Quercetin Mitigates Diabetic Nephropathy in Rats via Keap1/Nrf2/HO-1 Signaling Pathway

Abstract

A severe diabetic complication, diabetic nephropathy, progresses to terminal kidney disease. A chronic hyperglycemia-related excess of reactive oxygen species results in the advancement of diabetes complications. Through streptozotocin-induced diabetic nephropathy in rats, the present study investigated Quercetin’s renoprotective effect by upregulating nuclear factor-erythroid-related factor 2 (Nrf2) to cope with oxidative stress. During eight weeks study, daily food-water and weekly body weight were evaluated while biochemical, antioxidant parameters and genetic expression (Nrf2, Hemeoxygenease-1, Nuclear factor kappa B, Interlukin-6, and Caspase-3) were assessed at the end. The outcomes were interpreted using ANOVA, and the significance was determined using Dunnett’s test. Quercetin treatment for eight weeks significantly controlled hyperglycemia, dyslipidemia, and downregulated inflammatory activators NFκB, IL-6, and Caspase-3. The significant upregulation of Nrf2 gene expression reduced oxidative damage by promoting Antioxidant response elements and initiating downstream cascade (HO-1 and antioxidant enzymes). The results are supported by histopathology. Experimental evidence suggests that Quercetin can fight metabolic disorders and their related microvascular diseases by activating Nrf2.