Role of acetaldehyde and acetate in the development of ethanol-induced cardiac lipidosis, studied in isolated perfused rat hearts.
Isolated perfused rat hearts were used to study the effects of ethanol, acetaldehyde, and acetate on the cellular redox state and fatty acid metabolism in the myocardium. Ethanol had negligible effects on the cellular redox state but at high concentrations depressed the contractile activity and thereby secondarily the oxygen consumption. Acetaldehyde in concentrations below 50 microM had negligible effects on the redox state of the mitochondrial free NAD+/NADH couple, as studied by surface fluorometry of flavins and nicotinamide nucleotides. A reduction of NAD+ was observed with concentrations between 50 and 500 microM, while in the range of 0.5-1 mM the effect was biphasic, i.e., an initial reduction was followed by oxidation concomitantly with an increase in heart rate and peak systolic pressure. Acetate in millimolar concentrations caused in the coronary flow. A mitochondrial acetaldehyde dehydrogenase was revealed in the myocardium, having an apparent Km of 1.1 microM for acetaldehyde. Acetaldehyde in 50-microM concentration had no major effects on the uptake, oxidation, or lipid incorporation of oleate in the myocardium. Acetate in concentrations less than 2 mM did not affect the uptake of oleate into the myocardium, but did inhibit is oxidation and enhance its incorporation into tissue lipids in a dose-dependent manner. 2 mM acetate caused a 91% increase in oleate incorporation into tissue lipids over 30 min. The data can be interpreted as showing that acetaldehyde and acetate, the metabolites of ethanol, have metabolic effects on the myocardium, but only those of acetate are significant in concentrations encountered during ethanol oxidation in vivo. It is probable that acetate is involved in the development of ethanol-induced myocardial lipidosis, inhibiting the oxidation of fatty acids, and channelling them into the esterification pathway.
D000079:Acetaldehyde / Q000378:metabolism*; D000085:Acetates / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism*; D005260:Female; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D009829:Oleic Acids; D019301:Oleic Acid; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde