Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats

This study explored the hepatoprotective mechanisms of ALA against MTX-induced hepatic injury in rats. Hepatic injury was induced in MTX group by 20 mg/kg body weight ip. injection of MTX. ALA group was pretreated with ALA 60 mmol/kg body weight ip. for five days followed by a single dose of MTX in the sixth day. Blood samples and liver tissues were then obtained to assess several biochemical parameters as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), reduced glutathione (GSH), total antioxidant capacity (TAC) and lipid peroxidation. Nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway was studied by determining the extent of mRNA Nrf2 expression and the level of HO-1. Hepatic stellate cells (HSCs) activation was evaluated by estimating the expression of α-smooth muscle actin (α-SMA) and hydroxyproline content. Also, tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and caspase-3 were assessed by ELISA in addition to histopathological examination of liver samples. Results showed that ALA pretreatment improved liver function since serum ALT, AST and ALP levels were reduced. Additionally, ALA restored GSH and TAC levels when compared to MTX group and decreased lipid peroxidation. ALA exerted its antioxidant effect via Nrf2/HO-1 pathway as well as it showed anti-inflammatory and antiapoptotic effects by reducing TNF-α, iNOS, COX-2 and caspase-3 le...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research