Involvement of endocannabinoid system, inflammation and apoptosis in diabetes induced liver injury: role of 5-HT3 receptor antagonist

Background and Aim : Confident relationships between diabetes and liver damage have previously been established. This study was designed to evaluate hepatic inflammation, apoptosis and endocannabinoid system alterations in diabetes with or without tropisetron treatment.Methods : Rats were assigned to 5 equal groups; Control, Tropisetron, Diabetes, Tropisetron+Diabetes, and Glibenclamide+Diabetes (n=7 each group). Rats treated with tropisetron (3mg/kg) and glibenclamide (1mg/kg) for two weeks after type 1 diabetes induction.Results : Inflammatory cytokines Tumor necrosis factor alpha and Interleukin 6 (TNF- and IL-6), apoptotic cells and fatty acid amide hydrolase (FAAH) enzyme expression increased, while the expression of Cannabinoid Receptor 1 (CB1) reduced in the diabetic liver compared to control. Treatment with tropisetron reversed the inflammatory markers, apoptotic index and endocannabinoid system components. These effects were equipotent with glibenclamide, indicating that tropisetron can protect liver tissue against diabetic disturbances.Conclusion : These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent.

Keywords:

Diabetes , liver Injury , 5HT3 receptor , endocannabinoid system , inflammation , apoptosis , metabolic diseases