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-κB pathway in rats with streptozotocin (STZ)-induced DN. MATERIAL 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-κB) 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-κB pathway in rats.