Sinapic Acid Ameliorates the Progression of Streptozotocin (STZ)-Induced Diabetic Nephropathy in RatsviaNRF2/HO-1 Mediated Pathways

Diabetic neuropathy (DN) is a complicated inauspicious outcome of diabetes, like other abnormalities of diabetes the cause of DN is still vague and it may be the result of various pathological conditions leading up to end-stage renal failure. The present study examines the efficacy of sinapic acid (SA) in streptozotocin (STZ)-induced DN nephropathy and the linked pathway. Twenty-four rats were equally divided randomly into four categories: Normal control (NC), STZ, STZ + SA 20 mg/kg bw, and STZ + SA 40 mg/kg bw. After 8 weeks they were evaluated for ratio of renal index, the fasting blood glucose (FBG), blood urea nitrogen (BUN), 24 h urea protein, serum creatinine (SCr), reduced glutathione peroxidase (GPx), superoxide dismutase (SOD), lipid peroxidation (MDA), tumor necrosis factor alpha (TNF alpha), interleukin (IL)-6, as well as lipid profile total cholesterol (TC), total triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels. Additionally, histomorphology and ultrastructure of the kidneys were also assessed. Protein expression levels of transforming growth factor-beta 1 (TGF-beta 1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), I kappa B alpha protein (IkB alpha), anti-apoptotic protein BCl2, nuclear factor kappa B (NF-kB), and Bax were examined. We observed that SA 20 mg/kg bw and 40 mg/kg bw pretreatment significantly and dose-dependently upregulated the protein expression of HO-1, Nrf2, IKB alpha, and Bcl-2 but downregulated the protein expression of NF-kappa B, proposing that the nephroprotective mechanism of SA is due to its antioxidant and anti-inflammatory activity; SA prevents the release of cytokines and inflammatory markers (TNF alpha and IL-6), upregulates antioxidant defense enzymes, and reduces lipid peroxidation, as well as nitric oxide, and anti-apoptotic activity, which may be influenced by the regulation of TNF-alpha, IL-6, Bcl-2, NF-kB, and BaXviathe Nrf2/HO-1 pathway in STZ induced DN. Thus, our results suggest that SA ameliorates the development of STZ-induced DN in ratsviaNRF2/HO-1 mediated pathways. Further comprehensive studies are required for complete elucidation of the fundamental mechanisms.