RESUMO
BACKGROUND: Stem cell therapy holds a great promise for the repair of injured tissues and organs, including the kidney. We studied the effect of mesenchymal stem cells (MSC) on experimental diabetic nephropathy (DN) in rats and the possible paracrine signals that mediate their action. MATERIALS AND METHODS: Rats were divided into controls, DN rats, DN rats receiving MSCs. MSCs were given in a dose of (106cells) by intravenous injection. After 4 weeks, 24 h urinary albumin, serum urea and creatinine concentrations, transforming growth factor ß (TGF ß), tumor necrosis factor α (TNFα), B-cell lymphoma 2 (bcl2) and Bax gene expression and vascular endothelial growth factor (VEGF) were assessed. Histopathology staining was performed. RESULTS: MSC therapy significantly improved 24 h urinary albumin, serum urea and creatinine concentrations, increased angiogenic growth factor VEGF, and anti-apoptotic protein bcl2 while decreased the pro-inflammatory TNF-α, fibrogenic growth factor TGF ß, and pro-apoptotic protein Bax. The histopathology examination showed patchy areas of minimal necrosis and degeneration in renal tubules.
RESUMO
BACKGROUND: Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. MATERIALS AND METHODS: Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. RESULTS: NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin.
