Downregulation of apoptosis and modulation of TGF-β1 by sodium selenate prevents streptozotocin-induced diabetic rat renal impairment.
To investigate whether sodium selenate treatment would impact on the onset of diabetic nephropathy, we examined blood glucose, serum biochemical components, and interrelationship between oxidative stress, TGF-β1, and apoptosis in streptozotocin (STZ) induced diabetic rats. Sixty male Wistar rats were divided into six groups. Group I (n = 10), normal control; Group II (n = 10), diabetic control; Group III (n = 10), sodium selenate (16 μmoles/kg) + diabetic; Group IV (n = 10), sodium selenate (32 μmoles/kg) + diabetic; Group V (n = 10), sodium selenate (16 μmoles/kg) control; and Group VI (n = 10), sodium selenate (32 μmoles/kg) control. Sodium selenate was administered via orogastric route for 10 weeks. In the diabetic group, diabetes was induced by single intraperitoneal injection of STZ (50 mg/kg). The levels of blood glucose were estimated and total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, creatinine, urea, and albumin were detected in serum. Antioxidant status was examined by measuring the superoxide dismutase (SOD), catalase, glutathione, and lipid peroxidation in kidney tissues. Histopathological studies were performed in the kidney tissue sections. The expression of TGF-β1 was estimated by the immunohistochemical analysis in kidneys. Apoptotic study in kidney was performed using the TdT-mediated dUTP nick end labeling technique. It was observed that blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin were significantly higher in diabetic control groups. Diabetic + sodium selenate (16 and 32 μmoles/kg) significantly reduced blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin levels. Selenium-treated groups significantly increased antioxidant enzyme activities (SOD, catalase, and glutathione) in kidneys of diabetic rats. All enzyme activities of selenium control groups did not differ compared with the normal control. Sodium selenate reduces significantly lipid peroxidation in diabetic rats. Cellular architecture of the diabetic rats was altered whereas sodium selenate administration rectifies the degenerative changes of the kidney. Profound immunopositivity of TGF-β1 was observed in the glomerular and tubulointerstitial cells of diabetic rat kidney. Immunopositivity of TGF-β1 was significantly reduced in both low and high dose of sodium-selenate-treated rats (P < 0.05, P < 0.01). High numbers of apoptotic cells were observed in diabetic rats whereas sodium selenate in both doses significantly reduces the incidence of apoptosis (P < 0.05, P < 0.01). We conclude herein that sodium selenate has the potential to play a significant role in limiting the renal impairment by altering the apoptosis and TGF-β1 in experimental diabetic rats.
Roy
Souvik
S
Department of Pharmacology, St. Peter's Institute of Pharmaceutical Sciences, Hanmakonda, Warangal, Andhra Pradesh 506001, India. souvikroy35@gmail.com
Dontamalla
Sudheer Kumar
SK
Mondru
Anil Kumar
AK
Sannigrahi
Santanu
S
Veerareddy
Prabhakar Reddy
PR
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D064586:Selenic Acid; D018036:Selenium Compounds / Q000627:therapeutic use*; D013311:Streptozocin / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000975:Antioxidants; D018036:Selenium Compounds; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D064586:Selenic Acid