Betaine treatment protects liver through regulating mitochondrial function and counteracting oxidative stress in acute and chronic animal models of hepatic injury.

Betaine is a derivative of the amino acid glycine widely investigated for its hepatoprotective properties against alcoholism. The protective properties of betaine in different other experimental models also have been documented. On the other hand, the exact cellular mechanism of cytoprotection provided by betaine is obscure. The current study was designed to evaluate the hepatoprotective effects of betaine and its potential mechanisms of hepatoprotection in two animal models of acute and chronic liver injury. Bile duct ligation (BDL) was used as a model of chronic liver injury and thioacetamide (TAA)-induced hepatotoxicity was applied as the acute liver injury model. Severe increase in serum markers of liver tissue damage along with significant liver tissue histopathological changes were evident in both acute and chronic models of hepatic injury. It was also found that tissue markers of oxidative stress were significantly increased in BDL and TAA-treated animals. Moreover, liver mitochondrial indices of functionality were deteriorated in both investigated models. Betaine supplementation (10 and 50 mg/kg, i.p) ameliorated hepatic injury as judged by decreased liver tissue histopathological alterations, a significant decrease in tissue markers of oxidative stress, and mitigation of serum biomarkers of hepatotoxicity. On the other hand, betaine (10 and 50 mg/kg, i.p) protected hepatocytes mitochondria in both chronic and acute models of hepatotoxicity. These data indicate that the antioxidative and mitochondria regulating properties of betaine could play a primary role in its mechanisms of hepatoprotection.