Ethanol-induced lipid peroxidation: potentiation by long-term alcohol feeding and attenuation by methionine.
Lipid peroxidation has been incriminated in some types of drug-induced liver injury, but it is unclear whether it contributes to or is present in alcoholic liver injury. In order to study this question, hepatic lipid peroxidation (measured as formation of diene conjugates) and hepatic GSH were assessed in baboons and rats after short- and long-term ethanol administration. Compared to controls, baboons fed alcohol for 1 to 4 years (chronic administration) had increased hepatic diene conjugates (16.9 +/- 4.8 OD/gm of liver) and depressed GSH (3.8 +/- 0.6 VS. 6.3 +/- 0.8 mumol/gm of liver; p less than 0.01) after an overnight withdrawal from ethanol. Administration of 1.6 gm/kg ethanol over 6 hr (acute administration) increased diene conjugates (17.6 +/- 4.3) and decreased GSH (3.2 +/- 0.5; p less than 0.01) in control animals and had an even greater effect in animals chronically fed alcohol (diene conjugates 48.5 +/- 9.2; GSH 1.8 +/- 0.3; p less than 0.001). In six rats fed alcohol for 5 to 6 weeks (chronic administration), an increase in diene conjugates was detected in microsomes (0.343 +/- 0.210 OD/mg of lipid) and mitochondria (0.143 +/- 0.061), accompanied by decrease in arachidonic acid and C22 polyenes, after acute ethanol administration (3 gm/kg p.o.) but no significant change in GSH. Simultaneous administration of methionine attenuated diene conjugate formation (0.107 +/- 0.058 and 0.035 +/- 0.020 OD/mg of lipid, respectively) and fatty acid changes. Thus chronic alcohol feeding potentiates lipid peroxidation produced by an acute dose of ethanol; these changes are not dependent on GSH depression but may be potentiated by it.
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000032:analysis / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D010215:Papio; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D013997:Time Factors
D005227:Fatty Acids; D008054:Lipid Peroxides; D010743:Phospholipids; D000431:Ethanol; D008715:Methionine; D005978:Glutathione