Zeitschriftenartikel: „Subchronic“

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Kudrow, Lee. „Subchronic Cluster Headache“. Headache: The Journal of Head and Face Pain 27, Nr. 4 (April 1987): 197–200. http://dx.doi.org/10.1111/j.1526-4610.1987.hed2704197.x.

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Carnevali, Luca, Evgeny Bondarenko, Andrea Sgoifo, Frederick R. Walker, Geoffrey A. Head, Elena V. Lukoshkova, Trevor A. Day und Eugene Nalivaiko. „Metyrapone and fluoxetine suppress enduring behavioral but not cardiac effects of subchronic stress in rats“. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 301, Nr. 4 (Oktober 2011): R1123—R1131. http://dx.doi.org/10.1152/ajpregu.00273.2011.

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In humans, chronic stressors have long been recognized as potential causes for cardiac dysregulation. Despite this, the underlying mechanistic links responsible for this association are still poorly understood. The purpose of this study was to determine whether exposure to a paradigm of subchronic stress can provoke enduring changes on the heart rate of experimental rats and, if so, to reveal the autonomic and neural mechanisms that mediate these effects. The study was conducted on adult male Sprague-Dawley rats instrumented for telemetric recording of heart rate and locomotor activity. Animals were submitted to a subchronic stress protocol, consisting of a 1-h foot shock session on five consecutive days. Heart rate and locomotor activity were recorded continuously for 3 days before and for 6 days after the subchronic stress period. Subchronic foot shock produced significant and enduring reduction in heart rate both during the dark/active [Δ= −23 ± 3 beats per minute (bpm)] and light/inactive (Δ= −20 ± 3 bpm) phases of the circadian cycle, and a reduction in locomotor activity during the dark/active phase [Δ= −54 ± 6 counts per hour (cph)]. The bradycardic effect of subchronic stress was not related to a reduced locomotion. Selective sympathetic (atenolol) and vagal (methyl-scopolamine) blockades were performed to reveal which autonomic component was responsible for this effect. We found that the fall in heart rate persisted after subchronic stress in animals treated with atenolol (active phase Δ= −16 ± 3 bpm, inactive phase Δ= −19 ± 2 bpm), whereas vagal blockade with scopolamine transiently prevented this effect, suggesting that the bradycardia following subchronic stress was predominantly vagally mediated. Fluoxetine (selective serotonin reuptake inhibitor) and metyrapone (inhibitor of corticosterone synthesis) treatments did not affect heart rate changes but prevented the reduction in locomotion. We conclude that subchronic stress exposure in rats reduces heart rate via a rebound in vagal activation and that this effect is serotonin- and corticosterone-independent.

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Landreth, K., U. Simanaviciute, J. Fletcher, B. Grayson, R. A. Grant, M. H. Harte und J. Gigg. „Dissociating the effects of distraction and proactive interference on object memory through tests of novelty preference“. Brain and Neuroscience Advances 5 (Januar 2021): 239821282110031. http://dx.doi.org/10.1177/23982128211003199.

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Encoding information into memory is sensitive to distraction while retrieving that memory may be compromised by proactive interference from pre-existing memories. These two debilitating effects are common in neuropsychiatric conditions, but modelling them preclinically to date is slow as it requires prolonged operant training. A step change would be the validation of functionally equivalent but fast, simple, high-throughput tasks based on spontaneous behaviour. Here, we show that spontaneous object preference testing meets these requirements in the subchronic phencyclidine rat model for cognitive impairments associated with schizophrenia. Subchronic phencyclidine rats show clear memory sensitivity to distraction in the standard novel object recognition task. However, due to this, standard novel object recognition task cannot assess proactive interference. Therefore, we compared subchronic phencyclidine performance in standard novel object recognition task to that using the continuous novel object recognition task, which offers minimal distraction, allowing disease-relevant memory deficits to be assessed directly. We first determined that subchronic phencyclidine treatment did not affect whisker movements during object exploration. Subchronic phencyclidine rats exhibited the expected distraction standard novel object recognition task effect but had intact performance on the first continuous novel object recognition task trial, effectively dissociating distraction using two novel object recognition task variants. In remaining continuous novel object recognition task trials, the cumulative discrimination index for subchronic phencyclidine rats was above chance throughout, but, importantly, their detection of object novelty was increasingly impaired relative to controls. We attribute this effect to the accumulation of proactive interference. This is the first demonstration that increased sensitivity to distraction and proactive interference, both key cognitive impairments in schizophrenia, can be dissociated in the subchronic phencyclidine rat using two variants of the same fast, simple, spontaneous object memory paradigm.

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Lavric, A., K. Culjak, D. Tibaut und M. Nemec. „Subchronic toxicity of AmoksiklavR“. Toxicology Letters 95 (Juli 1998): 115. http://dx.doi.org/10.1016/s0378-4274(98)80457-8.

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5

JOHANNSEN, FREDERICK R., und GEORGE J. LEVINSKAS. „Subchronic Toxicity of Tetramethylsuccinonitrile“. Toxicological Sciences 7, Nr. 1 (1986): 41–48. http://dx.doi.org/10.1093/toxsci/7.1.41.

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JOHANNSEN, F. „Subchronic toxicity of tetramethylsuccinonitrile“. Fundamental and Applied Toxicology 7, Nr. 1 (Juli 1986): 41–48. http://dx.doi.org/10.1016/0272-0590(86)90195-8.

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7

Micovic, Zarko, Sanja Kostic, Slavica Mutavdzin, Aleksa Andrejevic, Aleksandra Stamenkovic, Mirjana Colovic, Danijela Krstic et al. „The effects of acutely and subchronically applied DL-methionine on plasma oxidative stress markers and activity of acetylcholinesterase in rat cardiac tissue“. Vojnosanitetski pregled 77, Nr. 2 (2020): 165–73. http://dx.doi.org/10.2298/vsp171213055m.

