Toxicologic Pathology 48, no 1 (19 août 2019) : 105–31. http://dx.doi.org/10.1177/0192623319867322.
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The ability to differentiate among normal structures, procedural and processing artifacts, spontaneous background changes, and test article–related effects in the peripheral nervous system (PNS) is essential for interpreting microscopic features of ganglia and nerves evaluated in animal species commonly used in toxicity studies evaluating regulated products and chemicals. This atlas provides images of findings that may be encountered in ganglia and nerves of animal species commonly used in product discovery and development. Most atlas images are of tissues from control animals that were processed using routine methods (ie, immersion fixation in neutral-buffered 10% formalin, embedding in paraffin, sectioning at 5 µm, and staining with hematoxylin and eosin) since these preparations are traditionally applied to study materials produced during most animal toxicity studies. A few images are of tissues processed using special procedures (ie, immersion or perfusion fixation using methanol-free 4% formaldehyde, postfixation in glutaraldehyde and osmium, embedding in hard plastic resin, sectioning at 1 µm, and staining with toluidine blue), since these preparations promote better stabilization of lipids and thus optimal resolution of myelin sheaths. Together, this compilation provides a useful resource for discriminating among normal structures, procedure- and processing-related artifacts, incidental background changes, and treatment-induced findings that may be seen in PNS tissues of laboratory animals.
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Ghilotti, Marco, Marco Alessandro Pierotti et Manuela Gariboldi. « Molecular markers for prediction of risk of radiation-related injury to normal tissue ». Journal of Nucleic Acids Investigation 1, no 1 (11 octobre 2010) : 11. http://dx.doi.org/10.4081/jnai.2010.2055.
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Radiotherapy is one of the most effective methods for the treatment of cancer, but occurrence of adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Identification of individuals at risk of severe reaction is very difficult and considerable efforts have been made to correlate normal tissue toxicity with cellular responses to ionizing radiation. Genetic markers enabling to identify hyper-sensitive patients prior to treatment would considerably improve its outcome. Gene association studies should help to identify such markers. Expression levels of specific transcripts could be putative markers; in fact different studies found associations between gene expression profiles in normal cells and the reaction of normal tissues to radiation therapy. The finding that ionizing radiation induces the deregulation of a high number of genes suggests that also microRNAs that affect the expression of a large number of target genes may be involved. This review briefly introduces the mechanisms of radiation-induced normal tissue toxicity and summarizes clinical research focused on the evaluation of molecular biomarkers for predicting risk of injury to normal tissue, mainly describing gene transcripts alterations.
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Maksimov, Maksim Leonidovich, et Malika Anarbekovna Ismailova. « Adverse reactions during chemotherapy : skin toxicity ». Vrač skoroj pomoŝi (Emergency Doctor), no 9 (1 septembre 2020) : 28–64. http://dx.doi.org/10.33920/med-02-2009-01.
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Chemotherapy of oncological diseases is associated with high toxicity. The occurrence of various toxic reactions during the use of antitumor drugs is explained by the fact that most antitumor medicines are not strictly specific, therefore, their effect can extend not only to tumor cells, but also to normal cells, especially to tissues with rapid proliferation. All antitumour agents have skin toxicity in one form or another. However, for some chemotherapeutic agents, skin toxicity is a kind of «reflection» of certain mechanisms of drugs action, and, in most cases, the severity of dermatological reactions correlates with the effectiveness of chemotherapy. Dermatological toxicity deserves special attention, as it affects the quality of life of cancer patients and, in some cases, may require a dose reduction or even cancellation of chemotherapy. This article presents current data on the mechanisms of development of skin toxicity of routine chemotherapeutic agents, growth factor inhibitors and some antitumor antibiotics, its correction and prevention opportunities.
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Mulyani, Yani, Patonah Hasimun et Siti Nurjanah. « Subcrhonic Toxicity of Curcuma longa (Tumeric) Rhizoma Extract on Rats ». Majalah Obat Tradisional 27, no 2 (31 août 2022) : 111. http://dx.doi.org/10.22146/mot.72259.
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Toxicity is a condition that indicates a harmful effect contained in a substance such as turmeric, which is an effective traditional medicinal plant used for antihypertensive treatment. Therefore, this study aims to determine the effect of repeated dosing of turmeric (Curcuma longa L.) rhizome extract. This subchronic toxicity study was divided into 4 groups, namely 1 normal treated with 0.5% Na-CMC, and 3 treatments with turmeric extract at doses of 50, 100, and 200 mg/kg BW for 28 days with each group consisting of 5 males and 5 female Wistar rats. The results showed that the turmeric extract at doses of 50, 100, and 200 mg/kg BW did not cause toxicity to liver and kidney biochemistry nor contain any toxic substances that might cause anemia or other abnormalities. Furthermore, histopathological examination showed that the tissues were normal. This indicates that the turmeric rhizome extract at all dose variations indicate non-toxic when used in traditional medicine.
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Sistani Karampour, Neda, Mohammad Javad Bagheri, Laya Sadat Khorsandi, Zeinab Dehghan Mohammadi et Maryam Salehcheh. « Investigating the Safety of Bee Pollen on Performance, Oxidative Stress, and Histopathological Changes in the Liver, Kidney, and Pancreas of Rats ». Complementary Medicine Journal 11, no 4 (1 janvier 2022) : 330–45. http://dx.doi.org/10.32598/cmja.11.4.1094.1.
