الفهرس 
Title : Comparative study of the protective effects of certain vasodilators on streptozotocin-induced diabetic nephropathy in rats
AbstractOnly 14 pages are availabe for public view
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Abstract
Diabetic nephropathy (DN) is a chronic complication which is evoked by elevated glucose levels in diabetes mellitus (DM) by different pathological pathways. Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of DN. Gliclazide (10 mg/kg/day), vinpocetine (30 mg/kg/day) and geraniol (200 mg/kg/day) were administered daily to diabetic rats for 6 weeks starting on the 3rd day post diabetes induction by streptozotocin (STZ) (45mg/kg). Vinpocetine and geraniol, comparable to gliclazide, amended the deteriorated renal function and histopathological alterations. They exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-Ý1 (TGF-Ý1).Vinpocetine and geraniol modulated the endothelial dysfunction as well.They also restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase (NADPH oxidase) and enhancing the antioxidant moieties, superoxide dismutase (SOD) and reduced glutathione (GSH). These beneficial effects were associated with a robust down regulation of microRNA-21 (miRNA-21) and consequently, reversion of tumor suppressor protein phosphatase and tension homolog(PTEN) /Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. This resulted in pronounced anti-inflammatory and anti-apoptic effects. Vinpocetine and geraniol, similar to gliclazide, also induced up-regulation of hypoxia inducible factor-1Ü (HIF-1Ü).The current study indicates that vinpocetine and geraniol, comparable to gliclazide, interfere with miRNA-21/PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in DN