The role of cannabinoid receptor 1 in the development of oxidative/nitrosative stress in mice with non-alcoholic fatty liver disease

Abstract

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is hepatic manifestation of metabolic syndrome. It represents a spectrum of diseases ranging from steatosis, non-alcoholic steatohepatitis (NASH), that may progress to fibrosis, cirrhosis and eventually hepatocellular carcinoma. Aim: The aim of the study was to investigate the influence of CB 1 cannabinoid receptor blockade on the intensity of oxidative/nitrosative stress in mice liver with NAFLD. Therefore, we used rimonabant, selective CB 1 antagonist. Material and Methods: Male mice C57BL/6 (n = 28) were divided into following groups: 1) Control group-fed with control chow diet 20 weeks (C group; n = 7), 2) Group fed with high saturated fat diet 20 weeks (HF group; n = 7), 3) Group fed with standard chow diet and treated with rimonabant after 18 weeks (R group; n = 7), 4) Group fed with high saturated fat diet and treated with rimonabant after 18 weeks (HFR group; n = 7). The activity of liver transaminases was measured in serum. The concentrations of malondialdehyde (MDA), nitrites and nitrates (NO x), and the activity of superoxide dismutase (SOD), copper/zinc superoxide dismutase (Cu/ZnSOD) and manganese superoxide dismutase (MnSOD) were measured in the liver. Results: Rimonabant induced decrease in transaminase activity in R group compared to control, as well as in HFR group compared to HF group (p < 0.01, respectively). Concentrations of MDA and NO x were lower in HFR compared to HF group (p < 0.01). We found decrease in SOD, Cu/ZnSOD and MnSOD activities in HFR group compared to HF group (p < 0.01). Conclusion: According to the results of this study, it can be concluded that blockade of CB 1 receptors causes useful effects in the treatment of NAFLD. Rimonabant reduced hepatocellular injury, which was proved by decreased transaminase activities. The reduction of oxidative/ nitrosative stress and lipid peroxidation may also contribute to the protective effects of rimonabant, which has been shown as decrease in MDA and NO x concentration.