Effects of probucol on hepatic tumor necrosis factor-α, interleukin-6 and adiponectin receptor-2 expression in diabetic rats

Background and Aims:  Probucol is a lipid-lowering agent with anti-oxidant effects. Oxidative stress and inflammation are important in the pathophysiology of insulin resistance. We aimed to evaluate the effects of probucol on liver histological changes, serum and hepatic levels of adipokines in rats with high fat-induced type 2 diabetes (T2D).
Methods:  Thirty-six rats were divided into a normal control group, a high fat-induced T2D group and a probucol treatment group. After six weeks of treatment with probucol, we evaluated liver histological changes and measured homeostasis model assessment index (HOMA-IR), serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin and hepatic TNF-α, IL-6 and adiponectin receptor-2 (adipoR2) mRNA.
Results:  The degree of hepatic steatosis and inflammation, HOMA-IR, serum ALT, TNF-α and IL-6 concentrations, and hepatic TNF-α and IL-6 mRNA expression in diabetic rats were significantly higher compared with normal controls. Serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression in diabetic rats were significantly lower compared with normal controls. Probucol significantly reduced the degree of hepatic steatosis, HOMA-IR, serum ALT, TNF-α and IL-6 concentrations, and hepatic TNF-α and IL-6 mRNA expression. Probucol significantly raised serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression.
Conclusions:  In rats with high fat-induced T2D, treatment with probucol improved insulin sensitivity, hepatic steatosis by raising circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokines in the circulation and liver.