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Objective: The therapeutic effects of bee pollen have already been proven in various studies, but toxicity studies in this field are limited. Therefore, in this study, the possible toxicity effects of hydroalcoholic extract of flower pollen on liver, kidney, and pancreatic tissues of male rats are investigated. Methods: Fourteen male rats were divided into two groups of seven: the first group received 800 mg/kg hydroalcoholic extract of bee pollen, and the second group received 0.5 mL/100 g normal saline intraperitoneally for 1 day. Then, their livers, kidney, pancreas, and oxidative stress biomarkers were evaluated. In addition, pieces of liver, kidney, and pancreatic tissues were examined histopathologically. Results: Blood urea nitrogen (BUN) (P =0.0212), aspartate aminotransferase (AST) enzymes (P =0.0344), and malondialdehyde (MDA) biomarker (P =0.018) of kidney tissue were significantly decreased in the hydroalcoholic extract of bee pollen group compared to the control group. The glutathione (GSH) biomarker of kidney tissue showed a significant increase in this group compared to the control group (P =0.0031). The other evaluated parameters were not significantly different between the two groups (P> 0.05). Histopathologically, no deleterious and toxicity effects were observed in the tissues. Conclusion: Bee pollen has therapeutic properties and, as a nutrient, can be useful and effective for humans. In this study, this substance did not have toxicity effects on the liver, kidney, and pancreas and even protected vital organs in oxidative stress conditions. However, more research is needed to prove the toxicity of this valuable substance and to ensure its safety.
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Lapin, C., Q. Bui, R. Breglia, F. Koschier, P. Podhasky, E. Lapadula, R. Roth et al. « Toxicity Evaluation of Petroleum Blending Streams : Inhalation Subchronic Toxicity/Neurotoxicity Study of a Light Catalytic Cracked Naphtha Distillate in Rats ». International Journal of Toxicology 20, no 5 (septembre 2001) : 307–19. http://dx.doi.org/10.1080/109158101753253045.
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A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741–55–5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2μ-globulin accumulation was seen in mid-and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was ≥7500 ppm.
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Floyd, Justin D., Duc T. Nguyen, Raymond L. Lobins, Qaiser Bashir, Donald C. Doll et Michael C. Perry. « Cardiotoxicity of Cancer Therapy ». Journal of Clinical Oncology 23, no 30 (20 octobre 2005) : 7685–96. http://dx.doi.org/10.1200/jco.2005.08.789.
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Because cancer is a leading cause of mortality in the United States, the number of therapeutic modalities available for the treatment of neoplastic processes has increased. This has resulted in a large number of patients being exposed to a wide variety of cancer therapy. Historically, it has been well recognized that antineoplastic agents may have adverse effects on multiple organs and normal tissues. The most commonly associated toxicities occur in tissues composed of rapidly dividing cells and may spontaneously reverse with minimal long-term toxicity. However, the myocardium consists of cells that have limited regenerative capability, which may render the heart susceptible to permanent or transient adverse effects from chemotherapeutic agents. Such toxicity encompasses a heterogeneous group of disorders, ranging from relatively benign arrhythmias to potentially lethal conditions such as myocardial ischemia/infarction and cardiomyopathy. In some instances, the pathogenesis of these toxic effects has been elucidated, whereas in others the precise etiology remains unknown. We review herein the various syndromes of cardiac toxicity that are reported to be associated with antineoplastic agents and discuss their putative mechanisms and treatment.
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Cho, L. Chinsoo, Robert Timmerman et Brian Kavanagh. « Hypofractionated External-Beam Radiotherapy for Prostate Cancer ». Prostate Cancer 2013 (2013) : 1–11. http://dx.doi.org/10.1155/2013/103547.
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There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity.
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Parekh, Palak R., Christophe E. Redon, Urbain Weyemi et William Bonner. « Examining the reliability of surrogate tissue predictability of drug efficacy in reconstituted human 3D skin models containing melanomas. » Journal of Clinical Oncology 30, no 30_suppl (20 octobre 2012) : 49. http://dx.doi.org/10.1200/jco.2012.30.30_suppl.49.
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49 Background: Melanoma has a poor survival rate in advanced stages due to the lack of efficacious approved treatments. However, melanoma’s dermal location enables the application of human skin models. These models mimic many important characteristics of skin in vivo and obviate the use of invasive procedures. Monitoring gamma-H2AX foci to assess DNA double-strand break (DSB) levels in reconstituted human 3D skin tissue harboring melanoma tumor cells may provide insights into important questions in cancer research. In addition to the differential toxicities of anti-cancer agents on the various cell types, we examine how the early drug response of normal tissues might serve as surrogates for predicting treatment efficacy on the tumors. Methods: Commercially available reconstituted 3D human skin tissue consists of dermal fibroblast and epidermal keratinocyte layers with malignant melanoma A375 cells which have been cultured to form a multilayer, highly differentiated epidermis containing various stages of cutaneous melanoma malignancy. Drugs representative of several different categories were studied, including bleomycin (a radiomimetic), camptothecin (a topoisomerase I inhibitor), temozolomide (a DNA alkylating agent), AZD6244 (a MEK inhibitor), Vorinostat (a HDAC inhibitor) and cisplatin (a DNA intercalatingagent). DNA DSB levels were monitored by gamma-H2AX foci formation and apoptosis by TUNEL assay. Tumor growth was monitored by H&E staining. Results: A wide range of responses in both tumor and normal tissue by various drugs were observed, including tumor regression and normal tissue toxicity. The early responses of normal tissues depended on the treatment, providing insights into the use of surrogate tissues as predictors of drug efficacy and later tumor regression. Conclusions: Measuring DNA DSB damage in reconstituted 3D skin tissue is an attractive model for studying the efficacy and toxicity of genotoxic drugs against melanoma. If validated, such models would help reduce the use of animals for preclinical studies.
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Volkan Gelen et Emin Şengül. « Protective effects of resveratrol on kidney function tests and renal histopathology in carbon tetrachloride-induced renal toxicity in rats ». World Journal of Advanced Research and Reviews 10, no 1 (30 avril 2021) : 156–61. http://dx.doi.org/10.30574/wjarr.2021.10.1.0155.
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In this study, it was aimed to investigate the protective effect of Resveratrol, which has a strong antioxidant effect on kidney tissues of rats experimentally induced with carbon tetrachloride with nephrotoxicity, by kidney function tests and histopathology. For this purpose, 32 male Wistar Albino rats were used. The subjects were randomly selected, 1st group control, 2nd group CCl4, 3rd group Resveratrol. The 4th group was divided into 4 groups as CCl4 + Resveratrol. At the end of the experiment, animals were sacrificed under anesthesia and kidney samples were taken in 10% formalin solution for histopathological analysis. In the histopathological examination, it was found that the rats in the control and Resveratrol groups had normal kidney histological structure. In CCI4 group, severe hydropic degeneration in tubules epithelium, mild coagulation necrosis in tubules epithelium and severe hyperemia in the vessels were observed. When kidney tissues of rats were examined in CCI4 + Resveratrol group, mild hydropic degeneration in tubules epithelium and mild hyperemia in vessels were observed. When the kidney tissues of the rats in the Resveratrol group were examined, it was observed that they had a normal histological appearance. As a result, it was determined that Resveratrol has a protective effect on kidney damage caused by CCI4.
