Roy 2016 Free Radic Biol Med
|Roy J, Fauconnier J, Oger C, Farah C, Angebault-Prouteau C, Thireau J, Bideaux P, Scheuermann V, Bultel-Poncé V, Demion M, Galano JM, Durand T, Lee JC, Le Guennec JY (2016) Non-enzymatic oxidized metabolite of DHA, 4(RS)-4-F4t-neuroprostane protects the heart against reperfusion injury. Free Radic Biol Med 102:229-39.|
Abstract: 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 the cardioprotective polyunsaturated fatty acid, docosahexaenoic acid (DHA). In this study, we investigated whether intra-cardiac delivery of 4-F4t-NeuroP (0.03mg/kg) prior to occlusion (ischemia) prevents and protects rat myocardium from reperfusion damages. Using a rat model of ischemic-reperfusion (I/R), we showed that intra-cardiac infusion of 4-F4t-NeuroP significantly decreased infarct size following reperfusion (-27%) and also reduced ventricular arrhythmia score considerably during reperfusion (-41%). Most notably, 4-F4t-NeuroP decreased ventricular tachycardia and post-reperfusion lengthening of QT interval. The evaluation of the mitochondrial homeostasis indicates a limitation of mitochondrial swelling in response to Ca2+ by decreasing the mitochondrial permeability transition pore opening and increasing mitochondria membrane potential. On the other hand, mitochondrial respiration measured by oxygraphy, and mitochondrial ROS production measured with MitoSox red® were unchanged. We found decreased cytochrome c release and caspase 3 activity, indicating that 4-F4t-NeuroP prevented reperfusion damages and reduced apoptosis. In conclusion, 4-F4t-NeuroP derived from DHA was able to protect I/R cardiac injuries by regulating the mitochondrial homeostasis.
Copyright © 2016 Elsevier Inc. All rights reserved. • Keywords: Ischemia/reperfusion, n-3 polyunsaturated fatty acids, Neuroprostanes, Cardioprotection, Mitochondria, mPTP
• O2k-Network Lab: FR Montpellier Fauconnier J
Labels: MiParea: Respiration Pathology: Cardiovascular Stress:Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS Organism: Rat Tissue;cell: Heart Preparation: Permeabilized cells
Regulation: Calcium Coupling state: OXPHOS, ET Pathway: N, S, NS HRR: Oxygraph-2k