Treatment with geraniol ameliorates methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in rats.

Abstract

Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. The aim of this work was to investigate whether treatment with geraniol (a monoterpene) attenuated NASH induced by methionine-choline-deficient (MCD) diet in rats. Rats were fed with MCD diet to induce NASH and treated with geraniol (200 mg/kg/day) for 10 weeks. Treatment with geraniol reduced histological scores, fibrosis, and apoptosis in livers, lowered activities of alanine aminotransferase and aspartate aminotransferase in serum, and attenuated hepatic fat accumulation in rats fed with MCD diet. Treatment with geraniol preserved hepatic mitochondrial function, evidenced by reduced mitochondrial reactive oxygen species formation, enhanced adenosine triphosphate formation and membrane integrity, restored mitochondrial electron transport chain enzyme activity, and increased mitochondrial DNA content in rats fed with MCD diet. Treatment with geraniol reduced uncoupling protein 2 protein expression, and enhanced protein expression of prohibitin, mRNA expression of peroxisome proliferator-activated receptor α, and activity of mitochondrial carnitine palmitoyl transferase-I in livers of rats fed with MCD diet. Treatment with geraniol abated oxidative stress, evidenced by reduced malondialdehyde and 3-nitrotyrosine formation, enhanced activity of glutathione S-epoxide transferase, and down-regulated expression of inducible nitric oxide synthase and cytochrome P450 2E1 in livers of rats fed with MCD diet. Treatment with geraniol reduced myeloperoxidase activity and protein expression of tumor necrosis factor alpha and IL-6 in livers of rats fed with MCD diet. Treatment with geraniol attenuated MCD-induced NASH in rats.