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Alonso-Camino, Vanesa, Seandean Lykke Harwood, Ana Álvarez-Méndez et Luis Alvarez-Vallina. « Efficacy and toxicity management of CAR-T-cell immunotherapy : a matter of responsiveness control or tumour-specificity ? » Biochemical Society Transactions 44, no 2 (11 avril 2016) : 406–11. http://dx.doi.org/10.1042/bst20150286.
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Chimaeric antigen receptor (CAR)-expressing T-cells have demonstrated potent clinical efficacy in patients with haematological malignancies. However, the use of CAR-T-cells targeting solid tumour-associated antigens (TAAs) has been limited by organ toxicities related to activation of T-cell effector functions through the CAR. Most existing CARs recognize TAAs, which are also found in normal tissues. CAR-T-cell-mediated destruction of normal tissues constitutes a major roadblock to CAR-T-cell therapy, and must be avoided or mitigated. There is a broad range of strategies for modulating antigen responsiveness of CAR-T-cells, with varying degrees of complexity. Some of them might ameliorate the acute and chronic toxicities associated with current CAR constructs. However, further embellishments to CAR therapy may complicate clinical implementation and possibly create new immunogenicity issues. In contrast, the development of CARs targeting truly tumour-specific antigens might circumvent on-target/off-tumour toxicities without adding additional complexity to CAR-T-cell therapies, but these antigens have been elusive and may require novel selection strategies for their discovery.
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May, C., R. Gunther et RS McIvor. « Protection of mice from lethal doses of methotrexate by transplantation with transgenic marrow expressing drug-resistant dihydrofolate reductase activity ». Blood 86, no 6 (15 septembre 1995) : 2439–48. http://dx.doi.org/10.1182/blood.v86.6.2439.bloodjournal8662439.
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Marrow cells from previously established lines of transgenic mice expressing either of two different methotrexate (MTX)-resistant dihydrofolate reductases (DHFRs) were transplanted into recipient animals to determine the resultant in vivo protective effect against toxicity associated with MTX administration. Sublethally irradiated, untransplanted animals were first used to establish conditions of low- dose MTX administration resulting in substantial hematopoietic toxicity with undetectable gastrointestinal toxicity. Under these conditions, low survival rates were observed for normal or transgenic animals not expressing drug-resistant DHFR activity, whereas transgenic animals expressing either the arg22 (line 04) or trp31 (line 03) DHFR variants survived. Transplantation of 10(6) marrow cells from either transgenic lines 03 or 04 rescued normal FVB/N recipient animals from low-dose MTX administration, which was lethal for animals transplanted with 10(6) normal FVB/N marrow cells. Reduced survival of transgenic line 04 marrow recipients was observed when twofold or fourfold doses of MTX were administered. However, when 10(7) transgenic line 04 marrow cells were infused, the recipients were found to be resistant to a MTX dose that was not only lethal for animals transplanted with 10(7) normal FVB/N marrow cells, but also lethal for normal, untransplanted FVB/N mice. Histologic analysis showed protection of both marrow and gastrointestinal tissues from MTX toxicity in transgenic line 04 marrow transplant recipients. Thus, exclusive expression of MTX-resistant DHFR activity in the marrow had a substantial, systemic chemoprotective effect in animals, which could be applied for improved utilization of MTX for antitumor chemotherapy.
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Rahman, Heshu Sulaiman, Abdullah Rasedee, Hemn Hassan Othman, Max Stanley Chartrand, Farideh Namvar, Swee Keong Yeap, Nozlena Abdul Samad et al. « Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model ». BioMed Research International 2014 (2014) : 1–15. http://dx.doi.org/10.1155/2014/563930.
Texte intégralRésumé :
Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effectin vitrowas evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.
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Ramot, Yuval, Shlomo Nedvetzki, Sefi Rosenfeld, Noam Emanuel et Abraham Nyska. « Toxicity and Safety Study of D-PLEX100 in a Sternal Surgical Defect in New Zealand White Rabbits ». Toxicologic Pathology 47, no 4 (11 avril 2019) : 504–14. http://dx.doi.org/10.1177/0192623319837887.
Texte intégralRésumé :
Bacterial infections are a common complication after surgical procedures. Therefore, local delivery of antibiotics has been developed, including the use of biodegradable polymers. A newly developed product for prevention of surgical site infections is a polymer–lipid encapsulation matrix loaded with doxycycline, named D-PLEX100 (D-PLEX). We evaluated the toxicity and safety of D-PLEX using a sternal surgical defect model in rabbits. D-PLEX was tested with three different concentrations of doxycycline in comparison to sham-operated control after administration into the sternal surgical defect and on the ventral side of the sternum in New Zealand White (NZW) rabbits, following 15 months of exposure. No mortality or abnormal clinical findings were attributed to D-PLEX, and clinical pathology assays were normal. Histological examinations revealed no treatment-related adverse findings in any of the examined tissues, including the osseous and surrounding soft tissues. It has been shown that D-PLEX gradually degraded until complete disappearance after 9 months, and mainly during the first 3 months, in parallel to normal bone formation. In addition, the administration of D-PLEX did not affect sternal bone strength. This study adds to the growing data on preclinical safety studies utilizing biodegradable materials and provides information on the expected normal reaction to biodegradable materials in the sternum of NZW rabbits.
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Alkhedaide, Adel Qlayel. « Anti-inflammatory Effect of Juniperus Procera Extract in Rats Exposed to Streptozotocin Toxicity ». Anti-Inflammatory & ; Anti-Allergy Agents in Medicinal Chemistry 18, no 1 (6 février 2019) : 71–79. http://dx.doi.org/10.2174/1871523018666181126124336.
