Morin Hydrate Prevents Diabetic Nephropathy by Suppressing Oxidative Stress and 8-Hydroxydeoxyguanosine in Kidney Tissues

Abstract

Aims: The aim of this study was to investigate the protective effect of morin hydrate either individually or in combination with metformin against diabetic nephropathy by targeting oxidative stress and 8-hydroxydeoxyguanosine (8-OHdG) in the kidney tissue of rats with diabetic nephropathy. Methods: In this experimental study, diabetic nephropathy was induced in rats by injection of streptozotocin (STZ). The ability of morin hydrate to inhibit diabetic nephropathy was tested by screening lipid peroxidation (LPO), glutathione, glutathione peroxidase, superoxide dismutase, and catalase as parameters of oxidative stress; 8-OHdG as a marker of DNA damage and kidney injury molecule-1 (KIM-1) and aquaporin as indicators of kidney injury in renal tissues; and serum creatinine and blood urea nitrogen as markers of renal function using biochemical, immunohistochemical, and immunofluorescence methods. Results: Significant increases (p<0.0001) in LPO, 8-OHdG, KIM-1, and aquaporin levels and significant decreases (p<0.0001) in glutathione, glutathione peroxidase, superoxide dismutase, and catalase levels were observed after STZ administration, indicating the development and progression of diabetic nephropathy. Treatment with morin hydrate, especially in combination with metformin, suppressed the oxidant levels and improved the antioxidant system and the histopathological integrity of the kidney, which was positively reflected in the levels of KIM-1, aquaporin, and kidney function parameters. Conclusion: Morin hydrate prevents diabetic nephropathy resulting from diabetes mellitus by suppressing oxidative stress and 8-OHdG levels in kidney tissues. Therefore, this bioflavonoid represents a promising candidate for patients with diabetic nephropathy. Moreover, the combination therapy of morin hydrate and metformin achieved better effectiveness than the single treatment, which emphasizes an important synergistic role of morin hydrate and metformin in managing patients with diabetic nephropathy.