Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP),a superoxide dismutase mimetic, in zymosan-induced shock

1 The therapeutic efficacy of Mn(III)tetrakis (4-benzoic acid) porphyrin (M nTBAP), a novel superoxide dismutase mimetic which scavenges peroxynitrite, was investigated in rats subjected to shock induced by peritoneal injectio n of zymosan. 2 Our data show that MnTBAP (given at 1, 3 and 10 mg kg(-1) intraperitoneal ly, 1 and 6 h after zymosan injection) significantly reduce in dose depende nt manner the development of peritonitis (peritoneal exudation, high nitrat e/nitrite and peroxynitrite plasma levels, leukocyte infiltration and histo logical examination). 3 Furthermore, our data suggest that there is a reduction in the lung, smal l intestine and liver myeloperoxidase (MPO) activity and lipid peroxidation activity from MnTBAP-treated rats. 4 MnTBAP also reduced the appearance of nitrotyrosine immunoreactivity in t he inflamed tissues. 5 Furthermore, a significant reduction of suppression of mitochondrial resp iration, DNA strand breakage and reduction of cellular levels of NAD(+) was observed in ex vivo macrophages harvested from the peritoneal cavity of zy mosan-treated rat. 6 In vivo treatment with MnTBAP significantly reduced in a dose-dependent m anner peroxynitrite formation and prevented the appearance of DNA damage, t he decrease in mitochondrial respiration and the loss of cellular levels of NAD(+). 7 In conclusion our results showed that MnTBAP was effective in preventing the development of zymosan-induced shock.