Mechanistic Study of Potential Hepatoprotective Effect of Liraglutide in an Experimental Model of Liver Toxicity

Abstract

The current work was designed to investigate the potential hepatoprotective effect of liraglutide in methotrexate-induced liver injury model as well as its underlying molecular mechanisms by studying its effects on some key events such as oxidative stress, inflammation and apoptosis signaling pathway. To fulfill these goals, this study was divided into two parts: I- Dose screening for the optimum hepatoprotective dose of liraglutide After acclimatization for 2 weeks, 48 rats were randomly divided into six groups of eight rats each and treated for 10 consecutive days as follows: Group 1: served as a negative control, receiving saline only during the entire experimental period. Group 2: given a single intraperitoneal injection of methotrexate at a dose of 20 mg/kg BW on the eighth day. Group 3, 4, and 5: received liraglutide at a dose of 0.3, 0.6 and 1.2 mg/kg respectively i.p twice daily and on the eighth day was given single i.p MTX injection at a dose of 20 mg/kg. The dose range of liraglutide is selected based on previous reports The assessed parameters for phase I to select the optimum liraglutide dose were: 1. Assessment of liver enzymes: Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT) 2. Histopathological examination H & E II- Studying the hepatoprotective mechanism of liraglutide against MTX induced liver injury Based on serum ALT & AST and histopathological examination results, liraglutide 1.2 mg/kg dose was selected to be the optimum hepatoprotective dose and used for assessment of oxidative stress and inflammatory markers and studying the signaling hepato-protection pathway.