Polyenylphosphatidylcholine opposes the increase of cytochrome P-4502E1 by ethanol and corrects its iron-induced decrease.
Dietary iron overload damages membrane phospholipids and decreases microsomal cytochromes P-450. We wondered whether this might also pertain to cytochrome P-4502E1 (2E1) and whether polyenylphosphatidylcholine (PPC), a 94-96% pure mixture of linoleate-rich polyunsaturated phosphatidylcholines that protects against alcohol-induced liver injury, also affects 2E1, either in the presence or absence of iron. Accordingly, rats were fed for 8 weeks our standard liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either PPC (3 g/1000 Cal) or equivalent amounts of linoleate (as safflower oil). 2E1 was assessed by Western blots and by two of its characteristic enzyme activities: the microsomal ethanol oxidizing system (MEOS), evaluated by the conversion of ethanol to acetaldehyde (determined by head space GC), and p-nitrophenolhydroxylase (PNP) activity, measured by HPLC with UV detection of 4-nitrocatechol. With ethanol (36% of energy) replacing carbohydrates, 2E1 content increased 10-fold, with a corresponding increase in PNP and MEOS activities, but when carbonyl iron (5 g/1000 Cal) was added, the induction was significantly reduced. This iron-induced decrease was corrected by PPC. PPC is rich in linoleate, but when the latter was given as triglycerides (safflower oil), there was no effect, whereas hepatic nonheme iron content was the same in both these groups. It also was found that in the absence of iron, the ethanol-mediated induction of 2E1 and its corresponding enzyme activities were significantly less with PPC (< 0.001) than with safflower oil. In addition, in alcohol-fed animals, PPC decreased the oxidative stress (as determined by F2-isoprostanes), which reflects yet another hepatoprotective effect of PPC.
Aleynik
M K
MK
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center and Mount Sinai School of Medicine, New York 10468, USA.
Leo
M A
MA
Aleynik
S I
SI
Lieber
C S
CS
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects* / Q000378:metabolism; D004042:Dietary Fats, Unsaturated; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010713:Phosphatidylcholines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D004042:Dietary Fats, Unsaturated; D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; C005152:lipostabil; D000431:Ethanol; D007501:Iron; D019392:Cytochrome P-450 CYP2E1