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 del eterious effects of different classes of lipid peroxidation products o n cardiac cells were compared using three in vitro approaches: (i) car diomyocyte integrity, (ii) electromechanical activity of papillary mus cle, and (iii) atrial contractility. The following products of lipid p eroxidation were tested: (i) photoperoxidized arachidonic acid pooling hydroperoxidized derivatives and aldehydic compounds, (ii) fatty acid s hydroperoxides, and (iii) 4-hydroxynonenal, a characteristic alkenal derived from the oxidative fragmentation of hydroperoxidized n-6 fatt y acids. Only fatty acids hydroperoxides induced drastic loss of cellu lar integrity and severe disturbances in electromechanical activity of cardiomyocytes. 4-hydroxynonenal induced only a slight leak of lactat e dehydrogenase at high concentrations and did not modify the electrom echanical behavior of cardiac preparations. Under our conditions, mono hydroperoxidized fatty acids but not 4-hydroxynonenal induced acute ca rdiac cell damages. In conclusion, lipid hydroperoxides can be conside red both as markers of oxidative injury and relay sources of oxidative stress.