{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:37:52Z","timestamp":1791337072126,"version":"4.3.1"},"reference-count":37,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:p>Reperfusion after a period of ischemia is associated with the formation of reactive oxygen species (ROS) and Ca<jats:sup>2+<\/jats:sup>overload resulting in the opening of a nonspecific pore in the inner membrane of the mitochondria, called the mitochondrial permeability transition pore (PTP), leading to cell damage. Although endogenous antioxidants are activated because of oxidative stress following ischemia, their levels are not high enough to prevent reperfusion injury. Hence there is always a need for exogenous supplement of antioxidants, especially after acute ischemia. Here we demonstrated the effects of the antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) in preventing reperfusion injury of the heart by inhibition of PTP opening. Ischemia (30 min) by left coronary artery (LCA) occlusion and reperfusion (120 min) in Wistar rats after pretreatment with MCI-186 (10 mg\/kg iv) infusion starting from 30 min before LCA occlusion resulted in 1) less area of myocardial infarction (19.2% vs. 61.6%), 2) well-maintained myocardial ATP content ( P &lt; 0.03 vs. control), 3) decreased mitochondrial swelling and reduced cytochrome c release, 4) increased expression of BCl-2, 5) lower prevalence of apoptotic cells (14.3% vs. 2.9%), and 6) reduced DNA fragmentation in the MCI-186-treated group. These cytoprotective effects of MCI-186 were inhibited on opening PTP before MCI-186 treatment with the PTP activators lonidamine (10 mg\/kg iv) or atractyloside (5 mg\/kg iv) but failed to inhibit the protective effects exerted by another antioxidant, allopurinol, suggesting that the PTP inhibiting property is specific for MCI-186. These results demonstrate that the radical scavenger MCI-186, by inhibiting the opening of the PTP, prevents necrosis and cytochrome c release and hence pathological apoptosis.<\/jats:p>","DOI":"10.1152\/ajpheart.00143.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:13:37Z","timestamp":1425413617000},"page":"H2171-H2178","source":"Crossref","is-referenced-by-count":83,"title":["Antioxidant MCI-186 inhibits mitochondrial permeability transition pore and upregulates Bcl-2 expression"],"prefix":"10.1152","volume":"285","author":[{"given":"Katare Gopalrao","family":"Rajesh","sequence":"first","affiliation":[{"name":"Department of Surgery II, Kochi Medical School, Kohasu, Nankoku, Kochi 7838505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Sasaguri","sequence":"additional","affiliation":[{"name":"Department of Surgery II, Kochi Medical School, Kohasu, Nankoku, Kochi 7838505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Surgery II, Kochi Medical School, Kohasu, Nankoku, Kochi 7838505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Surgery II, Kochi Medical School, Kohasu, Nankoku, Kochi 7838505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.6.6060"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204953"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1042\/bj3410233"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(78)57003-1"},{"key":"REF5","doi-asserted-by":"crossref","unstructured":"Dhalla NS, Elmoselhi AB, Hata T, and Makino N.Status of myocardial antioxidants in ischemia-reperfusion injury.Cardiovasc Res1847: 446\u2013456, 2000.","DOI":"10.1016\/S0008-6363(00)00078-X"},{"key":"REF6","doi-asserted-by":"crossref","unstructured":"Dhalla NS, Panagia V, Singal PK, Makino N, Dixon IM, and Eyolfson DA.Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury.J Mol Cell Cardiol20,Suppl2: 3\u201313, 1988.","DOI":"10.1016\/0022-2828(88)90327-6"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3653"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1987.253.5.H1026"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63020584.x"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.41.139"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.61.5.757"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(96)90580-9"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4507"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1042\/bss0660181"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00122-4"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(97)00454-2"},{"key":"REF17","unstructured":"Hopson SB, Lust RM, Sun YS, Zeri RS, Morrison RF, Otaki M, and Chitwood WR Jr.Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model.J Natl Med Assoc87: 480\u2013484, 1995."},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1016\/S1052-3057(98)80049-9"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.56.2.262"},{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00724.x"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1038\/35004069"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.3109\/10715769609088034"},{"key":"REF23","unstructured":"Mitsumori K, Sakuragi M, Kitami K, Koyanagi I, and Murata J.The effect of MCI-186 on regional cerebral blood flow in patients with acute cerebral infarction.Therapeut Res19: 553\u2013565, 1998."},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(01)00132-6"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1990.tb42289.x"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1038\/35065201"},{"key":"REF27","doi-asserted-by":"crossref","unstructured":"Palmer JW, Tandler B, and Hoppel CL.Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac cells.J Biol Chem252: 8731\u20138739, 1977.","DOI":"10.1016\/S0021-9258(19)75283-1"},{"key":"REF28","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(02)03459-0"},{"key":"REF29","doi-asserted-by":"publisher","DOI":"10.1038\/35160"},{"key":"REF30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.tb19049.x"},{"key":"REF31","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.5.581"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1002\/bio.1170070202"},{"key":"REF33","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(00)00102-9"},{"key":"REF34","unstructured":"Watanabe T, Yuki S, Egawa M, and Nishi H.Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.J Pharmacol Exp Ther268: 1597\u20131604, 1994."},{"key":"REF35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.2.H899"},{"key":"REF36","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(95)00003-A"},{"key":"REF37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00250.2002"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00143.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T09:16:17Z","timestamp":1651396577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00143.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,11]]}},"alternative-id":["10.1152\/ajpheart.00143.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00143.2003","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11]]}}}