PMID: 16644677Apr 29, 2006Paper

2-(8-hydroxy-6-methoxy-1-oxo-1h-2-benzopyran-3-yl) propionic acid, an inhibitor of angiogenesis, ameliorates renal alterations in obese type 2 diabetic mice

Diabetes
K IchinoseHirofumi Makino

Abstract

One of the mechanisms involved in the progression of diabetic nephropathy, the most common cause of end-stage renal failure, is angiogenic phenomenon associated with the increase of angiogenic factors such as vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-2, an antagonist of Ang-1. In the present study, we examined the therapeutic efficacy of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3), a small molecule isocoumarin with antiangiogenic activity, using diabetic db/db mice, a model of obese type 2 diabetes. Increases in kidney weight, glomerular volume, creatinine clearance, urinary albumin excretion, total mesangial fraction, glomerular type IV collagen, glomerular endothelial area (CD31(+)), and monocyte/macrophage accumulation (F4/80(+)) observed in control db/db mice were significantly suppressed by daily intraperitoneal injection of NM-3 (100 mg/kg, for 8 weeks). Increases in renal expression of VEGF-A, Ang-2, fibrogenic factor transforming growth factor (TGF)-beta1, and chemokine monocyte chemoattractant protein-1 but not tumor necrosis factor-alpha were also inhibited by NM-3 in db/db mice. Furthermore, decreases of nephrin mRNA and protein levels in db/db mice were recovered...Continue Reading

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