Prophylactic Resveratrol and Telmisartan Combination Ameliorates Experimentally-Induced Diabetic Nephropathy in Rats, Focus on the Pro-Sclerotic Cytokine, Transforming Growth Factor-ß1 (TGF-ß1)
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Prophylactic Resveratrol and Telmisartan Combination Ameliorates Experimentally-Induced Diabetic Nephropathy in Rats, Focus on the Pro-Sclerotic Cytokine, Transforming Growth Factor-ß1 (TGF-ß1),OMAIMA M. ABD ALLAH and FOUAD EL-DEBAKEY
Abstract
Objectives: Prevention or retardation of diabetic nephr-opathy (DN) has become a major goal in biomedical research. Local renal renin-angiotensin system (RAS) activation and increased oxidative stress have been implicated in the patho-genesis of diabetic nephropathy, this study tested the prophy-lactic effect of resveratrol (Res), as a natural antioxidant, or telmisartan (Tel), an angiotensin II receptor antagonist, and their combination on the development and progression of diabetic nephropathy (DN) in experimentally-induced diabetes in albino rats.
Material and Methods: 48 male albino rats equally divided into 6 groups; 2 negative control groups and 4 diabetic groups. Diabetes was induced by single dose of streptozotocin (50 mg/kg i.p.). Diabetic rats received; no prophylaxis (DN group), prophylaxis with Tel or Res alone or their combination. At the end of 12 weeks, systolic blood pressure and body weight were determined. Blood glucose, serum urea and creatinine were estimated. Also, 24-h urinary proteins and creatinine clearance (Ccr) were determined. Fresh urine samples were collected for estimation of urinary Transforming Growth Factor-ß1 (TGF-ß1). Cortical total RNA was extracted and the mRNA expression of TGF-ß1 was determined by a “two-step” RT-PCR.
Results: Prophylaxis therapy either by Tel or Res alone induced significant attenuation of DN, the combined therapy was additive, with significant reduction in blood pressure and proteinuria. Single-line prophylaxis therapy reduced urinary TGF-ß1 and renal tissue TGF-ß1 mRNA expression levels significantly. However, combination therapy with Tel+Res induced superior effect compared to each used alone.
Conclusion: Resveratrol showed a renoprotective effect manifested as significant reduction of TGF-ß1 with its fibro-genic effect and being an herbal drug could be advised for early-stage diabetics without evident manifestations of neph-ropathy as a prophylactic therapy and due to the additive beneficial effects of its combination with telmisartan, both could be used as combination therapy for patients developed manifestations.