Myocardial cell damage by fatty acid ethyl esters.
Fatty acid ethyl ester (FAEE), a myocardial metabolite of ethanol, causes mitochondrial dysfunction in vitro in rabbits. We investigated the effect of these esters on rat heart mitochondria in vitro and in vivo. In vitro studies were conducted to investigate the binding of ethyl oleate (FAEE) to mitochondria and their capacity to hydrolyze these FAEE. In vivo effects of ethyl esters were studied by the direct transfer of [3H]oleate into the myocardium. Mitochondria were prepared from the myocardium of injected rats, and the amount of [3H]oleate bound to them was determined. In another in vivo study, 50 microliters of 50 microM cold oleic acid ethyl ester was injected into the rat myocardium and the histopathological changes induced by oleic acid ethyl ester were examined by light microscopy. Our results show that fatty acid ethyl ester can bind to myocardial mitochondria in vitro as well as in vivo and the mitochondria can hydrolyze FAEE to fatty acid, which is a known uncoupler of oxidative phosphorylation. Of the total ethyl [3H] oleate injected, 8 microM [3H]oleate and 1 microM ethyl [3H]oleate was bound to the mitochondria. Significant myocardial cell damage was first observed on day 4 and markedly increased on day 30 after ethyl ester injection, with cells showing gross deformation and enlargement. However, no significant histopathological changes were observed in the myocardial tissue on day 2 after injection. Our results suggest that the FAEE may damage the myocardial cells as well as the mitochondria and may provide a metabolic link between ethanol abuse and myocardial dysfunction.
Bora
P S
PS
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri 63110, USA.
Farrar
M A
MA
Miller
D D
DD
Chaitman
B R
BR
Guruge
B L
BL
D000818:Animals; D003451:Cryoprotective Agents / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006868:Hydrolysis; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D009829:Oleic Acids / Q000378:metabolism*; D051381:Rats
D003451:Cryoprotective Agents; D005230:Fatty Acids, Nonesterified; D009829:Oleic Acids; D004121:Dimethyl Sulfoxide; C033180:ethyl oleate