The effect of the prostaglandin analogue-misoprostol on rat liver mitochondria after chronic alcohol feeding.
Rats fed ethanol (36% of total calories in a nutritionally adequate liquid diet) for 5 weeks develop functional alterations of hepatic mitochondria and steatosis of the liver. At the fatty liver stage, ADP-stimulated respiration of mitochondria was depressed in ethanol fed rats by 30% (p less than 0.001) with glutamate + malate and by 23% (p less than 0.001) with succinate as substrates. A similar decrease was noted in the respiratory control ratio (RCR) (34% and 29%, respectively). The total lipid content of the liver increased 2.6 fold (p less than 0.001). Mitochondrial dysfunction could be prevented, in part, by the treatment with a synthetic derivative of prostaglandin E1, misoprostol, at a mean daily dose of 80 micrograms/kg of body weight. The RCR with glutamate + malate as substrates was improved by 36% (p less than 0.05). We conclude that misoprostol attenuates several functional alterations in liver mitochondria during alcohol feeding.
Dlugosz
J W
JW
Alcohol Research and Treatment Center, Bronx VA Medical Center, NY 10468.
Korsten
M A
MA
Lieber
C S
CS
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D005235:Fatty Liver, Alcoholic / Q000378:metabolism / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D016595:Misoprostol; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013385:Succinate Dehydrogenase / Q000378:metabolism
D016595:Misoprostol; D013385:Succinate Dehydrogenase; D001219:Aspartate Aminotransferases; D000527:Alprostadil