Texte intégralRésumé :
Background: Chronic inflammation is a critical health issue and implicated in several chronic health problems such as tumors, auto-immune disorder, hypertension or diabetes. However, Juniperus procera is one of the famous ancient plants that has been traditionally used to treat several diseases such as hyperglycemia, hepatitis, jaundice, bronchitis, and pneumonia. </P><P> Objective: Current study is an attempt to investigate the anti-inflammatory effect of Juniperus procera extract on rats exposed to cytotoxicity caused experimentally by streptozotocin injections. </P><P> Methods: Five groups of adult Wistar rats (10 rats each) were examined as (Normal control, Normal rats treated with Juniperus procera extract, rats administrated with streptozotocin, rats administrated with streptozotocin and treated with insulin and, rats administrated with streptozotocin and Juniperus procera extract). At the end of the experiment, blood was collected from experimented rats. Animals then were killed and small parts of both pancreas and liver were collected for gene expression and histopathological examination. </P><P> Results: Serum analysis showed a significant increase in glucose, IL-6, IL-2 and TNF-α levels in rats exposed to streptozotocin. That change was reduced in rats cotreated with insulin or Juniperus procera extract. Moreover, streptozotocin showed a significant upregulation of IL-6, TNF-α and A2M genes, while, either insulin or Juniperus procera treatment was restored to normal status. Streptozotocin induced inflammation within hepatic tissues which clearly reduced in hepatic tissues of both insulin and junipers cotreated groups. </P><P> Conclusion: Streptozotocin toxicity induces acute inflammation and increases serum glucose, IL-6, IL-2 and TNF-α levels. However, Juniperus procera extract was found to significantly prevent that reaction within four weeks experimented frame time.
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Shakil, Md Salman, Md Ashraful Hasan et Satya Ranjan Sarker. « Iron Oxide Nanoparticles for Breast Cancer Theranostics ». Current Drug Metabolism 20, no 6 (17 juillet 2019) : 446–56. http://dx.doi.org/10.2174/1389200220666181122105043.
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Background: Breast cancer is the second leading cause of death in women worldwide. The extremely fast rate of metastasis and ability to develop resistance mechanism to all the conventional drugs make them very difficult to treat which are the causes of high morbidity and mortality of breast cancer patients. Scientists throughout the world have been focusing on the early detection of breast tumor so that treatment can be started at the very early stage. Moreover, conventional treatment processes such as chemotherapy, radiotherapy, and local surgery suffer from various limitations including toxicity, genetic mutation of normal cells, and spreading of cancer cells to healthy tissues. Therefore, new treatment regimens with minimum toxicity to normal cells need to be urgently developed. Methods: Iron oxide nanoparticles have been widely used for targeting hyperthermia and imaging of breast cancer cells. They can be conjugated with drugs, proteins, enzymes, antibodies or nucleotides to deliver them to target organs, tissues or tumors using external magnetic field. Results: Iron oxide nanoparticles have been successfully used as theranostic agents for breast cancer both in vitro and in vivo. Furthermore, their functionalization with drugs or functional biomolecules enhance their drug delivery efficiency and reduces the systemic toxicity of drugs. Conclusion: This review mainly focuses on the versatile applications of superparamagnetic iron oxide nanoparticles on the diagnosis, treatment, and detecting progress of breast cancer treatment. Their wide application is because of their excellent superparamagnetic, biocompatible and biodegradable properties.
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Aamir, Khurram, Hidayat Ullah Khan, Chowdhury Faiz Hossain, Mst Rejina Afrin, Imam Shaik, Naguib Salleh, Nelli Giribabu et Aditya Arya. « Oral toxicity of arjunolic acid on hematological, biochemical and histopathological investigations in female Sprague Dawley rats ». PeerJ 7 (22 novembre 2019) : e8045. http://dx.doi.org/10.7717/peerj.8045.
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Background Arjunolic acid (AA) is a potent phytochemical with wider pharmacological activities. Despite potential medicinal properties on various in vitro and in vivo studies, there is still a dearth of scientific data related to its safety profile and toxicological parameters. The current study aimed to investigate acute toxicity of AA in normal female Sprague Dawley rats. Methods In this study, AA was administered orally at an individual dose of 300 and 2000 mg/kg body weight to group 1 and 2 respectively, while group 3 served as normal control. All the animals were observed for 2 weeks to determine any behavioral and physical changes. On day 15, blood was collected for hematological and biochemical investigation, later animals from all the three groups were euthanized to harvest and store essential organs for histopathological analysis. Four different staining techniques; hematoxylin and eosin, Masson trichrome, Periodic acid Schiff and Oil O Red were used to investigate any alterations in different tissues through microscopical observation. Results The results of the study showed no morbidity and mortality at two different dosage of AA treatment. Daily food & water intake, body weight, relative organ weight, hematological and biochemical parameters were detected to be normal with no severe alteration seen through microscopical investigation in the structure of harvested tissues. Our findings support the safety profile of AA, which was well tolerated at higher dose. Thus, an in-detail study on the subacute disease model is warranted.
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Schlaak, Rachel A., Gopika SenthilKumar, Marjan Boerma et Carmen Bergom. « Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity ». Cancers 12, no 2 (11 février 2020) : 415. http://dx.doi.org/10.3390/cancers12020415.
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Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.
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Tasian, Sarah K. « Acute myeloid leukemia chimeric antigen receptor T-cell immunotherapy : how far up the road have we traveled ? » Therapeutic Advances in Hematology 9, no 6 (17 mai 2018) : 135–48. http://dx.doi.org/10.1177/2040620718774268.
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Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority. Tumor antigen-redirected chimeric antigen receptor (CAR) T-cell immunotherapies have induced remarkable responses in patients with relapsed or chemorefractory B-lymphoblastic leukemia, and similar strategies are now under early clinical study in adults with relapsed/refractory AML. However, potential on target/off tumor toxicity of AML CAR T-cell immunotherapies, notably aplasia of normal myeloid cells, may limit broader implementation of such approaches. Careful selection of optimal target antigens, consideration of toxicity mitigation strategies, and development of methodologies to circumvent potential CAR T-cell resistance are essential for successful implementation of cellular immunotherapies for patients with high-risk AML.
