Protective effects of phloridzin against methotrexate-induced liver toxicity in rats
2017
Abstract Background Liver is the largest internal organ concerning with metabolism, hormonal balance and clarifying of the toxins. One of the main complications of methotrexate (MTX) therapy was the hepatic injury. Objective This study was conducted to elucidate the possible protective effects of phloridzin (PHL) against MTX-induced hepatotoxicity as compared to standard agent N-acetylcysteine (NAC). Materials and methods Rats were randomly divided into a normal control group, a respective group (PHL 40 mg/kg/day orally (p.o.) for 10 consecutive days), a hepatotoxicity control group (MTX 20 mg/kg, i.p., once), and three treated groups received NAC (150 mg/kg/day; a reference standard), PHL (40 mg/kg/day) and PHL (80 mg/kg/day) p.o. for 10 consecutive days, at the end of the day 3 of the experiment rats were administered MTX. Assessed biomarkers included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) as liver function parameters, serum tumor necrosis factor-α (TNF-α) and cyclooxygenase-II (COX-II), as inflammatory biomarkers, hepatic total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), glutathione reduced (GSH), nitrite (NO 2 − ), catalase (CAT), glutathione-S-transferase (GST) and superoxide dismutase (SOD) as oxidative stress biomarkers. Furthermore, hepatic caspase-3 expression was assessed. Biochemical and molecular estimations reinforced by histopathological findings. Results Rats pre-treated with PHL significantly reduced hepatic injury, evidenced by significant reductions in ALT, AST and LDH, TNF-α and COX-II levels, significant reductions in hepatic NO 2 − and TBARS levels, and significant elevations in hepatic TAC, GSH, GST, CAT and SOD levels. Additionally, downregulation of hepatic caspase-3 expression. Finally, histopathological results consistent with our previous findings. Conclusion PHL protects against hepatic injury in rats mainly through mitigation of oxidative stress, inflammation and apoptosis in hepatic tissues and may be promising to alleviate and early treatment of MTX-induced hepatoxicity in man.
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