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 (MnTBAP), a novel superoxide dismutase mimetic which scavenges peroxynitrite, was investigated in rats subjected to shock induced by peritoneal injection of zymosan. 2 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). 3 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. 4 MnTBAP also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. 5 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. 6 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+. 7 In conclusion our results showed that MnTBAP was effective in preventing the development of zymosan-induced shock.
Cuzzocrea
S
S
Institute of Pharmacology, School of Medicine, University of Messina, Policlinico Universitario, 98122 Messina, Italy. salvator@imeuniv.unime.it
Costantino
G
G
Mazzon
E
E
De Sarro
A
A
Caputi
A P
AP
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001663:Bilirubin / Q000097:blood; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D008168:Lung / Q000737:chemistry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D009243:NAD / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D015054:Zymosan / Q000009:adverse effects*
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D009566:Nitrates; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D009243:NAD; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D015054:Zymosan; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin