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Background: Due to the fact that methotrexate is widely used both as an immunosuppressive drug and as a chemotherapy agent, many studies are needed to reduce the side effects of this drug on non-target organs., Purpose: This study was designed to investigate the effects of epicatechin (Epi) on MTX (methotrexate)-induced hepatotoxicity in mice., Research Design: After 1 week for adaptation, we randomly divided 42 male Naval Medical Research Institute mice into six groups: (I) control; (II) Epi (100 mg/kg, po); (III) MTX (20 mg/kg, i.p.) on the fifth day; and (IV, V, and VI) Epi (25, 50, and 100 mg/kg, po) + MTX (20 mg/kg, i.p.) on the fifth day. At day 10, the mice were sacrificed and serum factors, oxidative stress markers, and inflammatory cytokines were measured., Results: MTX increased activity level of serum enzymes (alanine aminotransferase and aspartate aminotransferase), lipid peroxidation marker (malondialdehyde), and inflammatory factors including interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide. Furthermore, MTX decreased glutathione level and activity level of catalase, superoxide dismutase, and glutathione peroxidase. Epi was able to reduce the destructive effects of oxidative/antioxidant system imbalance and inflammatory reactions and also histopathological damage in MTX intoxicated mice. Epi pretreatment reduced liver dysfunction by improving the antioxidant defense system, anti-inflammatory effects, and alleviation of histopathological damage in MTX hepatotoxicity., Conclusions: Accordingly, Epi can be used as a therapeutic agent in hepatotoxicity associated with MTX chemotherapy.

Introduction: In multiple studies, involvement of oxidative stress in the pathogenesis of methotrexate (MTX)-mediated liver damage has been confirmed. Use of many drugs has been examined experimentally in order to prevent or diminish oxidative stress. However, no study has yet examined the effects of ferulic acid (FA) on MTX-induced liver damage. This study aimed at evaluating the effects of FA on protection against liver damage induced by MTX in mice., Materials and Methods: In this the mice were divided into five groups in a random manner: I) control; II) MTX (20 mg/kg); III and IV) FA (50 and 100 mg/kg) + MTX; and V) FA (100 mg/kg), and we measured serum factors, oxidative stress and inflammatory factors., Results: In the MTX group, accumulation of inflammatory cells, accumulation of red blood cell (RBC), and nuclear pyknosis (NP) were detected in the liver. In line with the histological data, the levels of nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α increased (TNF-α), whereas the reduced glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) content reduced in the MTX group. However, FA ameliorated these hazardous effects in the antioxidant and anti-inflammatory systems in MTX-treated groups., Conclusion: Based on our findings, oxidative stress impairment and MTX-induced liver damage were ameliorated following FA pretreatment at both histological and biochemical levels. Therefore, FA can be effectively used in abrogation of MTX-induced toxicity., Competing Interests: All authors declare no conflict of interest related to the present work., (© 2020 Roghani et al.)

Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In the present study, hepatoprotective effect of Cassia fistula fruit extract was investigated in mice. Animals were divided into six groups receiving normal saline (1), bromobenzene (460 mg/kg) alone (2) and together with increasing doses (200, 400, 600, 800 mg/kg) of a crude hydro-alcoholic extract of Cassia fistula fruit (3-6, respectively). All administrations were carried out orally, daily, for 10 days. On the 11th day, animals were sacrificed. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT) were determined; serum levels of direct and total bilirubin were measured; furthermore, livers were prepared for histological examination. Our results showed that bromobenzene treatment alone elicited a significant increase in activities of AST, ALT, ALP (but not γGT), and it significantly elevated the levels of direct and total bilirubin. Co-treatment with Cassia fistula fruit extract, however, significantly and dose-dependently decreased the above-mentioned enzyme activities (with exception of γGT) and bilirubin levels, producing a recovery to the naive state. The protective effect of Cassia fistula fruit extract against liver injury evoked by bromobenzene was confirmed by histological examination as well. In conclusion, the Cassia fistula fruit extract has significant hepatoprotective effect in our murine model.

Objective: The aim and purpose of this study was to find out the protective effect of garlic oil in liver toxicity induced by acetaminophen overdose and the comparison of its effect with N-acetylcysteine in albino male mice (18-22 g)., Methods: This study was undertaken during the period from January 1999 through to August 2000, at the School of Pharmacy, Ahwaz University of Medical Sciences, Ahwaz, Iran. All animals were fasted over night and were divided into 8 groups. Each group consisted of 10 mice. Garlic oil was administered intraperitoneally in doses of 100mg/kg, 200mg/kg and 500 mg/kg. Immediately after this, a toxic dose of acetaminophen (500 mg/kg orally) was administered followed by another administration one hour later (500 mg/kg orally). Twenty-four hours after the last administration, blood was withdrawn from the jugular vein of the mice and serum enzyme activities were measured and compared with the control groups. The liver samples were studied for the histopathological examination., Results: The results in group which received 200mg/kg of garlic oil showed good protection activity as compared with the positive control group. The histopathological observations also showed that the area of liver damage was reduced significantly as compared with the positive control group. The severity of injury was variable among the animals and there was less evidence of necrosis in this group. Some protection was observed in other doses of garlic oil but these were not much significant. The results obtained one hour after acetaminophen intoxication (post treatment) showed a less protective effect as compared with the group which received garlic oil simultaneously after acetaminophen intoxication., Conclusion: Garlic oil, as similar to N-acetylcysteine, can eliminate electrophilic intermediates and free radicals through conjugation and reduction reactions. Therefore it protects the liver from toxic doses of acetaminophen. In the present study we also observed the protection by the garlic oil. The clearance of the toxic metabolites of the acetaminophen from the liver occurs much faster in immediate treatment with garlic oil (200mg/kg).