Polyenylphosphatidylcholine corrects the alcohol-induced hepatic oxidative stress by restoring s-adenosylmethionine.
OBJECTIVE
Since the late stages of alcoholic liver injury are associated with decreased activity of methionine adenosyltransferase (MAT), we wondered whether this already occurs at the early stages and what is the mechanism involved.


METHODS
Sprague-Dawley rats (n = 32) were pair-fed ethanol (36% of energy) or isocaloric carbohydrates (control) in Lieber-DeCarli liquid diets, with or without polyenylphosphatidylcholine (PPC).


RESULTS
After 2 months, there was a striking depletion of S-adenosylmethionine (measured by high-performance liquid chromatography) from 68.2 +/- 5.1 to 36.2 +/- 3.4 nmol/g, associated with a reduction in hepatic reduced glutathione (GSH) from 4.95 +/- 0.20 to 4.09 +/- 0.08 micro mol/g, and an increase from 0.24 +/- 0.02 to 0.47 +/- 0.07 nmol/g of 4-hydroxynonenal (4-HNE), a reliable marker of lipid peroxidation. Hepatic S-adenosylmethionine (SAMe) correlated positively with GSH (r = 0.5916) and negatively with 4-HNE (r = -0.6375). Feeding PPC corrected all values and MAT activity did not differ significantly between groups.


CONCLUSIONS
SAMe depletion occurs already after 8 weeks of alcohol feeding and is fully corrected by PPC, in parallel with the prevention by PPC of the alcohol-induced oxidative stress. Since phosphatidylcholines (PCs) are produced in the liver via methylation of phosphatidylethanolamine by SAMe, it is likely that PPC, by providing PCs, decreases the utilization of SAMe and thereby contributes to its restoration, with replenishment of GSH and correction of the alcohol-induced oxidative stress.
Aleynik
Semyon I
SI
Alcohol Research Center, Section of Liver Disease and Nutrition, Bronx VA Medical Center and Mount Sinai School of Medicine, New York, NY, USA.
Lieber
Charles S
CS
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005235:Fatty Liver, Alcoholic / Q000378:metabolism* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000378:metabolism*
D010713:Phosphatidylcholines; C005152:lipostabil; D012436:S-Adenosylmethionine