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• W2149097174 abstract "Cyclooxygenase (COX)-2 expression is increased in the kidney of rats made diabetic with streptozotocin and associated with enhanced release of prostaglandins stimulated by arachidonic acid (AA). Treatment of diabetic rats with nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase or with tempol to reduce superoxide prevented these changes, suggesting the possibility that peroxynitrite (ONOO) may be the stimulus for the induction of renal COX-2 in diabetes. Consequently, we tested the effects of an ONOO decomposition catalyst, 5,10,15,20-tetrakis( N-methyl-4′-pyridyl)porphyrinato iron(III) (FeTMPyP), which was administered for 3–4 wk after the induction of diabetes. FeTMPyP treatment normalized the twofold increase in the expression of nitrotyrosine, a marker for ONOO formation, in the diabetic rat and prevented the increase in renal COX-2 expression without modifying the two- to threefold increases in renal release of prostaglandins PGE 2 and 6-ketoPGF 1α in response to AA. FeTMPyP treatment of diabetic rats reduced the elevated creatinine clearance and urinary excretion of TNF-α and transforming growth factor (TGF)-β, suggesting a renoprotective effect. Double immunostaining of renal sections and immunoprecipitation of COX-2 and nitrotyrosine suggested nitration of COX-2 in diabetic rats. In cultured human umbilical vein endothelial cells (HUVECs) exposed to elevated glucose (450 mg/dl) or ONOO derived from 3-morpholinosydnonimine (SIN-1), expression of COX-2 was increased and was prevented when endothelial cells were treated with FeTMPyP. These results indicate that elevated glucose increases the formation of ONOO, which contributes to the induction of renal COX-2 in the diabetic rat." @default.
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• W2149097174 date "2011-03-01" @default.
• W2149097174 modified "2023-09-25" @default.
• W2149097174 title "Treatment of diabetic rats with a peroxynitrite decomposition catalyst prevents induction of renal COX-2" @default.
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• W2149097174 doi "https://doi.org/10.1152/ajpheart.00768.2010" @default.
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