論文

査読有り
2014年5月

Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts

BIOLOGICAL & PHARMACEUTICAL BULLETIN
  • Tatsuya Muto
  • Haruki Usuda
  • Aya Yamamura
  • Koji Yoshida
  • Ai Ohashi
  • Kumiko Mitsui-Saitoh
  • Junichi Sakai
  • Yumi Sugimoto
  • Hideki Mizutani
  • Tsunemasa Nonogaki
  • Yoshihiro Hotta
  • 全て表示

37
5
開始ページ
731
終了ページ
739
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/bpb.b13-00552
出版者・発行元
PHARMACEUTICAL SOC JAPAN

Serotonin (5-hydroxytryptamine; 5-HT) is known to be activated during ischemia-reperfusion and triggers contractile dysfunction and pathological apoptosis. Here, the beneficial effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine was demonstrated on ischemia-reperfusion injury in guinea-pig hearts perfused using the Langendorff technique. The recovery (%) of left ventricular developed pressure (LVDP) by fluvoxamine (5x10(-8) M) was 95.4% (control: 32%), which was consistent with the inhibition of mitochondrial Ca2+([Ca2+](m)) uptake induced by changes in the Ca2+ content and acidification of the perfusate, and similar to reperfusion following global ischemia in Langendorff-perfused hearts. Fluvoxamine inhibited the increase in [Ca2+](m) induced by changes in the Ca2+ content of the perfusate in perfused preparations of mitochondria, which was similar to the results obtained with the mitochondrial permeability transition pore (MPTP) opener atractyroside. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly less in fluvoxamine-treated hearts than in control hearts, with decreases in caspase-3 activity. These results suggest that SSRI inhibits opening of the MPTP by preventing [Ca2+](m) overload-induced apoptosis related to the endogenous accumulation of 5-HT in ischemia-reperfusion hearts.

リンク情報
DOI
https://doi.org/10.1248/bpb.b13-00552
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000335273700003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1248/bpb.b13-00552
  • ISSN : 0918-6158
  • Web of Science ID : WOS:000335273700003

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