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Background/Aim. Chronically induced hypermethioninemia leads to hyperhomocysteinemia which causes oxidative stress, atherogenesis, neurodegeneration and cancer. However, little is known about the acute and subchronic effects of DL-methionine (Met). The aim of study was to assess the effects of acutely and subchronically applied Met on oxidative stress parameters in rat plasma [enzymes: catalase (CAT), glutathione peroxidise (GPx), superoxide dismutase (SOD) and index of lipid peroxidation, malondialdehyde (MDA)], and acetylcholinesterase (AChE) activity in rat cardiac tissue. Methods. The enzymes activities, as well as MDA concentration were evaluated following acute (n = 8) and subchronic (n = 10) application of Met [i.p. 0.8 mmoL/kg body weight (b.w.) in a single dose in the acute overload or daily during three weeks in the subchronic overload]. The same was done in the control groups following application of physiological solution [i.p. 1 mL 0.9% NaCl (n = 8) in the acute overload and 0.1?0.2 mL 0.9% NaCl, daily during three weeks (n =10) in the subchronic overload]. Tested parameters were evaluated 60 minutes after application in acute experiments and after three weeks of treatment in subchronic experiments. Results. There were no difference in homocysteine values between the groups treated with Met for three weeks and the control group. Met administration significantly increased the activity of CAT and GPx after 1 h compared to the control group (p = 0.008 for both enzymes), whereas the activity of SOD and MDA concentrations were unchanged. Subchronically applied Met did not affect activity of antioxidant enzymes and MDA level. AChE activity did not show any change in rat cardiac tissue after 1 h, but it was significantly decreased after the subchronic treatment (p = 0.041). Conclusion. Results of present research indicate that Met differently affects estimated parameters during acute and subchronic application. In the acute treatment Met mobilizes the most part of antioxidant enzymes while during the subchronic treatment these changes seems to be lost. On the contrary, the acute Met overload was not sufficient to influence on the AChE activity, while longer duration of Met loading diminished function of the enzyme. These findings point out that methionine can interfere with antioxidant defense system and cholinergic control of the heart function.

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Vyas, Archana, Heera Ram, Ashok Purohit und Rameshwar Jatwa. „Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats“. Journal of Pharmaceutics 2016 (12.04.2016): 1–9. http://dx.doi.org/10.1155/2016/6585430.

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Aspirin (acetylsalicylic acid) is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte) count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60-day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry.

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Tung, Tran Thanh, Dau Thuy Duong, Pham Thi Thuy Minh, Nguyen Thu Hien und Dinh Thi Thu Hang. „Evaluation of acute and subchronic toxicities of “Phuong Dong Dai Trang” tablets in experimental animals“. Tạp chí Nghiên cứu Y học 141, Nr. 5 (30.06.2021): 29–38. http://dx.doi.org/10.52852/tcncyh.v141i5.210.

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The study aimed to evaluate the acute and subchronic toxicities of “Phuong Dong Dai Trang” tablets through oral administration using experimental animal models. Acute toxicity in Swiss mice was determined using the Litchfield Wilcoxon method. The subchronic toxicity in Wistar rats was evaluated according to WHO and OECD’s recommendation with oral doses of 4.68 g/kg/day (equivalent to recommended human dose) and 14.04 g/kg/day (3 times the recommended human dose) for 4 consecutive weeks. In terms of acute toxicity, “Phuong Dong Dai Trang” tablets did not express acute toxicity in mice at the highest dose used (232.14 g materials/kg). In terms of the subchronic toxicity, after oral administration of “Phuong Dong Dai Trang” tablets, hematological parameters, hepato - renal functions, and microscopic images of liver and kidney were unchanged in the treatment group compared to the control group. In conclusion, “Phuong Dong Dai Trang” tablets did not produce acute and subchronic toxicities in Swiss mice and Wistar rats.

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Fukuyama, Kouji, und Motohiro Okada. „Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43“. International Journal of Molecular Sciences 22, Nr. 11 (25.05.2021): 5623. http://dx.doi.org/10.3390/ijms22115623.

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Recently, accumulating preclinical findings suggest the possibility that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of schizophrenia and affective disorder. Therefore, to explore the novel mechanisms of mood-stabilizing effects associated with tripartite synaptic transmission, the present study determined the effects of mood-stabilizing antipsychotics, clozapine (CLZ), quetiapine (QTP) and brexpiprazole (BPZ), on the astroglial l-glutamate release and expression of connexin43 (Cx43) in the astroglial plasma membrane using cortical primary cultured astrocytes. Neither acute (for 120 min) nor subchronic (for 7 days) administrations of CLZ, QTP and BPZ affected basal astroglial l-glutamate release, whereas both acute and subchronic administration of CLZ, QTP and BPZ concentration-dependently enhanced astroglial l-glutamate release through activated hemichannels. Subchronic administration of therapeutic-relevant concentration of valproate (VPA), a histone deacetylase inhibiting mood-stabilizing antiepileptic drug, enhanced the stimulatory effects of therapeutic-relevant concentration of CLZ, QTP and BPZ on astroglial l-glutamate release through activated hemichannel. Subchronic administration of therapeutic-relevant concentration of CLZ, QTP and BPZ did not affect Cx43 protein expression in the plasma membrane during resting stage. After subchronic administration of VPA, acute and subchronic administration of therapeutic-relevant concentrations of CLZ increased Cx43 protein expression in the plasma membrane. Both acute administrations of therapeutic-relevant concentrations of QTP and BPZ did not affect, but subchronic administrations enhanced Cx43 protein expression in the astroglial plasma membrane. Furthermore, protein kinase B (Akt) inhibitor suppressed the stimulatory effects of CLZ and QTP, but did not affect Cx43 protein expression in the astroglial plasma membrane. These results suggest that three mood-stabilizing atypical antipsychotics, CLZ, QTP and BPZ enhance tripartite synaptic glutamatergic transmission due to enhancement of astroglial Cx43 containing hemichannel activities; however, the Cx43 activating mechanisms of these three mood-stabilizing antipsychotics were not identical. The enhanced astroglial glutamatergic transmission induced by CLZ, QTP and BPZ is, at least partially, involved in the actions of these three mood-stabilizing antipsychotics.

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Güleç, Mukaddes, Ahmet Songur, Semsettin Sahin, Oguz A. Ozen, Mustafa Sarsilmaz und Omer Akyol. „Antioxidant enzyme activities and lipid peroxidation products in heart tissue of subacute and subchronic formaldehyde-exposed rats: a preliminary study“. Toxicology and Industrial Health 22, Nr. 3 (April 2006): 117–24. http://dx.doi.org/10.1191/0748233706th248oa.

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Objective: The aim of this experimental study was to evaluate the oxidant/antioxidant status and lipid peroxidation in the heart of rats exposed to formaldehyde (FA) inhalation for four weeks (subacute) or 13 weeks (subchronic) continuously. Methods and results: Sixty Wistar albino rats were divided into six groups randomly (ten in each group). The first and second groups were used as subacute and subchronic control groups. FA gas was generated from paraformaldehyde and pumped to a closed glass chamber. Rats were exposed to atmosphere containing 10 and 20 ppm FA (8 h/day, five days per week) during a four and 13 weeks period. After heart tissues were obtained and homogenized, thiobarbituric acid-reactant substances (TBARS) and nitric oxide (NO) levels, as well as superoxide dismutase (SOD) and catalase (CAT) activities, were measured. There were statistically significant findings in SOD and CAT activities in the study groups compared to the control group. Heart tissue SOD level was increased in the group exposed to subacute 10 and 20 ppm FA inhalation compared to the control group (P≤0.011 and ≤0.0001). In addition, heart tissue SOD level was increased in the group exposed to subchronic 10 and 20 ppm FA inhalation compared to the corresponding control group (P≤0.001). On the other hand, there were statistically significant decreases in CAT activity in subacute 10 and 20 ppm groups compared to the corresponding control group (P≤0.012 and ≤0.039, respectively). Although not significant, TBARS levels were increased in both subacute 10 ppm (P=0.100) and subchronic 20 ppm (P=0.053) groups compared to their corresponding control groups. Tissue NO levels were unchanged upon FA inhalation. In the correlation analyses, a meaningful relationship between SOD and CAT activities in subchronic 10 ppm group (r=-0.685, P≤0.029); SOD activity and TBARS level in subchronic 20 ppm group (r=-0.675, P≤0.032); and CAT activity and NO level in subchronic 20 ppm group (r=-0.810, P≤0.005) were found. Conclusion: From the findings of our study, it can be interpreted that subacute and subchronic FA inhalation may stimulate oxidative stress and thus, some secondary toxic effects in cardiac cells and tissue. This increase in the oxidative stress could not induce lipid peroxidation in the membranous structure of cardiac cells. An increased SOD enzyme activity was thought to be secondary to decreased CAT activity, as a compensation mechanism, preventing heart tissue from destruction induced by FA.

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Belyaev, Valery Anatolyevich, Vladimir Sergeyevich Nikulin, Ruslan Rashidovich Kochkarov, Nikolay Alekseyevich Gvozdetskii und Tatyana Anatolyevna Beloborodenko. „Research of subchronic inhalation toxicity of ozone-air mixture“. Agrarian Scientific Journal, Nr. 3 (16.03.2020): 40–43. http://dx.doi.org/10.28983/asj.y2020i3pp40-43.

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The subchronic inhalation toxicity of the ozone-air mixture obtained on a portable ozone generation device (ozonizer) of its own design was studied. The work investigated the concentration of ozone-air mixture of 1000, 3000 and 5000 ppm. The experiment was carried out, according to the standards for determining subchronic inhalation toxicity of substances, for 90 days, on rats of the Wistar strain. Throughout the experiment, body weight, feed intake were recorded, behavioral activity was evaluated, hematological and biochemical blood parameters were determined. As a result of the study of subchronic inhalation toxicity of the ozone-air mixture, no signs of intoxication were detected in rats, there was no case.

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Chang, Chia-Yu, How-Ran Guo, Wan-Chen Tsai, Kai-Lin Yang, Li-Chuan Lin, Tain-Junn Cheng und Jiunn-Jye Chuu. „Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression“. BioMed Research International 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/159015.

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Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

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Lynch, Barry, Ryan Simon und Ashley Roberts. „Subchronic toxicity evaluation of aloesin“. Regulatory Toxicology and Pharmacology 61, Nr. 2 (November 2011): 161–71. http://dx.doi.org/10.1016/j.yrtph.2011.07.005.

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Valentine, R., A. J. O'Neill, K. P. Lee und G. L. Kennedy. „Subchronic inhalation toxicity of diglyme“. Food and Chemical Toxicology 37, Nr. 1 (Januar 1999): 75–86. http://dx.doi.org/10.1016/s0278-6915(98)00096-9.

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Prieto, Pilar, Cecilia Clemedson, Annarita Meneguz, Walter Pfaller, Ursula G. Sauer und Carl Westmoreland. „3.6. Subacute and Subchronic Toxicity“. Alternatives to Laboratory Animals 33, Nr. 1_suppl (Juli 2005): 109–16. http://dx.doi.org/10.1177/026119290503301s12.

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Andrews, L. S., John J. Clary, J. B. Terrill und Henry F. Bolte. „Subchronic inhalation toxicity of methanol“. Journal of Toxicology and Environmental Health 20, Nr. 1-2 (Januar 1987): 117–24. http://dx.doi.org/10.1080/15287398709530965.

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Curry, Leslie L., und Ashley Roberts. „Subchronic toxicity of rebaudioside A“. Food and Chemical Toxicology 46, Nr. 7 (Juli 2008): S11—S20. http://dx.doi.org/10.1016/j.fct.2008.04.042.

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Coelho, VR, K. Sousa, TR Pires, DKM Papke, CG Vieira, LP de Souza, MB Leal, RVA Schunck, JN Picada und P. Pereira. „Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task“. Human & Experimental Toxicology 35, Nr. 9 (19.07.2016): 958–65. http://dx.doi.org/10.1177/0960327115611970.

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Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.

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Li, Abby A., Jacques P. J. Maurissen, John F. Barnett, John Foss, Les Freshwater, Robert H. Garman, Vanessa L. Peachee, Sandra J. Hong, Donald G. Stump und James S. Bus. „Oral gavage subchronic neurotoxicity and inhalation subchronic immunotoxicity studies of ethylbenzene in the rat“. NeuroToxicology 31, Nr. 3 (Juni 2010): 247–58. http://dx.doi.org/10.1016/j.neuro.2010.02.001.

