Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats

• Published in: Biomedicine & pharmacotherapy 2016-08, Vol.82, p.685-692
• Main Authors: Hussein, Mohamed M.A, Mahfouz, Mohamed K
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Blood Glucose - metabolism; Body Weight - drug effects; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - physiopathology; Diabetic Nephropathies - blood; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - genetics; Diabetic Nephropathies - physiopathology; Diabetic nephropathy; Fibronectins - metabolism; FoxO1; Gene Expression Regulation - drug effects; Glycated Hemoglobin A - metabolism; Internal Medicine; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Male; Medical Education; Nerve Tissue Proteins - metabolism; NF-kappa B - metabolism; Oxidative Stress - drug effects; Rats, Wistar; Real-Time Polymerase Chain Reaction; Resveratrol; Rosuvastatin; Rosuvastatin Calcium - administration & dosage; Rosuvastatin Calcium - pharmacology; Rosuvastatin Calcium - therapeutic use; Sirt1; Sirtuin 1 - metabolism; Stilbenes - administration & dosage; Stilbenes - pharmacology; Stilbenes - therapeutic use; Transforming Growth Factor beta1 - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.06.004

Abstract The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5 mg/kg) alone or in combination with rosuvastatin (RSU) (10 mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats.