title: Beneficial effects of Chrysin against Methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis.
abstract: Methotrexate (MTX), a folic acid antagonist, an effective chemotherapeutic agent is used in the treatment of a wide range of tumors and autoimmune diseases. Moreover, hepatotoxicity limits its clinical use. Several studies have already confirmed that the oxidative stress plays a major role in the pathogenesis of MTX-induced damage in the various organs especially in liver. The aim of this study was to determine the protective effect of Chrysin against MTX-induced hepatic oxidative stress and apoptosis in rats. In the present study, efficacy of Chrysin was investigated against hepatotoxicity caused by MTX in terms of biochemical investigations of antioxidant enzymes, apoptosis, and histopathological alteration in rat liver. In the MTX-treated group there was a significant increase in alanine transaminase, aspartate aminotransferase, lactate dehydrogenase activity and malondialdehyde content as well as decreased glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase activities and reduced glutathione content were also observed compared to the control group as a marker of oxidative stress. Histopathological alterations and apoptosis through the immunopositive staining of p53, cleaved caspases-3 and Bcl-2-associated X protein in rat liver were observed. Pretreatment of Chrysin at both doses prevents the hepatotoxicity by ameliorating oxidative stress, histopathological alterations, and apoptosis and thus our results suggest that Chrysin has a protective effect against hepatotoxicity induced by MTX and it may, therefore, improve the therapeutic index of MTX if co-administration is done.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India.
authors.forename: Nemat
authors.initials: N
authors.lastname: Ali
authors.forename: Summya
authors.initials: S
authors.lastname: Rashid
authors.forename: Sana
authors.initials: S
authors.lastname: Nafees
authors.forename: Syed Kazim
authors.initials: SK
authors.lastname: Hasan
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D005419:Flavonoids; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C043561:chrysin; D008315:Malondialdehyde; D053148:Caspase 3; D005978:Glutathione; D008727:Methotrexate