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• W2166085923 abstract "Oxidative/nitrative stress caused by peroxynitrite, the reaction product of superoxide ( (mathrm{O}_{2}^{overline{.}}) ) and nitric oxide (NO), is the primary cause of myocardial ischemia/reperfusion injury. The present study determined whether INO-4885 [5,10,15,20-tetra[N-(benzyl-4′-carboxylate)-2-pyridinium]-21<i>H</i>,23<i>H</i>-porphine iron(III) chloride], a new peroxynitrite decomposition catalyst, may provide cellular protection and protect heart from myocardial ischemia/reperfusion injury. Adult male mice were subjected to 30 min of ischemia and 3 or 24 h of reperfusion. Mice were randomized to receive vehicle, INO-4885 without catalytic moiety, or INO-4885 (3-300 μg/kg i.p.) 10 min before reperfusion. Infarct size, apoptosis, nitrotyrosine content, NO/ (mathrm{O}_{2}^{overline{.}}) production, and inducible nitric-oxide synthase (iNOS)/NADPH oxidase expression were determined. INO-4885 treatment reduced ischemia/reperfusion-induced protein nitration and caspase 3 activation in a dose-dependent fashion in the range of 3 to 100 μg/kg. However, doses exceeding 100 μg/kg produced nonspecific effects and attenuated its protective ability. At the optimal dose (30 μg/kg), INO-4885 significantly reduced infarct size (p < 0.01), decreased apoptosis (<i>p</i> < 0.01), and reduced tissue nitrotyrosine content (<i>p</i> < 0.01). As expected, INO-4885 had no effect on ischemia/reperfusion-induced iNOS expression and NO overproduction. To our surprise, this compound significantly reduced superoxide production and partially blocked NADPH oxidase overexpression in the ischemic/reperfused cardiac tissue. Additional experiments demonstrated that INO-4885 provided better cardioprotection than <i>N</i>-(3-(aminomethyl)benzyl)acetamidine (1400W, a selective iNOS inhibitor), apocynin (an NADPH oxidase inhibitor), or Tiron (a cell-permeable superoxide scavenger). Taken together, our data demonstrated that INO-4885 is a cardioprotective molecule that attenuates myocardial reperfusion injury by facilitating peroxynitrite decomposition and inhibiting NADPH oxidase-derived (mathrm{O}_{2}^{overline{.}}) production." @default.
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• W2166085923 date "2008-11-25" @default.
• W2166085923 modified "2023-10-17" @default.
• W2166085923 title "INO-4885 [5,10,15,20-Tetra[<i>N</i>-(benzyl-4′-carboxylate)-2-pyridinium]-21<i>H</i>,23<i>H</i>-porphine Iron(III) Chloride], a Peroxynitrite Decomposition Catalyst, Protects the Heart against Reperfusion Injury in Mice" @default.
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• W2166085923 doi "https://doi.org/10.1124/jpet.108.144352" @default.
• W2166085923 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2663530" @default.
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