Part I: Pathogenetic Role of Peroxynitrite in the Development of Diabetes and Diabetic Vascular Complications: Studies With FP15, A Novel Potent Peroxynitrite Decomposition Catalyst

• DOI: 10.1007/bf03402167
• Publication Date: 2018-09-13T03:57:26Z
• Authors: Csaba Szabó; Jon G. Mabley; Suzanne M. Moeller; Roman Shimanovich; Pál Pacher; László Virág; Francisco G. Soriano; John H. Van Duzer; William Williams; Andrew L. Salzman; John T. Groves
• Keywords: Peroxynitrous acid; Nitrotyrosine; Pancreatic Islets

Peroxynitrite is a cytotoxic oxidant formed from nitric oxide (NO) and superoxide. Tyrosine nitration, footprint of peroxynitrite, has been demonstrated in the pancreatic islets as well cardiovascular system diabetic subjects. Delineation pathogenetic role peroxynitrite disease conditions requires use potent, vivo active decomposition catalysts. The aim current work was to produce potent catalyst test its effects rodent models diabetes complications. FP15 synthesized analyzed using standard chemical methods. Diabetes triggered by administration streptozotocin. nitration measured immunohistochemically. Cardiovascular vascular measurements were conducted according physiologic FP15, porphyrinic catalyst, potently inhibited tyrosine peroxynitrite-induced cytotoxicity vitro vivo. treatment (3–10 mg/kg/d) dose dependently reduced incidence severity mellitus rats subjected multiple low doses streptozotocin, nonobese mice developing spontaneous autoimmune diabetes. Furthermore, with protected against development dysfunction (loss endothelium-dependent relaxations) cardiac my-ocardial contractility) mice. islets. results demonstrate importance endogenous generation pathogenesis catalysts may be therapeutic utility other pathophysiologic conditions.