Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) & TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.