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Alhussan, Abdulaziz, Nolan Jackson, Sarah Eaton, Nancy Dos Santos, Ingrid Barta, Josh Zaifman, Sam Chen, Yuen Yi C. Tam, Sunil Krishnan et Devika B. Chithrani. « Lipid-Nanoparticle-Mediated Delivery of Docetaxel Prodrug for Exploiting Full Potential of Gold Nanoparticles in the Treatment of Pancreatic Cancer ». Cancers 14, no 24 (13 décembre 2022) : 6137. http://dx.doi.org/10.3390/cancers14246137.
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Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNPDTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNPDTX-P. For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously in NRG mice, and the mice were dosed with 2 mg/kg of GNPs and 6 mg/kg of DTX or an equivalent dose of LNPDTX-P. The results show that LNPDTX-P-treated tumour samples had double the amount GNPs compared to control samples, both in vitro and in vivo. The results are very promising, as LNPDTX-P have superior targeting of tumour tissues compared to free DTX due to their nanosize and their ability to be functionalized. Because of their minimal toxicity to normal tissues, both GNPs and LNPDTX-P could be ideal radiosensitization candidates in radiotherapy and would produce very promising synergistic therapeutic outcomes.
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Xiong, Menghua, Yan Bao, Xin Xu, Hua Wang, Zhiyuan Han, Zhiyu Wang, Yeqing Liu et al. « Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides ». Proceedings of the National Academy of Sciences 114, no 48 (13 novembre 2017) : 12675–80. http://dx.doi.org/10.1073/pnas.1710408114.
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Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix–coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)m-r-(PHLG-MHH)n, bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6-N-(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori, including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues.
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Larrey, Enoch K., et Rupak Pathak. « Radiation-Induced Intestinal Normal Tissue Toxicity : Implications for Altered Proteome Profile ». Genes 13, no 11 (2 novembre 2022) : 2006. http://dx.doi.org/10.3390/genes13112006.
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Radiation-induced toxicity to healthy/normal intestinal tissues, especially during radiotherapy, limits the radiation dose necessary to effectively eradicate tumors of the abdomen and pelvis. Although the pathogenesis of intestinal radiation toxicity is highly complex, understanding post-irradiation alterations in protein profiles can provide crucial insights that make radiotherapy safer and more efficient and allow for increasing the radiation dose during cancer treatment. Recent preclinical and clinical studies have advanced our current understanding of the molecular changes associated with radiation-induced intestinal damage by assessing changes in protein expression with mass spectrometry-based approaches and 2-dimensional difference gel electrophoresis. Studies by various groups have demonstrated that proteins that are involved in the inflammatory response, the apoptotic pathway, reactive oxygen species scavenging, and cell proliferation can be targeted to develop effective radiation countermeasures. Moreover, altered protein profiles serve as a crucial biomarkers for intestinal radiation damage. In this review, we present alterations in protein signatures following intestinal radiation damage as detected by proteomics approaches in preclinical and clinical models with the aim of providing a better understanding of how to accomplish intestinal protection against radiation damage.
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Kauser, S. H., S. Tasneem et R. Yasmeen. « HISTOPATHOLOGICAL STUDIES OF SELECTED ORGANS OF OREOCHROMIS MOSSAMBICUS EXPOSED TO BIOPESTICIDE ACHOOK – SHORT TERM AND LONG TERM TOXICITY ». Journal of Biopesticides 9, no 2 (1 décembre 2016) : 189–95. http://dx.doi.org/10.57182/jbiopestic.9.2.189-195.
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The present study is aimed at evaluating the pathological changes in various tissues of Oreochromis mossambicus exposed to the neem based pesticide achook. The LC50 value obtained after 96 hrs was 0.105 ppm and 1/5th of LC50 value i.e., 0.021 ppm was taken as sublethal concentration. The fishes were exposed to this sublethal concentration for a period of 42-days. Fishes were dissected at the end of 7th day and 42nd day of exposure and the gill, liver and intestine were collected from exposed fishes and control group. Tissues were processed and sectioned at 4µm and stained with Haematoxylin-Eosin. The histological changes observed were mild on 7th day but became severe by 42nd day. The pathological changes in gills of exposed fishes include shrunken and fused gill lamellae, inflammatory cells in the primary and secondary gill lamellae. Exposed liver showed lesions consisting of vacuolar degeneration and disruption of hepatocytes. The changes found in intestine were vacuolar degeneration and disruption of epithelial cells of villi, ruptured and shapeless villi. The histology of tissues from control fishes were normal.
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Ali, Mayyadah Mahmood, et Tavga Ahmed Aziz. « Toxic Effect of Platinum Compounds : Molecular Mechanisms of Toxicity ». Al-Rafidain Journal of Medical Sciences ( ISSN : 2789-3219 ) 1 (30 octobre 2021) : 81–88. http://dx.doi.org/10.54133/ajms.v1i.32.
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Despite their effectiveness as a crucial component of combination chemotherapy regimens against solid tumors, platinum compounds have many serious side effects that limit their use. This review article focuses on the various toxic effects of platinum compounds in cancer patients and the mechanisms of toxicity associated with each of these toxic effects. It also describes the future directions for developing novel platinum compounds, using both animal and human studies. The reference lists of relevant publications were included after searching the Google and Google Scholar databases, PubMed, and scientific journals. It focuses primarily on trials that were published between 2005 and 2020. Platinum-based medicines, as a soft nucleophile, can freely bind to peptides and proteins containing sulfur residues from thiol-containing amino acids like cysteine and methionine, as well as the antioxidant peptide glutathione. Platinum medicines, on the other hand, are primarily directed at nuclear DNA. Platinum medicines bind to normal cells as well as malignant cells, particularly those in fast growing tissues, causing a variety of dangerous side effects. Fast-growing tissues such as the mucous membranes of the mouth, throat, stomach, and intestines, bone marrow, and hair follicles can be damaged by cytotoxic chemotherapy drugs, resulting in gastrointestinal toxicities, myelosuppression, and hair loss. Platinum compounds also cause nephrotoxicity and hepatotoxicity, which are well-known side effects. Current platinum-based chemotherapy treatments have been restricted in the last decade, prompting a search for novel platinum-based medications with mechanisms of action distinct from those of existing chemotherapeutics.
