{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:28:59Z","timestamp":1773293339329,"version":"3.50.1"},"reference-count":108,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2408,"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":[[2002,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Myocardial injury caused by ischaemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, mast cell activation, and peroxidation of cell membrane lipids. These events are followed by myocardial cell alterations resulting eventually in cell necrosis. An enhanced formation of reactive oxygen species is widely accepted as a stimulus for tissue destruction and cardiac failure.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study, we have investigated the cardioprotective effects of M40403 in myocardial ischaemia\u2010reperfusion injury. M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that selectively removes superoxide anion. Ischaemia was induced in rat hearts <jats:italic>in vivo<\/jats:italic> by ligating the left anterior descending coronary artery. Thirty minutes after the induction of ischaemia, the ligature was removed and reperfusion allowed to occur for at least 60 min. M40403 (0.1\u20131 mg kg<jats:sup>\u22121<\/jats:sup>) was given intravenously 15 min before ischaemia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results obtained in this study showed that M40403 significantly reduced the extent of myocardial damage, mast cell degranulation and the incidence of ventricular arrhythmias. Furthermore, M40403 significantly attenuated, in a dose\u2010dependent manner, neutrophil infiltration in the myocardium as well as the associated induction of lipid peroxidation. Calcium overload seen post\u2010reperfusion of the ischaemic myocardium was also reduced by M40403.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Immunohistochemical analysis for nitrotyrosine revealed a positive staining in cardiac tissue taken after reperfusion: this was attenuated by M40403. Moreover reperfused cardiac tissue sections showed positive staining for P\u2010selectin and for anti\u2010intercellular adhesion molecule (ICAM\u20101) in the vascular endothelial cells. M40403 treatment markedly reduced the intensity and degree of P\u2010selectin and ICAM\u20101 in these tissues. No staining for nitrotyrosine, P\u2010selectin or ICAM\u20101 was found in cardiac tissue taken at the end of the ischaemic period.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Overall, M40403 treatment reduced the morphological signs of myocardial cell injury and significantly improved survival.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Taken together, these results clearly indicate that M40403 treatment exerts a protective effect against ischaemia\u2010reperfusion\u2010induced myocardial injury, supporting a key role for superoxide anion in reperfusion injuries. This suggests that synthetic enzymes of SOD such as M40403, offer a novel therapeutic approach for the treatment of ischaemic heart disease where superoxide anion plays a dominant role.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>136<\/jats:bold>, 905\u2013917. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704774\">10.1038\/sj.bjp.0704774<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704774","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T21:36:01Z","timestamp":1027892161000},"page":"905-917","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury <i>in vivo<\/i>"],"prefix":"10.1111","volume":"136","author":[{"given":"Emanuela","family":"Masini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Mazzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo","family":"Marzocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Francesco","family":"Mannaioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Salvemini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3570593"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00052564"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2580617"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic000958v"},{"key":"e_1_2_7_6_1","first-page":"1367","article-title":"Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart","volume":"152","author":"BANI D.","year":"1998","journal-title":"Am. 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