Role of Grape Seed Proanthocyanidins in the Suppression of High Calorie Diet-Induced Hepatic Injury and Apoptosis

Hepatocyte oxidative stress and apoptosis are considered to be the key components in the pathogenesis of nonalcoholic steatohepatitis. In this study we investigated the effect of grape seed proanthocyanidins (GSP) and metformin (MET), alone and in combination, on high fructose/fat diet (HFFD) induced steatohepatitis, with focus on oxidative stress and apoptosis markers. NASH was induced in male albino Wistar rats by feeding HFFD for 45 days. Either GSP (100 mg/kg b. w), MET (50 mg/kg b. w) or both were administered as therapeutic options. HFFD-feeding caused increase in lipid peroxides, protein carbonyls, proapoptotic proteins, (bax, caspases 3 and 9) and decline in anti-apoptotic protein (bcl2). Further, growth and DNA damage (GADD) 45, an NF-B regulated anti-apoptotic factor, was also reduced in HFFD-fed rats. These changes were reversed more effectively by GSP administration than by MET. Combined administration of GSP and MET showed synergistic effect in improving cell survival and hence could be considered for controlling HFFD-induced hepatocyte apoptosis.