Peroxynitrite plays a key role in glomerular lesions in diabetic rats.

BACKGROUND: Oxidative stress plays a crucial role in chronic complications of diabetes such as diabetic nephropathy (DN), the main cause of renal failure. In diabetes, whether peroxynitrite (ONOO(-)), generated from inducible nitric oxide synthase (iNOS) induced by tumor necrosis factor alpha (TNF-alpha), plays a primary role in the pathogenesis of glomerular lesion is not yet fully known. This study was designed to investigate the role of exaggerated ONOO(-) in glomerular lesions of diabetic rats.

METHODS: Diabetes was induced in Sprague Dawley rats by an intraperitoneal injection of streptozocin, and aminoguanidine was used as selective inhibitor of iNOS. The iNOS transcription and protein distribution and content in rat glomeruli were detected. Nitrotyrosine (NT), a specific marker of ONOO(-), was measured to represent the distribution and content of ONOO(-) in rat glomeruli. TNF-alpha level and nitric oxide (NO) content were evaluated, and the pathological changes in the rat glomeruli were observed. Biochemical indicators of renal function were also measured.

RESULTS: TNF-alpha level and NO content, iNOS expression and its protein content, and NT content increased significantly, in accordance with the pathological changes of glomerulus and renal dysfunction in the diabetes group. Aminoguanidine was found to inhibit iNOS and then reduce ONOO(-) overformation, attenuating the pathological alterations.

CONCLUSION: This study clarified clearly that exaggerated ONOO(-) formation, generated from induced iNOS may play a key role in glomerular lesions in diabetic rats.