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ENAGBONMA, B. J., S. EKAYE, P. TAWARI-FUFEYIN et O. OSEMWEGIE. « HISTO-AMELIORATIVE EFFECT OF PLEUROTUS TUBERREGIUM AGAINST LEAD INDUCED HEART, SPLEEN AND LOWER GUT DAMAGE IN ALBINO RAT ». Nigerian Journal of Life Sciences (ISSN : 2276-7029) 5, no 1 (25 mars 2022) : 74–84. http://dx.doi.org/10.52417/njls.v5i1.210.
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This study evaluates ameliorative effect of Pleurotus tuberregium on the effects of lead (Pb) using different concentrations of Pleurotus tuberregium /growers mash feed mixture in 90 Albino rats divided into six groups with three replicates (with 5 rats per group) for 21days pre-experimental stage for proper acclimatization. There after all the experimental groups were exposed to 0.1 g/l of lead daily for 21days. At the end of exposure period, lead salt was discontinued for 21and 42days post-experimental stage. Tissues of heart, spleen and lower gut were then collected and subsequently analyzed for the structural changes at every 21days interval. The tissues of the pre-experimental stages showed normal tissues as those of the control except in the lower gut which showed ileal mucosa with chronic inflammatory cell infiltration and muscularis propria. However, the experimental groups, showed observable damages to the tissues of heart (with transmural oedoma and myocardial degeneration, interstitial haemorrhage and coronary vascular hypertrophy), spleen(with focal activated follicles and sinus hyperplasia.) and lower gut (have ileal mucosa with focal atrophy and normal muscularis propria) which improved in the post experimental stages after 21 and 42 days with increased Pleurotus tuberregium content in the feed. The results of this study demonstrated that P .tuberregium may ameliorate lead toxicity in heart, spleen and lower gut tissues
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Usui, Tatsuya, Masashi Sakurai, Shuhei Enjoji, Hideyoshi Kawasaki, Koji Umata, Takashi Ohama, Nobuyuki Fujiwara et al. « Establishment of a Novel Model for Anticancer Drug Resistance in Three-Dimensional Primary Culture of Tumor Microenvironment ». Stem Cells International 2016 (2016) : 1–10. http://dx.doi.org/10.1155/2016/7053872.
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Tumor microenvironment has been implicated in tumor development and progression. As a three-dimensional tumor microenvironment model, air liquid interface (ALI) organoid culture from oncogene transgenic mouse gastrointestinal tissues was recently produced. However, ALI organoid culture system from tissues of colorectal cancer patients has not been established. Here, we developed an ALI organoid model from normal and tumor colorectal tissues of human patients. Both organoids were successfully generated and showed cystic structures containing an epithelial layer and surrounding mesenchymal stromal cells. Structures of tumor organoids closely resembled primary tumor epithelium. Expression of an epithelial cell marker, E-cadherin, a goblet cell marker, MUC2, and a fibroblast marker, vimentin, but not a myofibroblast marker, α-smooth muscle actin (SMA), was observed in normal organoids. Expression of E-cadherin, MUC2, vimentin, and α-SMA was observed in tumor organoids. Expression of a cancer stem cell marker, LGR5 in tumor organoids, was higher than that in primary tumor tissues. Tumor organoids were more resistant to toxicity of 5-fluorouracil and Irinotecan than colorectal cancer cell lines, SW480, SW620, and HCT116. These findings indicate that ALI organoid culture from colorectal cancer patients may become a novel model that is useful for examining resistance to chemotherapy in tumor microenvironment.
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Alshammari, Fatemah O. F. O., Yousef M. Al-saraireh, Ahmed M. M. Youssef, Yahya M. Al-Sarayra et Hamzeh Mohammad Alrawashdeh. « Cytochrome P450 1B1 Overexpression in Cervical Cancers : Cross-sectional Study ». Interactive Journal of Medical Research 10, no 4 (12 octobre 2021) : e31150. http://dx.doi.org/10.2196/31150.
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Background Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. Objective The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme’s relationship with several clinicopathological features. Methods Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. Results CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). Conclusions The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations.
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Rohilla, Seema, Harish Dureja et Vinay Chawla. « Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells : A Review ». Current Cancer Drug Targets 19, no 10 (23 décembre 2019) : 765–81. http://dx.doi.org/10.2174/1568009619666190326120457.
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Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.
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Jia, William W. G., Jiren Tan, Gary J. Redekop et James H. Goldie. « Toxicity studies in thymidine kinase—deficient herpes simplex virus therapy for malignant astrocytoma ». Journal of Neurosurgery 85, no 4 (octobre 1996) : 662–66. http://dx.doi.org/10.3171/jns.1996.85.4.0662.
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✓ Previous studies have shown that genetically engineered thymidine kinase (tk)—defective herpes simplex virus type 1 (HSV-1) can effectively and selectively destroy gliomas in animal models. The consequences of viral infection and tumor regression must be characterized before this therapy can be applied in human trials. To study the potential for long-term toxicity, immunocompetent rats harboring 9L gliosarcomas were injected intratumorally with a tk—defective HSV-1, KOS-SB, at titers that previously have been demonstrated to cause tumor regression. In animals surviving 3 months or longer following viral treatment, there was no evidence of persistent infection or inflammation in peritumoral brain tissue or in remote systemic organs studied with routine histological and immunocytochemical analyses. Polymerase chain reaction using primers specific for HSV-1 detected HSV-1 DNA in peritumoral tissue only in animals sacrificed within 3 months of viral injection. There was no evidence of HSV-1 DNA in systemic tissues at any time after treatment. We conclude that stereotactic intratumoral injection of tk—deficient HSV can be attempted for the treatment of brain tumors without risk of systemic infection or significant toxicity to normal brain or remote proliferating tissues.
