INO-4885 [5,10,15,20-tetra[N-(benzyl-4'-carboxylate)-2-pyridinium]-21H,23H-porphine iron(III) chloride], a peroxynitrite decomposition catalyst, protects the heart against reperfusion injury in mice.
INO-4885 [5,10,15,20-tetra[N-(benzyl-4'-carboxylate)-2-pyridinium]-21H,23H-porphine iron(III) chloride], a peroxynitrite decomposition catalyst, protects the heart against reperfusion injury in mice.
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DOI：
10.1124/jpet.108.144352
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Tao L
中科院分区：
文献类型：
--
作者：
Jiao XY;Gao E;Yuan Y;Wang Y;Lau WB;Koch W;Ma XL;Tao L
Oxidative/nitrative stress caused by peroxynitrite, the reaction product of superoxide 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]-21H,23H-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, 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 (p < 0.01), and reduced tissue nitrotyrosine content (p < 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 N-(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 production.
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影响因子：
4.8
作者：
Cuzzocrea, S;Misko, TP;Salvemini, D
通讯作者：
Salvemini, D
影响因子：
37.8
作者：
Lund, DD;Faraci, FM;Heistad, DD
通讯作者：
Heistad, DD
影响因子：
4.1
作者：
Lymar, SV;Hurst, JK
通讯作者：
Hurst, JK
影响因子：
7.3
作者：
Thiyagarajan, M;Kaul, CL;Sharma, SS
通讯作者：
Sharma, SS
DOI：
10.1186/1471-2210-4-20
发表时间：
2004-09-30
期刊：
BMC Pharmacology
影响因子：
--
作者：
Chirino, Yolanda I.;Hernandez-Pando, Rogelio;Pedraza-Chaverri, Jose
通讯作者：
Pedraza-Chaverri, Jose