Macrophage Inhibitory Factor in Myocardial Oxidative Stress and Inflammation During Thioacetamide-Induced Liver Fibrosis: Modulation by Betaine

Abstract

Chronic liver disease is closely associated with impaired cardiovascular function. Cardiac dysfunction is caused in part by oxidative stress and increased levels of proinflammatory and profibrogenic mediators in myocardial tissue. The present study aims to investigate the role of betaine in the modulation of MIF-mediated oxidative stress, inflammation, and fibrogenesis in heart during TAA-induced liver fibrosis in mice. The experiment is performed on wild-type and knockout MIF−/− C57BL/6 mice (MIF−/− group). They are randomly divided into groups: Control; Bet-group, received betaine (2% wt/v dissolved in drinking water); MIF−/− mice group; MIF−/−+Bet; TAA-group, treated with TAA (200 mg/kg b.w.), intraperitoneally, 3×/week/8 weeks); TAA+Bet; MIF−/−+TAA, and MIF−/−+TAA+Bet group. After eight weeks of treatment, animals are sacrificed and heart samples are taken to determine oxidative stress parameters, proinflammatory cytokines, profibrogenic factors, and histopathology of myocardial tissue. Our results suggest that MIF contributes significantly to lipid peroxidation of cardiomyocytes, as well as oxidative and nitrosative stress in myocardial tissue in mice with TAA-induced liver fibrosis compared to the control group. In addition, MIF was important for myocardial expression of the proinflammatory cytokines IL-6 and TNF as well as the profibrogenic mediators TGF-β1 and PDGF-BB in TAA-treated mice. Notably, betaine attenuated MIF effects in myocardial tissue reducing levels of MDA, AOPP, TNF, TGF-β1, PDGF-BB and increasing SOD and catalase activity in the coexistence of liver fibrosis. These results emphasize the potential of betaine as a therapeutic agent in mitigating MIF effects and demonstrate the need for further research into its optimal dosage and efficacy in preventing or slowing down cardiac dysfunction in patients with liver cirrhosis