Quercetin ameliorates diabetic nephropathy in rats via modulation of renal NA⁺, K⁺-atpase expression and oxidative stress

Diabetic Nephropathy (DN) is one of most prevalent complications of Diabetes Mellitus (DM), therefore prevention of its development is a important field for researches. Quercetin is a plant flavenoid with hypoglycemic and antioxidant properties that is claimed to have a reno-protective effect in diabetes. This study was designed to investigate the reno-preventive role of Quercetin treatment in terms of biochemical and pathological changes in diabetic rats and to determine whether the effect is mediated through modulation of oxidative stress and Na⁺, K⁺ ATPase expression and activity. Sixty male Sprague-Dawley rats were distributed equally among 6 groups: (i) Control group (C), (ii) Quercetin treated Control group (CQ), (iii) Diabetic group (D), (iv) Diabetic Insulin treated group (DI), (v) Diabetic Quercetin treated group (DQ) and (vi) Diabetic Insulin and Quercetin treated group (DIQ). Systolic blood pressure was measured at the end of the experiments (8 weeks). Retro-orbital blood samples were used to determine the serum levels of glucose, HbA1c, urea, creatinine, Na⁺ and K⁺. Renal homogenate levels of Na⁺, K⁺ATPase activity, Malondialdehyde (MDA0, Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) were measured. Semiquantitative reverse transcriptase-PCR Na⁺, K⁺ATPase expression assays and kidney histopathological examination were conducted. Treatment with either insulin or Quercetin alone resulted in partial reversal of the biochemical and histopathological signs of nephropathy in diabetic rats. This was associated with partial but significant amelioration of indicators of oxidative stress and Na⁺, K⁺ATPase gene expression and activity. However only combined treatment by both insulin and Quercetin significantly improved all of the aforementioned parameters up to the control levels. These results suggested that combined therapy with insulin and Quercetin might be a useful preventive tool against development of DN.