Renal protection by acacetin in streptozotocin-induced diabetic nephropathy via TLR4/NF-κB pathway modulation in rats

Background. Diabetic nephropathy (DN), the most severe microvascular consequence of diabetes mellitus (DM), is the precursor to end-stage renal disease (ESRD). The development of problems linked to DN involves both oxidative damage and inflammation. Natural flavone acacetin (AC) has anti-inflammatory, antioxidant and anti-cancer properties. However, the effect of AC on DN is not clear. Objectives. To investigate potential nephroprotective effects of AC caused by reducing inflammation and oxidative stress via the TLR4/NF-kappa B pathway in rats with streptozotocin (STZ)-induced DN. Materials and methods. In this study, we investigated the nephroprotective effect of AC compared to that of a positive control therapy of irbesartan (IRB) in DN induced with STZ. In this model, rats were given an intraperitoneal injection of STZ (180 mg/kg body weight (BW)), along with daily doses of AC (10 mg/kg BW) or IRB (180 mg/kg BW) to induce DN. Histopathology, albumin, blood glucose (Bg), BW, oxidative stress indicators, and western blot of inflammatory signaling pathways in the kidney were examined. Results. Reduction of blood glucose, proteinuria, serum malondialdehyde (MDA), serum creatinine, and blood urea nitrogen (BUN), as well as the inhibition of toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1) and nuclear factor kappa B (NF-kappa B) protein expression were observed. These data demonstrated that AC could improve BW, antioxidant enzyme and renal histopathology in rats with STZ-induced DN. Conclusions. Results from the rat model highlight how AC-suppressed inflammation and oxidative stress can attenuate STZ-induced DN by downregulating the TLR4/NF-kappa B pathway in rats.