{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:30:22Z","timestamp":1773459022414,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4416,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1997,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Peroxynitrite is a toxic oxidant species produced from nitric oxide (NO) and superoxide. We have recently observed that the cell\u2010permeable superoxide dismutase mimetic Mn(III)tetrakis(4\u2010benzoic acid) porphyrin (MnTBAP) inhibits the suppression of mitochondrial respiration elicited by authentic peroxynitrite <jats:italic>in vitro<\/jats:italic>. Here we have investigated the relative potency of MnTBAP and a range of related compounds in terms of inhibition of peroxynitrite\u2010induced oxidation and cytotoxicity. In addition, we tested the effects of MnTBAP on the vascular and the cellular energetic failure in rodent models of endotoxic shock.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We observed a dose\u2010related inhibition of the peroxynitrite\u2010induced oxidation of dihydrorhodamine 123 to rhodamine by MnTBAP, ZnTBAP and FeTBAP, but not by MnTMPyP [(5,10,15,20\u2010tetrakis(N\u2010methyl\u20104\u2032\u2010pirydyl)porphinato)\u2010manganese (III)]. In addition, MnTBAP, ZnTBAP and FeTBAP, but not MnTMPyP prevented the suppression of mitochondrial respiration by authentic peroxynitrite in cultured J774 macrophages.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In rat cultured aortic smooth muscle cells, MnTBAP protected against the suppression of mitochondrial respiration in response to authentic peroxynitrite, immunostimulation and nitric oxide (NO) donor compounds. MnTBAP slightly reduced the amount of nitrite\/nitrate produced in response to immunostimulation in these cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Administration of MnTBAP, 15 mg kg<jats:sup>\u22121<\/jats:sup> i.v., before the administration of endotoxin (15 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) to rats ameliorated the development of vascular hyporeactivity and the development of endothelial dysfunction in the thoracic aorta <jats:italic>ex vivo<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MnTBAP also prevented the endotoxin\u2010induced decrease in mitochondrial respiration, the development of DNA single strand breaks, and the depletion of intracellular NAD<jats:sup>+<\/jats:sup> in peritoneal macrophages <jats:italic>ex vivo<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MnTBAP did not inhibit the expression by endotoxin of the inducible NO synthase in lung samples.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MnTBAP did not alter survival rate in mice challenged with high dose endotoxin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our findings, taken together with previous data demonstrating protective effects of NO synthase inhibitors against the endotoxin\u2010induced contractile and energetic failure in the models of shock used in the current study, and with the known ability of peroxynitrite to cause cellular energy depletion, suggest a role for peroxynitrite in the pathogenesis of cellular energetic failure and contractile dysfunction in endotoxin shock.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>120<\/jats:bold>, 259\u2013267; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0700872\">10.1038\/sj.bjp.0700872<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0700872","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T16:05:00Z","timestamp":1156521900000},"page":"259-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":192,"title":["The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock"],"prefix":"10.1111","volume":"120","author":[{"given":"Basilia","family":"Zingarelli","sequence":"first","affiliation":[]},{"given":"Brian J","family":"Day","sequence":"additional","affiliation":[]},{"given":"James D","family":"Crapo","sequence":"additional","affiliation":[]},{"given":"Andrew L","family":"Salzman","sequence":"additional","affiliation":[]},{"given":"Csaba","family":"Szab\u00f3","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1620"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1995.1044"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-79130-7_7"},{"key":"e_1_2_7_5_1","article-title":"A metalloporphyrin superoxide dismutase mimetic protects against paraquat\u2010induced lung injury in vivo","volume":"139","author":"Day D.J.","year":"1996","journal-title":"Toxicol. 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