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Beneficial effects of Mn(III)tetrakis (4‐benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in zymosan‐induced shock
Author(s) -
Cuzzocrea Salvatore,
Costantino Giuseppina,
Mazzon Emanuela,
De Sarro Angela,
Caputi Achille P
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702826
Subject(s) - zymosan , peroxynitrite , chemistry , superoxide dismutase , superoxide , pharmacology , in vivo , biochemistry , microbiology and biotechnology , oxidative stress , biology , in vitro , enzyme
The therapeutic efficacy of Mn(III)tetrakis (4‐benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase mimetic which scavenges peroxynitrite, was investigated in rats subjected to shock induced by peritoneal injection of zymosan. Our data show that MnTBAP (given at 1, 3 and 10 mg kg −1 intraperitoneally, 1 and 6 h after zymosan injection) significantly reduce in dose dependent manner the development of peritonitis (peritoneal exudation, high nitrate/nitrite and peroxynitrite plasma levels, leukocyte infiltration and histological examination). Furthermore, our data suggest that there is a reduction in the lung, small intestine and liver myeloperoxidase (MPO) activity and lipid peroxidation activity from MnTBAP‐treated rats. MnTBAP also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage and reduction of cellular levels of NAD + was observed in ex vivo macrophages harvested from the peritoneal cavity of zymosan‐treated rat.In vivo treatment with MnTBAP significantly reduced in a dose‐dependent manner peroxynitrite formation and prevented the appearance of DNA damage, the decrease in mitochondrial respiration and the loss of cellular levels of NAD + . In conclusion our results showed that MnTBAP was effective in preventing the development of zymosan‐induced shock.British Journal of Pharmacology (1999) 128 , 1241–1251; doi: 10.1038/sj.bjp.0702826