Febuxostat offers protection against diabetic nephropathy possibly through modulation of hmgb1/nf-eb signaling in rats

Diabetic nephropathy (DN), an early-stage renal failure, is a common serious complication of uncontrolled diabetes mellitus (DM). Untreated DN may progress to the fatal end-stage renal disease. Hyperuricemia, oxidative stress and inflammatory signaling are believed to mediate DN progression. This study investigated the possible protective effect of xanthine oxidase inhibitor febuxostat was examined in a rat model of DN. Briefly, animals were allocated into four groups, the control group receiving vehicle and standard diet, a DN group receiving streptozotocin (STZ; 50 mg/kg, i.p, single dose) with a high fat diet (HFD), and two treatment groups receiving febuxostat (5 and 10 mg/kg/day, p.o., 14 days) together with STZ and HFD. The DN rats showed significant increasein microalbuminuria and creatinine clearance without significant elevation of serum creatinine level, an indication ofearly-stage renal injury. Febuxostat showed significant dose-dependent improvements of oxidative and inflammatory biomarkers in the renal tissue, including malondialdehyde (MDA), glutathione (GSH), nitric oxide end products (NOx) and interestingly high-mobility group box-1 (HMGB1) and nuclear factor-kappa B (NF-eB) together with serum uric acid. The observation of this study revealed that febuxostat could be a promising protective agent against DN progression through amelioration of hyperuricemia, modulation of HMGB1/NF-eB signaling and subsequent antioxidant and anti-inflammatory capability.