2014年5月
Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts
BIOLOGICAL & PHARMACEUTICAL BULLETIN
- 巻
- 37
- 号
- 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
- ID情報
-
- DOI : 10.1248/bpb.b13-00552
- ISSN : 0918-6158
- Web of Science ID : WOS:000335273700003