PPAR-α agonist fenofibrate potentiates antioxidative elements and improves oxidative stress of hepatic cells in streptozotocin-induced diabetic animals

Oxidative stress induced by hyperglycemia has a crucial role in hepatocellular disorders. The aim of this study was to evaluate whether fenofibrate potentiates the anti-oxidant defense system of hepatocytes and thereby prevents oxidative stress. Male Wistar rats were assigned to four groups: normal control (C), normal-treated (CF), diabetic (D), and diabetic-treated (DF) (n = 6 per group). Hyperglycemia was induced with streptozotocin (single dose of 45 mg/kg into the tail vein). Treated groups received fenofibrate for 8 weeks by intragastric gavage (80 mg/kg/day). At study completion (day 56), the rats were sacrificed and liver tissue harvested. Catalase (CAT) and superoxide dismutase (SOD) enzymes activities, malondialdehyde (MDA), nitrate, and glutathione (GLT) contents were evaluated in all experimental groups. Obtained data were analyzed via two-way ANOVA, p < 0.05 taken as significant. Hyperglycemia markedly decreased SOD and CAT enzyme activities; furthermore, oxidative stress was induced via MDA content enhancement. Fenofibrate increased both SOD and CAT enzyme activities and decreased the nitrate content and MDA production in hepatic cells, thus improving oxidative stress. Our data suggest that uncontrolled hyperglycemia overwhelms the anti-oxidant defense systems of hepatic cells and oxidative damage ensues. The PPAR-α agonist Fenofibrate prevents oxidative damage in hepatocytes by potentiating the anti-oxidant defense system and can therefore improve the redox state in hepatocellular tissue.