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Schaeppi, U., und R. E. Fitzgerald. „Practical Procedure of Testing for Neurotoxicity“. Journal of the American College of Toxicology 8, Nr. 1 (Januar 1989): 29–34. http://dx.doi.org/10.3109/10915818909009091.

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In the course of routinely performed subchronic toxicity studies with laboratory rodents, functional neurotoxicity, i.e., behavioral changes, usually are noted first during the daily cageside observations of all animals, Observation and neurologic examination of a few key animals provide a tentative diagnosis. Subsequent automated testing procedures for further characterization and quantifying behavioral changes might include motor activity, startle response, hurdle stepping, and maze behavior. Automated testing serves to assess the no observable effect under conditions of blind testing and provides further refinement of the diagnosis. Behavioral changes should be assessed as early as possible after onset of testing, i.e., during acute tests for mortality and the subsequent subchronic range-finding studies. Subsequent subchronic organ toxicity studies are then carried out by following a validated experimental protocol, including automated testing procedures and appropriate neuropathologic evaluation.

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Eftimov, Miroslav Ts, und StefkaV Valcheva-Kuzmanova. „Investigation of Aronia Melanocarpa Fruit Juice for Sedative-Hypnotic Effects in Rats“. Journal of Biomedical and Clinical Research 11, Nr. 1 (01.07.2018): 77–82. http://dx.doi.org/10.2478/jbcr-2018-0012.

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Summary Aronia melanocarpa fruit juice (AMFJ) has been intensively studied for effects on the central nervous system. The study aimed to investigate AMFJ for possible sedative-hypnotic effects in rats after acute and subchronic administration. Male Wistar rats were treated orally with three doses of AMFJ (2.5, 5.0 and 10.0 ml/kg) either once (acute treatment) or in 30 days (subchronic treatment). Control rats were similarly treated with distilled water. The tests were performed 1 hour after the last AMFJ administration. The possible sedative-hypnotic effects of the juice were investigated in the open field test (OFT) and thiopental-induced sleeping time test. Substances with sedative-hypnotic effects decrease locomotor activity in the OFT and prolong the time of thiopental-induced sleep. The results from the OFT showed that neither the acute, nor the subchronic treatment of rats with all AMFJ doses affected the horizontal and vertical locomotor activity significantly. The two patterns of administration of AMFJ (acute and subchronic) had no significant effect on the duration of thiopental-induced sleep. The lack of effect of AMFJ on locomotor activity and the lack of prolongation of thiopental-induced sleep showed that AMFJ did not display sedative-hypnotic effects in rats.

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Somchit, N., A. R. Norshahida, A. H. Hasiah, A. Zuraini, M. R. Sulaiman und M. M. Noordin. „Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study“. Human & Experimental Toxicology 23, Nr. 11 (November 2004): 519–25. http://dx.doi.org/10.1191/0960327104ht479oa.

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Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, l00 and 200 mg/kg) or subchronic (0, 10, 50 and loo mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.

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Shiroyama, Takashi, Kouji Fukuyama und Motohiro Okada. „Distinct Effects of Escitalopram and Vortioxetine on Astroglial L-Glutamate Release Associated with Connexin43“. International Journal of Molecular Sciences 22, Nr. 18 (16.09.2021): 10013. http://dx.doi.org/10.3390/ijms221810013.

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It has been established that enhancement of serotonergic transmission contributes to improvement of major depression; however, several post-mortem studies and experimental depression rodent models suggest that functional abnormalities of astrocytes play important roles in the pathomechanisms/pathophysiology of mood disorders. Direct effects of serotonin (5-HT) transporter inhibiting antidepressants on astroglial transmission systems has never been assessed in this context. Therefore, to explore the effects of antidepressants on transmission associated with astrocytes, the present study determined the effects of the selective 5-HT transporter inhibitor, escitalopram, and the 5-HT partial agonist reuptake inhibitor, vortioxetine, on astroglial L-glutamate release through activated hemichannels, and the expression of connexin43 (Cx43), type 1A (5-HT1AR) and type 7 (5-HT7R) 5-HT receptor subtypes, and extracellular signal-regulated kinase (ERK) in astrocytes using primary cultured rat cortical astrocytes in a 5-HT-free environment. Both escitalopram and 5-HT1AR antagonist (WAY100635) did not affect basal astroglial L-glutamate release or L-glutamate release through activated hemichannels. Subchronic (for seven days) administrations of vortioxetine and the 5-HT7R inverse agonist (SB269970) suppressed both basal L-glutamate release and L-glutamate release through activated hemichannels, whereas 5-HT1AR agonist (BP554) inhibited L-glutamate release through activated hemichannels, but did not affect basal L-glutamate release. In particular, WAY100635 did not affect the inhibitory effects of vortioxetine on L-glutamate release. Subchronic administration of vortioxetine, BP554 and SB269970 downregulated 5-HT1AR, 5-HT7R and phosphorylated ERK in the plasma membrane fraction, but escitalopram and WAY100635 did not affect them. Subchronic administration of SB269970 decreased Cx43 expression in the plasma membrane but did not affect the cytosol; however, subchronic administration of BP554 increased Cx43 expression in the cytosol but did not affect the plasma membrane. Subchronic vortioxetine administration increased Cx43 expression in the cytosol and decreased it in the plasma membrane. WAY100635 prevented an increased Cx43 expression in the cytosol induced by vortioxetine without affecting the reduced Cx43 expression in the plasma membrane. These results suggest that 5-HT1AR downregulation probably increases Cx43 synthesis, but 5-HT7R downregulation suppresses Cx43 trafficking to the plasma membrane. These results also suggest that the subchronic administration of therapeutic-relevant concentrations of vortioxetine inhibits both astroglial L-glutamate and Cx43 expression in the plasma membrane via 5-HT7R downregulation but enhances Cx43 synthesis in the cytosol via 5-HT1AR downregulation. This combination of the downregulation of 5-HT1AR, 5-HT7R and Cx43 in the astroglial plasma membrane induced by subchronic vortioxetine administration suggest that astrocytes is possibly involved in the pathophysiology of depression.

