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Pasdois 2008 Am J Physiol Heart Circ Physiol

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Pasdois P, Beauvoit B, Tariosse L, Vinassa B, Bonoron-Adรจle S, Dos Santos P (2008) Effect of diazoxide on flavoprotein oxidation and reactive oxygen species generation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers. Am J Physiol Heart Circ Physiol 294:H2088-97.

ยป PMID: 18296562 Open Access

Pasdois Philippe, Beauvoit Bertrand, Tariosse Liliane, Vinassa Beatrice, Bonoron-Adele Simone, Santos Pierre (2008) Am J Physiol Heart Circ Physiol

Abstract: This study analyzed the oxidant generation during ischemia-reperfusion protocols of Langendorff-perfused rat hearts, preconditioned with a mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) opener (i.e., diazoxide). The autofluorescence of mitochondrial flavoproteins, and that of the total NAD(P)H pool on the one hand and the fluorescence of dyes sensitive to H2O2 or O2*- [i.e., the dihydrodichlorofluoroscein (H2DCF) and dihydroethidine (DHE), respectively] on the other, were noninvasively measured at the surface of the left ventricular wall by means of optic fibers. Isolated perfused rat hearts were subjected to an ischemia-reperfusion protocol. Opening mitoK(ATP) with diazoxide (100 microM) 1) improved the recovery of the rate-pressure product after reperfusion (72 +/- 2 vs. 16.8 +/- 2.5% of baseline value in control group, P < 0.01), and 2) attenuated the oxidant generation during both ischemic (-46 +/- 5% H2DCF oxidation and -40 +/- 3% DHE oxidation vs. control group, P < 0.01) and reperfusion (-26 +/- 2% H2DCF oxidation and -23 +/- 2% DHE oxidation vs. control group, P < 0.01) periods. All of these effects were abolished by coperfusion of 5-hydroxydecanoic acid (500 microM), a mitoK(ATP) blocker. During the preconditioning phase, diazoxide induced a transient, reversible, and 5-hydroxydecanoic acid-sensitive flavoprotein and H2DCF (but not DHE) oxidation. In conclusion, the diazoxide-mediated cardioprotection is supported by a moderate H2O2 production during the preconditioning phase and a strong decrease in oxidant generation during the subsequent ischemic and reperfusion phases.

โ€ข Bioblast editor: Plangger M โ€ข O2k-Network Lab: FR Pessac Pasdois P


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Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart 




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