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Gewaily, Mahmoud S., Safaa E. Abdo, Eman M. Moustafa, Marwa F. AbdEl-kader, Ibrahim M. Abd El-Razek, Mohamed El-Sharnouby, Mohamed Alkafafy et al. « Dietary Synbiotics Can Help Relieve the Impacts of Deltamethrin Toxicity of Nile Tilapia Reared at Low Temperatures ». Animals 11, no 6 (15 juin 2021) : 1790. http://dx.doi.org/10.3390/ani11061790.
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The optimal water temperature for the normal growth of Nile tilapia is between 26 and 28 °C, and the toxicity of pesticides is strongly related to water temperature. An alternate approach to augmenting the resistance of fish to ambient water toxicity and low water temperature via synbiotic feeding was proposed. In this study, fish were allocated into four groups with 10 fish in each replicate, where they were fed a basal diet or synbiotics (550 mg/kg) and kept at a suboptimal water temperature (21 ± 2 °C). The prepared diets were fed to Nile tilapia for 30 days with or without deltamethrin (DMT) ambient exposure (15 μg/L). The groups were named control (basal diet without DMT toxicity), DMT (basal diet with DMT toxicity), synbiotic (synbiotics without DMT toxicity), and DMT + synbiotic (synbiotics with DMT toxicity). The results displayed upregulated transcription of catalase, glutathione peroxidase, and interferon (IFN-γ) genes caused by DMT exposure and synbiotic feeding when compared with the controls. Moreover, HSP70 and CASP3 genes displayed increased transcription caused by DMT exposure without synbiotic feeding. However, fish fed with synbiotics showed downregulated HSP70 and CASP3 gene expressions. The transcription of IL-1β and IL-8 genes were also decreased by DMT exposure, while fish fed synbiotics showed upregulated levels. DMT exposure resulted in irregular histopathological features in gills, intestine, spleen, and liver tissues, while fish fed synbiotics showed regular, normal, and protected histopathological images. Our results indicated that dietary synbiotics ameliorated histopathological damages in DMT-exposed tilapia through alleviation of oxidative stress and inflammation as well as enhancing the immunity.
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Wu, Jia-Shing, Chung-Wen Jen, Hsin-Hsuan Chen et Skye Hung-Chun Cheng. « Stereotactic body radiotherapy and checkpoint inhibitor for locally recurrent unresectable nasopharyngeal carcinoma ». BMJ Case Reports 14, no 7 (juillet 2021) : e240806. http://dx.doi.org/10.1136/bcr-2020-240806.
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The treatment of local recurrence of nasopharyngeal carcinoma (NPC) is challenging, and the role of reirradiation is controversial regarding the high risk for severe toxicity. Stereotactic body radiotherapy (SBRT) is a high-precision radiation technique that can spare surrounding normal tissues. Studies have demonstrated the high activity and low toxicity of both SBRT and anti-programmed-cell-death-1 immune checkpoint inhibitors for head and neck cancers. There has been preclinical and clinical evidence suggesting synergy between radiotherapy and checkpoint inhibitors. We report two patients with locally recurrent unresectable rT4 NPC both involving the retro-orbital areas. They received the same treatment with low-dose SBRT (28 Gy in 5 fractions) and pembrolizumab, and showed a remarkable tumour response without untoward radiation toxicity. SBRT plus an immune checkpoint inhibitor may provide a new treatment option for locally recurrent NPC. We propose further investigation with a formal clinical trial.
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Beigi, Fahimeh H., Soheil Fatahian, Sogand Shahbazi-Gahrouei, Daryoush Shahbazi-Gahrouei et Amin Farzadniya. « Assessment of Ploy Dopamine Coated Fe3O4 Nanoparticles for Melanoma (B16-F10 and A-375) Cells Detection ». Anti-Cancer Agents in Medicinal Chemistry 20, no 16 (5 novembre 2020) : 1918–26. http://dx.doi.org/10.2174/1871520620666200513084616.
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Objective: Polydopamine coated iron oxide nanoparticles (Fe3O4@PDA NPs) were synthesized, characterized, and their MR imaging contrast agents and photothermal potency were evaluated on melanoma (B16-F10 and A-375) cells and normal skin cells. To this end, MTT assay, Fe concentration, and MR imaging of both coated and uncoated NPs were assessed in C57BL/6 mice. Methods: Fe3O4 nanoparticles were synthesized using co-precipitation, and coated with polydopamine. The cytotoxicity of Fe3O4 and Fe3O4@PDA NPs on melanoma cells, with different concentrations, were obtained using MTT assay. MR images and Fe concentrations of nanoprobe and nanoparticles were evaluated under in vivo conditions. Results: Findings indicated that uncoated Fe3O4 showed the highest toxicity in animal (B16-F10) cells at 450μg/ml after 72h, while the highest toxicity in human (A-375) cells were observed at 350μg/ml. These nanoparticles did not reveal any cytotoxicity to normal skin cells, despite having some toxicity features in A-375 cells. MR image signals in the tumor were low compared with other tissues. The iron concentration in the tumor was higher than that of other organs. Conclusion: It is concluded that the cytotoxicity of Fe3O4@PDA was found to be significantly lower than uncoated nanoparticles (p <0.001), which allows some positive effects on reducing toxicity. The prepared nanoprobe may be used as a contrast agent in MR imaging.
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He, Huan, Qibin Liao, Chen Zhao, Cuisong Zhu, Meiqi Feng, Zhuoqun Liu, Lang Jiang et al. « Conditioned CAR-T cells by hypoxia-inducible transcription amplification (HiTA) system significantly enhances systemic safety and retains antitumor efficacy ». Journal for ImmunoTherapy of Cancer 9, no 10 (octobre 2021) : e002755. http://dx.doi.org/10.1136/jitc-2021-002755.