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RE, T. „A subchronic, teratologic, and dominant lethal study of 2-methylresorcinol in rats I. Subchronic toxicity“. Fundamental and Applied Toxicology 7, Nr. 2 (August 1986): 287–92. http://dx.doi.org/10.1016/0272-0590(86)90158-2.

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Harikumar, Kuzhuvelil B., Aranjany M. Jesil, Mandumpal C. Sabu und Ramadasan Kuttan. „A Preliminary Assessment of the Acute and Subchronic Toxicity Profile of Phase2: An α-Amylase Inhibitor“. International Journal of Toxicology 24, Nr. 2 (März 2005): 95–102. http://dx.doi.org/10.1080/10915810590936364.

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Phase2®, which has been reported to reduce body weight by its inhibition of α-amylase, was evaluated for toxicity in young adult male and female Wistar rats (10 animals/dose group). Evaluations included mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions as well as hematological, biochemical, and histopathological analyses. Acute toxicity was determined after a single dose of Phase2 by oral gavage at doses of 5.0, 1.0, and 0.5 g/kg body weight. Animals were sacrificed on fourteen days after Phase2 administration. Subchronic toxicity was determined by administering Phase2 daily for 90 days to rats, at doses of 1.0, 0.5, and 0.2 g/kg body weight. These animals were sacrificed on day 90. Acute and subchronic administration of Phase2 did not produce any adverse reactions or any significant change in the loss of body weight as compared to untreated controls, organ weight, and mortality. Administration of Phase2 did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Subchronic administration produced a reduction in the food consumption after 77 days (1.0 g/kg body weight). These data indicate that acute and subchronic administration of Phase2 did not produce any toxicity to rats as evident from weight change, mortality, and limited biochemical and histopathological analyses.

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Lent, Emily May, Lee C. B. Crouse und Shannon M. Wallace. „Oral Toxicity of 2,4-Dinitroanisole in Rats“. International Journal of Toxicology 35, Nr. 6 (07.10.2016): 692–711. http://dx.doi.org/10.1177/1091581816670321.

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Subacute and subchronic studies were conducted to assess the toxicity of 2,4-dinitroanisole (DNAN) and to provide information important for protecting the health of military and civilian personnel. In the subchronic study, male and female Sprague-Dawley rats were dosed with DNAN via oral gavage at 0, 1.25, 5, 20, and 80 mg/kg/d. Likely owing to its conversion to 2,4-dinitrophenol, an inhibitor of energy homeostasis, DNAN caused an apparent increase in metabolism, leading to reduced feed efficiency ratios and body mass gains in males. Anemia, splenic enlargement, hemosiderosis, and extramedullary hematopoiesis indicated blood as a target organ, with females more sensitive than males. The DNAN was a testicular toxicant, causing decreased mass of testes and epididymides, as well as degeneration and atrophy of testicular seminiferous tubules and epididymal aspermia. Stereotypical behavior in males, gait irregularities, and cerebellar lesions indicated that DNAN is neurotoxic. Splenic enlargement, anemia, testicular toxicity, and neurotoxicity occurred only at or near lethal doses in the subchronic study.

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Lavric, A., K. Culjak, D. Tibaut, M. Nemec und A. Stalc. „Subchronic toxicity of substance LK-404“. Toxicology Letters 88 (Oktober 1996): 100. http://dx.doi.org/10.1016/s0378-4274(96)80361-4.

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Goldsmith, L. „Acute and subchronic toxicity of sucralose“. Food and Chemical Toxicology 38 (Juli 2000): 53–69. http://dx.doi.org/10.1016/s0278-6915(00)00028-4.

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Janaki, B., und R. B. Sashidhar. „Subchronic(90-day)ToxicityStudyinRatsFed gumKondagogu(Cochlospermumgossypium)“. Food and Chemical Toxicology 38, Nr. 6 (Juni 2000): 523–34. http://dx.doi.org/10.1016/s0278-6915(00)00037-5.

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Johannsen, Frederick R., und George J. Levinskas. „Acute and subchronic toxicity of tetramethylcyclohexanes“. Journal of Applied Toxicology 7, Nr. 4 (August 1987): 245–48. http://dx.doi.org/10.1002/jat.2550070404.

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Sung, Jae Hyuck, Jun Ho Ji, Jung Duck Park, Jin Uk Yoon, Dae Sung Kim, Ki Soo Jeon, Moon Yong Song et al. „Subchronic Inhalation Toxicity of Silver Nanoparticles“. Toxicological Sciences 108, Nr. 2 (25.11.2008): 452–61. http://dx.doi.org/10.1093/toxsci/kfn246.

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Culjak, K. „Subchronic Toxicity of Substance Lek 8829“. Toxicology Letters 78 (August 1995): 52. http://dx.doi.org/10.1016/03784-2749(59)4824z-.

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Kim, Yong Soon, Moon Yong Song, Jung Duck Park, Kyung Seuk Song, Hyeon Ryol Ryu, Yong Hyun Chung, Hee Kyung Chang et al. „Subchronic oral toxicity of silver nanoparticles“. Particle and Fibre Toxicology 7, Nr. 1 (2010): 20. http://dx.doi.org/10.1186/1743-8977-7-20.

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Sung, Jae, Jun Ji, Jung Park, Moon Song, Kyung Song, Hyeon Ryu, Jin Yoon et al. „Subchronic inhalation toxicity of gold nanoparticles“. Particle and Fibre Toxicology 8, Nr. 1 (2011): 16. http://dx.doi.org/10.1186/1743-8977-8-16.

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Lavrič, A., D. Tibaut, K. Čuljak und M. Nemec. „Subchronic toxicity of substance lek 8829“. Toxicology Letters 78 (August 1995): 52. http://dx.doi.org/10.1016/0378-4274(95)94823-y.

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Chin, T. W. F., M. Spino, S. M. MacLeod, W. A. Mahon und S. J. Soldin. „Pharmacokinetics of cimetidine after subchronic administration“. European Journal of Clinical Pharmacology 30, Nr. 6 (1986): 741–44. http://dx.doi.org/10.1007/bf00608228.

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Runge, Val M., Thomas J. Kuehl, Carney B. Jackson und Elissa A. Estrada. „Subchronic Toxicity of the Gadolinium Chelates“. Academic Radiology 12, Nr. 5 (Mai 2005): S6—S9. http://dx.doi.org/10.1016/j.acra.2005.02.015.

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Frangež, Robert, Marjan Kosec, Bojan Sedmak, Katarina Beravs, Franci Demsar, Polona Juntes, Milan Pogačnik und Dušan Šuput. „Subchronic liver injuries caused by microcystins“. Pflügers Archiv - European Journal of Physiology 440, S1 (Januar 2000): R103—R104. http://dx.doi.org/10.1007/s004240000023.

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Belemnaba, Lazare, Madi Soubeiga, Geoffroy G. Ouédraogo, Tata Kadiatou Traoré, Mathieu Nitiéma, Sylvain Ilboudo, B. Mohamed Belemlilga et al. „Antioxidant properties and subchronic toxicity of the standardized extract of LAMIC, a phytomedicine prototype based on aqueous extracts from trunk bark of Lannea microcarpa Engl and K. Krause“. Journal of Drug Delivery and Therapeutics 9, Nr. 5 (15.09.2019): 1–8. http://dx.doi.org/10.22270/jddt.v9i5.3285.

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Aims: This study investigated the antioxidant activity and the 90 days subchronic toxicity of the standardized LAMIC phytomedicine prototype based on aqueous extracts from Lannea microcarpa trunk bark. Methods: Three spectrophotometric methods were used to evaluated the antioxidant activity of LAMIC which were 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical, 2,2’-azinobis(3-ethylbenzolin-6-sulphonate) (ABTS) radical scavenging assays and ferric reducing antioxidant power (FRAP) assays. For the standardized LAMIC subchronic toxicity study, male and female Wistar rats were used by daily oral administration at doses of 500, 1000 and 1500 mg/kg bw consecutively for 90 days. Results: The LAMIC extract exhibit better inhibitory activity against DPPH radical than ABTS radical with respective IC50 values of 45.38±3.21 µg/mL and 66.45±18.76 µg/mL, while FRAP assay exhibit antioxidant activity of 211.34±15.92 mmol EAA/g. Subchronic oral administration of LAMIC was well-tolerated at all tested doses. No behavioral and physiological changes and mortality were observed. The LAMIC extract did not present any impact on general hematological parameters and biochemical parameters. Moreover, no significant changes were raised in organ and body weight of treated groups compared to the Control group. Conclusion: These results support that LAMIC prototype was a valuable source of natural antioxidants and no toxicity was associated to its long terms oral consumption in rats indicating a potential application as a cardiovascular protective formulation. Keywords: LAMIC–Lannea microcarpa–Standardization–Antioxidant–Subchronic toxicity.

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Asiedu-Gyekye, Isaac Julius, Seidu Abdulai Mahmood, Charles Awortwe und Alexander Kwadwo Nyarko. „A Preliminary Safety Evaluation of Polyhexamethylene Guanidine Hydrochloride“. International Journal of Toxicology 33, Nr. 6 (29.10.2014): 523–31. http://dx.doi.org/10.1177/1091581814553036.

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Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD50 for PHMGH was estimated to be 600 mg/kg (ie LC50 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD50) of 600 mg/kg was accompanied by signs of neurotoxicity. Haematological and biochemical parameters of subchronic toxicity studies were non-significant. Subchronic doses of 0.006 mg/kg, 0.012 mg/kg and 0.036 mg/kg were administered. 20% of the animals at a dose of 0.006 mg/kg and 0.036 mg/kg showed mild degrees of hydropic changes in proximal tubules while 10% of animals at all the doses had their liver tissues showing local areas of mild pericentral hepatocytes degeneration. PHMGH did not produce any major organ defect with regard to the kidney, heart, and liver. The LD50 was much higher than the recommended dosage by a factor of about 50,000. The recommended residual concentration is far less than the median lethal dose using rats as test subjects. These results could serve as a basis for investigating the full toxicological profile if it is to be used for the treatment of raw water to make it potable.

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Sasiarini, Laksmi, Aktaruddin Arief Santoso und Djoko Wahono Soeatmadji. „The Impact of Subchronic Soybean Milk and Genistein Supplementation on Pancreatic Fatty Infiltrations of Sprague Dawley Male Mice“. Clinical and Research Journal in Internal Medicine 1, Nr. 2 (11.11.2020): 79–87. http://dx.doi.org/10.21776/ub.crjim.2020.001.02.4.

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Isoflavones (genistein, daidzein) on soybean milk have phytoestrogenic properties. In Asia, the blood phytoestrogen levels can reach 160 ng/ml (80 times higher than Western). This may potentially disrupt endocrine functions regarding its binding with estrogen receptors.. Since the function and distribution of adipose tissues are regulated by estrogen receptors, the reduction of estrogen receptor-α(ERα) results in ectopic fats distribution around visceral tissues, such as the pancreas. Aim: To investigate the impact of subchronic soybean milk and genistein supplementation on pancreatic fatty infiltrations in mice. Methods: The experiment used 35 Sprague dawley male mice under 7 treatment groups within 60 days: negative control with standard rationed food, 3 groups with a variable dose of soybean milk: 100 mg, 200 mg, and 400 mg, and 3 groups with a variable dose of genistein: 0.4 mg, 0.8 mg, and 1.6 mg. Histological measurements on the level of pancreatic fatty infiltrations were conducted after. Analyses used Kruskal-Wallis and post-hoc Mann-Whitney. Results: Medium to a high level of pancreatic fatty infiltrations were found at the control group while there is a decreasing trend on the level of pancreatic fatty infiltrations on groups with soybean milk and subchronic genistein compared with the control group, proportional to higher dosage supplementation. The reduction of pancreatic fatty infiltration levels on groups with soybean milk and subchronic genistein supplementation is not statistically significant compared to control. Conclusion: Supplementation of soybean milk and subchronic genistein do not significantly reduce the levels of pancreatic fatty infiltrations in Sprague dawley male mice.

