Effects Of Probucol And Fosinopril On Liver Steatosis In Rats With Type 2Diabetes

Aims To detect the effects and the potential mechanisms of probucol and fosinopril on liver steatosis in rats with type 2 diabetesMethods Male Wistar rats, weighing 140～160 g, were fed with normal chow for one week, and then randomly divided into two groups: the control group (C, twelve rats) was fed with normal chow, while another group (thirty-six rats) was fed with high-fat diet. Four weeks later, the rats in the control group were injected intraperitoneally with saline, while the rats in high-fat diet group were injected with streptozotocin (STZ) (35 mg/kg) to induce type 2 diabetes model (fasting serum glucose≥7.8 mmol/l), then they were randomly divided into three groups (twelve rats in each group). Rats in the Probucol group (P group) were fed with high-fat diet and probucol (500 mg/(kg*d), lavage); Rats in the Fosinopril group (F group)were fed with high-fat diet and fosinopril (5.0 mg/(kg*d), lavage); Rats in high-fat diet group (HD group) were fed with high-fat diet and saline (2 ml/(one*d), lavage). Six weeks later, we measured the ratio of liver weight to body weight, serum ALT, AST, TG, TCHO, MDA and SOD activity, ISI, IRI, serum adiponectin level, expression of adiponectin receptor 2 (adipoR2) mRNA in liver tissue and histological scoring for non-alcoholic fatty liver disease (NAFLD) in all experimental groups.Results TCHO, ALT and IRI were significantly reduced in Probucol group compared with HD group (p < 0.05, p < 0.05, p < 0.05), while SOD activity and ISI were elevated (p < 0.05, p < 0.001). Serum ALT and IRI were significantly reduced in Fosinopril group compared with HD group (p < 0.01, p < 0.05), whereas SOD activity and ISI were elevated (p < 0.05, p < 0.001), and had no effect on TG and TCHO. The ratio of Liver weight to Body weight was reduced in Probucol group (p < 0.05), but aggravated in Fosinopril group (p < 0.001) compared with HD group. The serum adiponectin concentrations and hepatic adipoR2 mRNA expression significantly raised both in Probucol group and Fosinopril group (p < 0.05 respectively).Liver lobular inflammation and steatosis were improved both in Probucol and Fosinopril group.Conclusion In rats with high fat-induced T2D, treatment with probucol can improve liver steatosis and inflammation, decrease TCHO level and oxidative stress, enhance local reaction of adiponectin in liver and improve insulin resistance. Treatment with fosinopril also can improve liver steatosis and inflammation, decrease oxidative stress and enhance local reaction of adiponectin in liver and improve insulin resistance, but have no effect on TCHO. Hepatomegaly was reduced by probucol treatment, but aggravated by fosinopril treatment. The adverse effect of fosinopril on aggravating hepatomegaly should be furtherly investigated.