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BackgroundHypoxia is a striking feature of most solid tumors and could be used to discriminate tumors from normoxic tissues. Therefore, the design of hypoxia-conditioned Chimeric Antigen Receptor (CAR) T cells is a promising strategy to reduce on-target off-tumor toxicity in adoptive cell therapy. However, existing hypoxia-conditioned CAR-T designs have been only partially successful in enhancing safety profile but accompanied with reduced cytotoxic efficacy. Our goal is to further improve safety profile with retained excellent antitumor efficacy.MethodsIn this study, we designed and constructed a hypoxia-inducible transcription amplification system (HiTA-system) to control the expression of CAR in T (HiTA-CAR-T) cells. CAR expression was determined by Flow cytometry, and the activation and cytotoxicity of HiTA-CAR-T cells in vitro were evaluated in response to antigenic stimulations under hypoxic or normoxic conditions. The safety of HiTA-CAR-T cells was profiled in a mouse model for its on-target toxicity to normal liver and other tissues, and antitumor efficacy in vivo was monitored in murine xenograft models.ResultsOur results showed that HiTA-CAR-T cells are highly restricted to hypoxia for their CAR expression, activation and cytotoxicity to tumor cells in vitro. In a mouse model in vivo, HiTA-CAR-T cells targeting Her2 antigen showed undetectable CAR expression in all different normoxic tissues including human Her2-expresing liver, accordingly, no liver and systemic toxicity were observed; In contrast, regular CAR-T cells targeting Her2 displayed significant toxicity on human Her2-expression liver. Importantly, HiTA-CAR-T cells were able to achieve significant tumor suppression in murine xenograft models.ConclusionOur HiTA system showed a remarkable improvement in hypoxia-restricted transgene expression in comparison with currently available systems. HiTA-CAR-T cells presented significant antitumor activities in absence of any significant liver or systemic toxicity in vivo. This approach could be also applied to design CAR-T cell targeting other tumor antigens.
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Sondel, P. M., J. A. Hank, P. C. Kohler, B. P. Chen, D. Z. Minkoff et J. A. Molenda. « Destruction of autologous human lymphocytes by interleukin 2-activated cytotoxic cells. » Journal of Immunology 137, no 2 (15 juillet 1986) : 502–11. http://dx.doi.org/10.4049/jimmunol.137.2.502.
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Abstract Human and murine lymphocyte populations differentiate into lymphokine activated killer (LAK) cells after in vitro or in vivo exposure to interleukin 2 (IL 2). LAK cells mediate destruction of neoplastic tissue in vitro and have been reported to spare normal tissue. However, systemic toxicity is observed in mice and patients receiving IL 2 infusions. Some aspects of this toxicity are similar to that seen in graft-vs-host disease, suggesting that IL 2 may cause an immune-mediated destruction of normal tissues. We have evaluated this issue by examining the destructive potential of fresh human lymphocytes cultured in media containing highly purified recombinant human IL 2. In the absence of any exogenous antigen or allogeneic stimulating cells, strong proliferative responses were induced after 6 days of exposure to IL 2. Lymphocytes harvested from these 6-day cultures were highly cytotoxic to K562 and Daudi target cells. These IL 2-activated cells were also cytotoxic against autologous and allogeneic normal lymphocyte target cells. This autologous lymphocyte destruction was detected in media containing autologous serum and was directly dependent on the concentration of IL 2 added to the cultures. These studies demonstrate that populations of IL 2-activated lymphocytes, containing LAK activity, can mediate low-level but significant destruction of normal lymphocytes in vitro.
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Zappa, Francesco, Timothy Ward, Ennio Pedrinis, John Butler et Alan McGown. « NAD(P)H:Quinone Oxidoreductase 1 Expression in Kidney Podocytes ». Journal of Histochemistry & ; Cytochemistry 51, no 3 (mars 2003) : 297–302. http://dx.doi.org/10.1177/002215540305100304.
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NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a cytosolic two-electron reductase, and compounds of the quinone family such as mitomycin C are efficiently bioactivated by this enzyme. The observation that DT-diaphorase is highly expressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information about the cell-specific expression of DT-diaphorase, the purpose of this study was to map the distribution of this enzyme in normal human tissues. Fifteen tissue samples from normal human kidney were analyzed for expression of DT-diaphorase by immunohistochemistry (two-step indirect method). We found a specific high expression of DT-diaphorase in glomerular visceral epithelial cells (podocytes). These results suggest that a high expression of DT-diaphorase in podocytes could play a major role in the pathogenesis of renal toxicity and mitomycin C-induced hemolytic uremic syndrome, in which injury to the glomerular filtration mechanism is the primary damage, leading to a cascade of deleterious events including microangiopathic hemolytic anemia and thrombocytopenia. This observation has potential therapeutic implications because the DT-diaphorase metabolic pathway is influenced by many agents, including drugs, diet, and environmental cell factors such as pH and oxygen tension.
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Naz, Kiran, Muhammad Rashid Khan, Naseer Ali Shah, Saadia Sattar, Farah Noureen et Madeeha Latif Awan. « Pistacia chinensis : A Potent Ameliorator of CCl4Induced Lung and Thyroid Toxicity in Rat Model ». BioMed Research International 2014 (2014) : 1–13. http://dx.doi.org/10.1155/2014/192906.
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In the current study protective effect of ethanol extract ofPistacia chinensisbark (PCEB) was investigated in rats against CCl4induced lung and thyroid injuries. PCEB dose dependently inhibited the rise of thiobarbituric acid-reactive substances, hydrogen peroxide, nitrite, and protein content and restored the levels of antioxidant enzymes, that is, catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase,γ-glutamyl transpeptidase, and quinone reductase in both lung and thyroid tissues of CCl4treated rats. Decrease in number of leukocytes, neutrophils, and hemoglobin and T3and T4content as well as increase in monocytes, eosinophils, and lymphocytes count with CCl4were restored to normal level with PCEB treatment. Histological study of CCl4treated rats showed various lung injuries like rupture of alveolar walls and bronchioles, aggregation of fibroblasts, and disorganized Clara cells. Similarly, histology of CCl4treated thyroid tissues displayed damaged thyroid follicles, hypertrophy, and colloidal depletion. However, PCEB exhibited protective behaviour for lungs and thyroid, with improved histological structure in a dose dependant manner. Presence of three known phenolic compounds, that is, rutin, tannin, and gallic acid, and three unknown compounds was verified in thin layer chromatographic assessment of PCEB. In conclusion,P. chinensisexhibited antioxidant activity by the presence of free radical quenching constituents.