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

Salvatore Cuzzocrea, Giuseppina Costantino, Emanuela Mazzon, Angela De Sarro, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1241-1251
Number of pages11
JournalBritish Journal of Pharmacology
Volume128
Issue number6
Publication statusPublished - 1999

Keywords

  • Cell injury
  • Inflammation
  • MnTBAP
  • Multiple organ failure
  • Myeloperoxidase
  • Nitric oxide
  • Nitrotyrosine
  • Peroxynitrite
  • SOD mimetic
  • Zymosan-induced shock

ASJC Scopus subject areas

  • Pharmacology

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