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Santiago-Rodríguez, Efraín, Brenda Estrada-Zaldívar und Elba Zaldívar-Uribe. „Effects of Dark Chocolate Intake on Brain Electrical Oscillations in Healthy People“. Foods 7, Nr. 11 (08.11.2018): 187. http://dx.doi.org/10.3390/foods7110187.

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Dark chocolate is rich in flavonoids that can have effects on body composition and cognitive performance. The aim of this study was to analyze the effects of acute and subchronic chocolate intake on electrical brain oscillations. A study with 20 healthy subjects (mean age of 24.15 years) and a control group with five subjects (mean age of 23.2 years) was carried out. In the acute effect study, the subjects’ intake was dark chocolate (103.72 mg/kg of body weight) rich in flavonoids and low in calories as in fasting. In the control group, the subjects intake was only low-calorie milk. For the subchronic effect, a daily dose of dark chocolate was given for eight days. The baseline electroencephalogram (EEG) was recorded before dark chocolate intake; at 30 min, the second EEG was carried out; on the eighth day, the third and fourth EEGs were performed before and after the last intake. In acute and subchronic intake, Delta Absolute Power (AP) decrease was observed in most brain regions (p < 0.05), except in the right fronto-centro-temporal regions. In the Theta band, there was a generalized decrease of the AP of predominance in the left fronto-centro-temporal regions. In contrast, an increase in AP was observed in the temporo-occipital regions in the Alpha band, and in the right temporal and parieto-occipital regions in the Beta band. The control group did not have significant changes in brain oscillations (p > 0.05). We concluded that acute and subchronic chocolate intake decreased the Delta and Theta AP and increased Alpha and Beta AP in most brain regions.

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Aslanian, Milena A., Larisa A. Bobrytska, Natalya L. Bereznyakova, Oleg S. Shpychak, Vita I. Hrytsenko, Tamara A. Germanyuk und Tatiana I. Ivko. „Biochemical research of hepatoprotective activity of Lavaflam tablets in rats with subchronic hepatitis“. Current Issues in Pharmacy and Medical Sciences 33, Nr. 1 (01.03.2020): 10–13. http://dx.doi.org/10.2478/cipms-2020-0003.

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AbstractLiver damage is a common problem all over the world. To optimize the drug provision in the limited financing of the Health Care System, it is necessary to develop new drugs with hepatoprotective properties that are highly effective and of low cost. That is why we developed the original drug Lavaflam. Lavaflam is a combination of the following substances: dry concentrate of Helichrysum arenarium and Lavender oil. The purpose of the research was to assess the biochemical evidence of the hepatoprotective properties of the drug Lavaflam on the experimental model of subchronic hepatitis in rats. Construction of an experimental model of subchronic hepatitis in rats, comparison of hepatoprotective properties of Lavaflam and Carsil preparations on the basis of biochemical research. The subject of the study was to determine the hepatoprotective properties of Lavaflam tablets. Experimental subchronic hepatitis induced in rats by way of intragastrical introduction of tetrachlormethane. The study drug Lavaflam in this experimental model of subchronic tetrachlormethane hepatitis in rats showed a positive effect on oxidant processes by increasing the compensatory mechanisms of antioxidant systems; inhibiting free radical pathology; having positive effect on the processes of biliary excretion, cholestasis, reduction of infiltrative, destructive and inflammatory process in the liver; decreasing the cytolytic process; restoring the structure of the membrane components of hepatocytes; stabilizing and enhancing functional activity of the liver; restoring its protein-synthetic function; and increasing the ability of the drug Lavaflam to restore metabolic and liver damage.As a result of the performed biochemical study of the hepatoprotective action of Lavaflam, it has been found that in the developed drug Lavaflam, the level of hepatoprotective action corresponds with the reference drug Carsil.

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Roursgaard, Martin, Keld A. Jensen, Steen S. Poulsen, Niels-Erik V. Jensen, Lars K. Poulsen, Maria Hammer, Gunnar D. Nielsen und Søren T. Larsen. „Acute and Subchronic Airway Inflammation after Intratracheal Instillation of Quartz and Titanium Dioxide Agglomerates in Mice“. Scientific World JOURNAL 11 (2011): 801–25. http://dx.doi.org/10.1100/tsw.2011.67.

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This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compounds were the two micro-size reference quartzes, SRM1878a and DQ12, a micro- and nano-size rutile titanium dioxide (TiO2), a nano-size anatase, and an amorphous TiO2. Particles were administered by a single i.t. instillation in mice at a fixed dose of 5, 50, and 500 μg, respectively. Inflammation was evaluated from the bronchoalveolar lavage fluid (BALF) content of inflammatory cells, the cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), as well as from lung histology. Evaluations were at 24 h (acute effects) and 3 months (subchronic effects) after instillations. Both types of quartz induced a dose-dependent acute increase of neutrophils, IL-6, and total protein in BALF. Limited subchronic inflammation was observed. All types of TiO2induced a dose-dependent acute increase of neutrophils in BALF. In the acute phase, micro- and nano-size rutile and nano-size amorphous TiO2induced elevated levels of IL-6 and total protein in BALF at the highest dose. At the nano-size rutile and amorphous TiO2, subchronic lung inflammation was apparent from a dose-dependent increase in BALF macrophages. Histology showed little inflammation overall. The two types of quartz showed virtually similar inflammatory effects. Nearly similar effects were observed for two sizes of rutile TiO2. Differences were seen between the different polymorphs of nano-size TiO2, with rutile being the most inflammogenic and amorphous being the most potent in regard to acute tissue damage.

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Rasic-Markovic, A., D. Hrncic, D. Krstic, M. Colovic, E. Djuric, B. Rankov-Petrovic, V. Susic, O. Stanojlovic und D. Djuric. „The effect of subchronic supplementation with folic acid and l-arginine on homocysteine-induced seizures“. Canadian Journal of Physiology and Pharmacology 94, Nr. 10 (Oktober 2016): 1083–89. http://dx.doi.org/10.1139/cjpp-2016-0076.

