Non-enzymatic oxidized metabolite of DHA, 4( RS )-4-F 4t -neuroprostane protects the heart against reperfusion injury - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Free Radical Biology and Medicine Année : 2017

Non-enzymatic oxidized metabolite of DHA, 4( RS )-4-F 4t -neuroprostane protects the heart against reperfusion injury

Patrice Bideaux
Jetty Chung-Yung Lee

Résumé

Acute myocardial infarction leads to an increase in oxidative stress and lipid peroxidation. 4(RS)-4-F4t-Neuroprostane (4-F4t-NeuroP) is a mediator produced by non-enzymatic free radical peroxidation of thecardioprotective polyunsaturated fatty acid, docosahexaenoic acid (DHA). In this study, we investigated whetherintra-cardiac delivery of 4-F4t-NeuroP (0.03 mg/kg) prior to occlusion (ischemia) prevents and protects ratmyocardium from reperfusion damages.Using a rat model of ischemic-reperfusion (I/R), we showed that intra-cardiac infusion of 4-F4t-NeuroPsignificantly decreased infarct size following reperfusion (−27%) and also reduced ventricular arrhythmia scoreconsiderably during reperfusion (−41%). Most notably, 4-F4t-NeuroP decreased ventricular tachycardia andpost-reperfusion lengthening of QT interval. The evaluation of the mitochondrial homeostasis indicates alimitation of mitochondrial swelling in response to Ca2+by decreasing the mitochondrial permeability transitionpore opening and increasing mitochondria membrane potential. On the other hand, mitochondrial respirationmeasured by oxygraphy, and mitochondrial ROS production measured with MitoSox red®were unchanged. Wefound decreased cytochrome c release and caspase 3 activity, indicating that 4-F4t-NeuroP prevented reperfusiondamages and reduced apoptosis. In conclusion, 4-F4t-NeuroP derived from DHA was able to protect I/R cardiacinjuries by regulating the mitochondrial homeostasis
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Dates et versions

hal-01822214 , version 1 (20-12-2019)

Identifiants

Citer

Jérôme Roy, J. Fauconnier, Camille Oger, Charlotte Farah, Claire Angebault, et al.. Non-enzymatic oxidized metabolite of DHA, 4( RS )-4-F 4t -neuroprostane protects the heart against reperfusion injury. Free Radical Biology and Medicine, 2017, 102, pp.229 - 239. ⟨10.1016/j.freeradbiomed.2016.12.005⟩. ⟨hal-01822214⟩
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