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976560 
Journal Article 
Abstract 
MnTBAP selectively scavenges peroxynitrite over superoxide: Comparison of MnTBAP to MnTE-2-PyP in two different models of oxidative stress injuries, SOD-specific E-coli model and carrageenan-induced pleurisy 
Batinic-Haberle, I; Cuzzocrea, S; Reboucas, JS; Ferrer-Sueta, G; Mazzon, E; Di Paola, R; Radi, R; Sposojevic, I; Benov, L; Salvemini, D 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S79-S79 
English 
WOS:000260867900220 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
MnTBAP is referred to as an SOD mimic in numerous models of oxidative stress. Yet, pure MnTBAP does not, while commercial/ill-purified samples do dismute O2•− via Mn-containing impurities. Herein, we show that neither commercial nor pure MnTBAP substitute for SOD enzyme in the SOD-specific system, SOD-deficient E. coli model, while MnTE-2-PyP-treated SOD-deficient E. coli grew as well as wild-type strain. in carrageenan-induced pleurisy in mice, inflammation was evidenced by increased pleural fluid exudate, and neutrophil infiltration and activation: these events were blocked by 0.3 mg/kg of MnTE-2-PyP and to a slightly lesser extent with 10 mg/kg of either MnTBAP. Also, 3-nitrotyrosine formation was blocked by both compounds; again MnTE-2-PyP was 33-fold more effective. Pleurisy model data indicate that MnTBAP exert some protective actions in common with MnTE-2-PyP, which are not O2•−-related, and can be fully rationalized if one considers that the common biological role shared by MnTBAP and MnTE-2-PyP is related to their reduction of peroxynitrite and carbonate radical. The log kcat (O2•−) for MnTBAP of ~3.16 is ~5 and ~7 orders of magnitude smaller than the SOD activity of the potent SOD mimic MnTE-2-PyP and Cu,Zn-SOD, respectively. Peroxynitrite scavenging ability of MnTBAP, however, is only ~2.5 orders of magnitude smaller than that of MnTE-2-PyP and is not significantly affected by the presence of the SOD-active impurities in commercial MnTBAP sample (log kred(ONOO–) = 5.06 for pure and 4.97 for commercial sample).The reduction of carbonate radical is equally fast with MnTBAP and MnTE-2-PyP. the dose of MnTBAP required to yield oxidative stress protection and block nitrotyrosine formation in the pleurisy model is >1.5 orders of magnitude higher than that of MnTE-2-PyP, which could be related to the smaller ability of MnTBAP to scavenge peroxynitrite. These observations have profound biological repercussions as they may suggest that the effect of MnTBAP observed in numerous studies may conceivably relate to peroxynitrite scavenging and that pure MnTBAP may prove valuable to distinguish ONOO–/CO3•− from O2•− pathways. DS and IBH acknowledge NIH R01 DA024074, IS DUCCC Core grant 5-P30-CA14236-29, and IBH NIAID grant 5-U19-AI067798-03. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008