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The aim of the present study was to examine the effect of subchronic co-administration of folic acid (F) and l-arginine (A) on behavioural and electroencephalographic (EEG) characteristics of dl homocysteine thiolactone (H) induced seizures in adult rats. The activity of membrane ATPases in different brain regions were also investigated. Rats were treated with F, A, or vehicle for 15 days (regimen: F 5 mg/kg + A 500 mg/kg (F5A500); F 10 mg/kg + A 300 mg/kg (F10A300)). Seizures were elicited by convulsive dose of H (H, F5A500H, F10A300H) Subchronic supplementation with F and A did not affect seizure incidence, number of seizure episodes, and severity in F5A500H and F10A300H groups vs. H group. However, a tendency to increase latency and decrease the number of seizure episodes was noticed in the F10A300H group. EEG mean spectral power densities during ictal periods were significantly lower in F10A300H vs. H group. The activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost all examined structures in rats treated with F and A. We can conclude that subchronic supplementation with folic acid and l-arginine has an antiepileptic effect in dl homocysteine thiolactone induced epilepsy.

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Arjadi, Fitranto, Nur Signa Aini Gumilas, Ika Murti Harini, Vitasari Indriani und Lantip Rujito. „The Hepatotoxic and Nephrotoxic Effects of Purwoceng (Pimpinella pruatjan Molk.) Roots Ethanol Extract Administration in Subchronic Dose“. Molekul 16, Nr. 2 (20.07.2021): 163. http://dx.doi.org/10.20884/1.jm.2021.16.2.729.

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Purwoceng (Pimpinella pruatjan Molk) is an original Indonesian herb which is known to have an aphrodisiac effect. The active compounds in Purwoceng potentially have hepatotoxic and nephrotoxic effects.This study was aimed to analyze the effect of subchronic administration of Purwoceng roots ethanol extract to Wistar Strain of Rattus norvegicus rats. The method of this subchronic toxicity study was an experimental post test only with control group design. Forty male Rattus norvegicus were randomly divided into four groups and get 28-days treatment. Group A as control received aquadest and 1% CMC (carboxymethyl cellulose), group B, C, and D were given Purwoceng roots ethanol extract of 42, 84, and 168 mg/KgBW/day and 1% CMC. Parameters tested were the levels of urea, creatinine, SGPT (serum glutamic pyruvic transaminase), SGOT(serum oxaloacetic pyruvic transaminase), kidney and hepar histopatology.The results showed a statistically significant for the liver histopathological in group B, creatinine, urea, and kidney histopathology in group C. Our study concluded that subchronic administration of Purwoceng (Pimpinella pruatjan Molk) roots ethanol extract could induce hepatotoxicity at the 42 mg/KgBW/day dose level and nephrotoxicity at the 84 mg/KgBW/day dose level.

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Войценко К. І., Пальтов Є. В., Кривко Ю. Я. und Голейко М. В. „ДИНАМІКА МОРФОЛОГІЧНИХ ЗМІН СТРУКТУРНИХ КОМПОНЕНТІВ ХРЯЩОВОГО ПОКРИТТЯ КОЛІННОГО СУГЛОБА НА УЛЬТРАСТРУКТУРНОМУ РІВНІ НАПРИКІНЦІ ПЕРШОГО, ДРУГОГО ТА ТРЕТЬОГО ТИЖНІВ ОПІОЇДНОГО ВПЛИВУ“. Science Review, Nr. 1(18) (31.01.2019): 3–10. http://dx.doi.org/10.31435/rsglobal_sr/31012019/6334.

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The work presented below, aimed at studying the onset, development and manifestations of pathomorphic chondropathy in acute and subchronic experimental exposure of opioid analgesics. The objective was achieved by using microscopic visualization technique of cellular components of the articular cartilage. To obtain the microstructural materials we applied generally accepted, conventional methods.The results of the study in the future will allow to form a pathomorphological basis, which can be used for a comparative characterization of the structural components of the articular cartilage of the knee joint in the early and late stages (acute and subchronic) of experimental opioid exposure.

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Simic, Ivan, Violeta Iric-Cupic, Rada Vucic, Marina Petrovic, Violeta Mladenovic, Mirjana Veselinovic, Vladimir Ignjatovic und Jelena Vuckovic. „The subchronic effects of 3,4-methylendioxymethamphetamine on oxidative stress in rat brain“. Archives of Biological Sciences 66, Nr. 3 (2014): 1075–81. http://dx.doi.org/10.2298/abs1403075s.

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The aim of the present study was to evaluate the subchronic effects of 3,4-methylenedioxymethamphetamine on several oxidative stress markers: index of lipid peroxidation (ILP), superoxide dismutase (SOD) activity, superoxide radical (O2.-) levels, and reduced glutathione (GSH) levels in the frontal cortex, striatum and hippocampus of the rat. The study included 64 male Wistar rats (200-250g). The animals were treated per os with of 5, 10, or 20 mg/kg of 3,4-methylenedioxymethamphetamine (MDMA) every day for 15 days. The subchronic administration of MDMA resulted in an increase in ILP, SOD and O2.-, and a decrease in GSH, from which we conclude that oxidative stress was induced in rat brain.

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Bartoskova, Marta, Radka Dobsikova, Vlasta Stancova, Ondrej Pana, Dana Zivna, Lucie Plhalova, Jana Blahova und Petr Marsalek. „Norfloxacin—Toxicity for Zebrafish (Danio rerio) Focused on Oxidative Stress Parameters“. BioMed Research International 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/560235.

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The aim of the study was to investigate the effects of subchronic exposure of zebrafish (Danio rerio) to a fluoroquinolone norfloxacin, using selected oxidative stress parameters as a target. Toxicity tests were performed on zebrafish according to the OECD Guidelines number 203 and number 215. In the Subchronic Toxicity Test, a significant (P<0.01) increase in the activity of glutathione peroxidase, glutathione S-transferase, and catalase was found. In the test, norfloxacin did not affect lipid peroxidation and catalytic activity of glutathione reductase. From the results, we can conclude that norfloxacin has a negative impact on specific biochemical processes connected with the production of reactive oxygen species in fish tested.

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