Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor

Yaoita, Hiroyuki; Ogawa, Kaoru; Maehara, Kazuhira; Maruyama, Yukio

doi:10.1161/01.cir.97.3.276

Cited by 579 publications

(354 citation statements)

References 14 publications

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“…Previous studies have shown that application of caspase inhibitors prior to ischaemia confers protection against ischaemia-reperfusion injury in myocardium. For example, Z-VAD×fmk administered before, and continuously during and after an ischaemic insult resulted in better recovery and a smaller infarct size in rat heart in vivo (Yaoita et al, 1998). Holly et al (1999) have reported that caspase inhibition with the non-selective inhibitor Y-VAD×cmk prior to coronary artery occlusion in the rabbit heart in vivo led to limitation of infarct size.…”

mentioning

confidence: 99%

Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury

Mocanu

Baxter

Yellon

2000

British J Pharmacology

194

105

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Ischaemia-reperfusion injury causes cell death by both necrosis and apoptosis. Caspase activation is a major event in apoptosis. We therefore examined the e ect of caspase inhibitors during reperfusion upon myocardial infarction. Rat isolated hearts were subjected to 35 min coronary occlusion and 120 min reperfusion. Treatment groups were perfused with caspase inhibitors during early reperfusion. We assessed a non-selective caspase inhibitor (Z-VAD×fmk, 0.1 mM), a caspase-8 inhibitor (Z-IETD×fmk, 0.07 mM), a caspase-9 inhibitor (Z-LEHD×fmk, 0.07 mM) and a caspase-3 inhibitor (Ac-DEVD×cmk, 0.07 mM). All caspase inhibitors limited infarct size (infarct-risk ratio per cent: control 38.5+2.6; Z-VAD×fmk 24.6+3.4; Z-LEHD×fmk 19.3+2.4; Z-IETD×fmk 23.0+5.4; AcDEVD×cmk 27.8+3.3; P50.05 when compared with control value, 1-way ANOVA). We conclude that caspase inhibition during early reperfusion protects myocardium against lethal reperfusion injury.

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mentioning

confidence: 99%

Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury

Mocanu

Baxter

Yellon

2000

British J Pharmacology

194

105

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“…The Fas receptor (APO-1or CD-95) binds to FasL, Caspases can be inhibited by the apoptosis inhibitory protein (AIP), which can be displaced by the second activator of caspase-derived mitochondria (SMAC) [26]. Caspase inhibitors are being studied in an attempt to reduce the inflammatory response in models of cardiac ischemiareperfusion in rats [28]. In this sense, for example, preliminary results show that intravenous administration of Z-Val-Ala-DL-Asp-fluorometilquetone (ZVAD-fmk) has contributed at least partially, to the attenuation of apoptosis of cardiomyocytes [28].…”

Section: Apoptosismentioning

confidence: 99%

“…Caspase inhibitors are being studied in an attempt to reduce the inflammatory response in models of cardiac ischemiareperfusion in rats [28]. In this sense, for example, preliminary results show that intravenous administration of Z-Val-Ala-DL-Asp-fluorometilquetone (ZVAD-fmk) has contributed at least partially, to the attenuation of apoptosis of cardiomyocytes [28].…”

Section: Apoptosismentioning

confidence: 99%

Os leucócitos e a resposta inflamatória na lesão de isquemia-reperfusão

Francischetti¹,

Moreno²,

Scholz³

et al. 2010

Rev Bras Cir Cardiovasc

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The events of ischemia-reperfusion injury trigger a systemic inflammatory response that can lead to cellular damage and even organ failure. Such effects are noted in the post-operative recovery, especially with the use of cardiopulmonary bypass. Nowadays, we know that leukocytes play an important role in this process. Therefore, this study addresses the role of leukocytes in the pathophysiology of ischemia-reperfusion injury and activation of inflammatory cascades through this process and seeks to help in understanding these mechanisms as well as bringing contributions on the therapeutic approaches that may mitigate them. This retrospective review was performed from scientific papers published over the past ten years, in Portuguese and English, indexed in international databases of Medline, SciELO and related classical texts. The descriptors investigated were: ischemiareperfusion, leukocytes, inflammatory response, cardiopulmonary bypass, adverse effects and apoptosis.Keywords: Cardiopulmonary bypass. Leukocytes. Ischemia. Reperfusion injury. ResumoOs eventos de isquemia-reperfusão desencadeiam uma resposta inflamatória sistêmica que pode levar a lesões celulares e até falência de órgãos. Tais repercussões são notadas no pós-operatório de cirurgias, em especial, com o uso de circulação extracorpórea. Sabe-se, atualmente, que os leucócitos exercem importante papel neste processo. Assim, este estudo aborda o papel dos leucócitos na fisiopatologia das lesões de isquemia-reperfusão e a ativação das cascatas inflamatórias por esse processo e procura auxiliar na compreensão destes mecanismos assim como trazer contribuições acerca das abordagens terapêuticas que possam atenuá-los. Esta revisão bibliográfica retrospectiva foi realizada a partir de documentos científicos publicados nos últimos dez anos, em português e inglês, indexados em bases de dados internacionais Medline e SciELO e de textos clássicos relacionados. Os descritores pesquisados foram: isquemia-reperfusão, leucócitos, resposta inflamatória, circulação extracorpórea, efeitos adversos e apoptose.Descritores: Circulação extracorpórea. Leucócitos. Isquemia. Traumatismo por reperfusão. FRANCISCHETTI, I ET AL -Leukocytes and the inflammatory response in ischemia-reperfusion injuryRev Bras Cir Cardiovasc 2010; 25(4): 575-584

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“…Proof-of-principle experimental data in animal models indicate that caspase inhibition improves various conditions, including myocardial infarct (Table 1) or stroke-related ischemia/reperfusion injury of the brain, liver and other organs [35][36][37]. This protective effect is at least in part related to the limitation of the inflammatory response by caspase inhibition [38,39].…”

Section: Caspases: Modulators Of Apoptosis and Cytokine Maturationmentioning

confidence: 99%

Anticancer drugs of tomorrow: apoptotic pathways as targets for drug design

Łos

Burek

Stroh

et al. 2003

Drug Discovery Today

111

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Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor

Abstract: ZVAD-fmk was effective in reducing myocardial reperfusion injury, which could at least be partially attributed to the attenuation of cardiomyocyte apoptosis.

Cited by 579 publications

References 14 publications

Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury

Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury

Os leucócitos e a resposta inflamatória na lesão de isquemia-reperfusão

Anticancer drugs of tomorrow: apoptotic pathways as targets for drug design

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