title: Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats.
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) (5mg/kg) alone or in combination with rosuvastatin (RSU) (10mg/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.
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt. Electronic address: hamza_vet@yahoo.com.
authors.forename: Mohamed M A
authors.initials: MM
authors.lastname: Hussein
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, Egypt.
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Mahfouz
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D005353:Fibronectins; D006442:Glycated Hemoglobin; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D000077185:Resveratrol; D000068718:Rosuvastatin Calcium; D056564:Sirtuin 1; D013267:Stilbenes; D053773:Transforming Growth Factor beta1; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
keywords: Diabetic nephropathy; FoxO1; Resveratrol; Rosuvastatin; Sirt1