Nature of the cardiomyocyte injury induced by lipid hydroperoxides
Cardiovascular Research
C ThollonJ P Vilaine
Abstract
As a result of oxidative stress to membrane lipid matrix, the peroxidation of polyunsaturated fatty acids induced the transient formation of lipid hydroperoxides (ROOH). The aim of this study was to evaluate the damaging effects of ROOH on the cardiac cell and the link between the alterations observed and intracellular calcium overload. Necrosis of cultured rat cardiac cells was determined by measuring the release of lactate dehydrogenase (LDH). In guinea-pig papillary muscles, action potential (AP) and isometric tension were recorded with standard microelectrodes and a transducer, respectively. The reactive oxygen species (ROS) scavenging properties of tested compounds were determined using a cell-free model of lipid photoperoxidation. 15(S)-HpETE (15(S)-hydroperoxyeicosatetraenoic acid), an arachidonic acid hydroperoxide, induced a concentration-dependent loss of cardiomyocytes membrane integrity. The release of LDH induced by 15(s)-HpETE (30 microM) was prevented by a ROS scavenger, BW755C (10 microM), but not by a sarcolemmal calcium channel blocker, Amlodipine (10 microM), or a calcium overload protective agent, R56865 (10 microM). Cardiomyocytes necrosis induced by calcium paradox was prevented by Amlodipine (10 microM) a...Continue Reading