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Role of Acetaldehyde and Acetate in the Development of Ethanol‐Induced Cardiac Lipidosis, Studied in Isolated Perfused Rat Hearts
Author(s) -
Kiviluoma Kai,
Hassinen Ilmo
Publication year - 1983
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1983.tb05433.x
Subject(s) - acetaldehyde , ethanol , nad+ kinase , chemistry , redox , biochemistry , metabolism , ethanol metabolism , organic chemistry , enzyme
Isolated perfused rat hearts were used to study the effects of ethanol, acetaldehyde, and acetate on the cellular redox state and tatty 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 μm 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 μm, 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 rnillimolar concentrations caused an extensive reduction of mitochondrial NAD + and an increase in the coronary flow. A mitochondrial acetaldehyde dehydrogenaae was revealed in the myocardium, having an apparent K, of 1.l μm for acetaldehyde. Acetaldehyde in 50μm 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 its oxidation and enhance its incorporation into tissue lipids in a dosedependent 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 signlficant 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.