Monohydroperoxidized fatty acids but not 4-hydroxynonenal induced acute cardiac cell damage.
Unsaturated fatty acids constitutive of cardiac membranal lipid matrix are one of the primary targets for reactive oxygen species generated during ischemia-reperfusion cycle. Lipid peroxidation is a cascade of intricate reactions involving the successive formations of fatty acids hydroperoxides and aldehydic compounds such as alkenals derived from the oxidative fragmentation of these hydroperoxides. The potential deleterious effects of different classes of lipid peroxidation products on cardiac cells were compared using three in vitro approaches: (i) cardiomyocyte integrity, (ii) electromechanical activity of papillary muscle, and (iii) atrial contractility. The following products of lipid peroxidation were tested: (i) photoperoxidized arachidonic acid pooling hydroperoxidized derivatives and aldehydic compounds, (ii) fatty acids hydroperoxides, and (iii) 4-hydroxynonenal, a characteristic alkenal derived from the oxidative fragmentation of hydroperoxidized n-6 fatty acids. Only fatty acids hydroperoxides induced drastic loss of cellular integrity and severe disturbances in electromechanical activity of cardiomyocytes. 4-hydroxynonenal induced only a slight leak of lactate dehydrogenase at high concentrations and did not modify the electromechanical behavior of cardiac preparations. Under our conditions, monohydroperoxidized fatty acids but not 4-hydroxynonenal induced acute cardiac cell damages. In conclusion, lipid hydroperoxides can be considered both as markers of oxidative injury and relay sources of oxidative stress.
Iliou
J P
JP
Division Pathologies Cardiaques et Vasculaires, Institut de Recherches Servier, Suresnes, France.
Thollon
C
C
Villeneuve
N
N
Robin
F
F
Cambarrat
C
C
Jacquemin
C
C
Vilaine
J P
JP
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D016275:Atrial Function; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D004594:Electrophysiology; D005227:Fatty Acids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D015289:Leukotrienes / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000502:physiology; D010777:Photochemistry; D051381:Rats; D017208:Rats, Wistar; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D000447:Aldehydes; D005227:Fatty Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D006861:Hydrogen Peroxide; C027576:4-hydroxy-2-nonenal