Dilinoleoylphosphatidylcholine decreases ethanol-induced cytochrome P4502E1.
Cytochrome P4502E1 (CYP2E1) induction by ethanol contributes to alcoholic liver disease and we found that a mixture of polyunsaturated phosphatidylcholines (PPC), which protects against alcohol-induced liver injury, also decreases CYP2E1. Since dilinoleoylphosphatidylcholine (DLPC) is the major component of PPC, we assessed here whether it is responsible for the protection of PPC by feeding rats for 8 weeks our liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either DLPC (1.5 g/1000 cal), PPC (3 g/1000 cal), or linoleate. CYP2E1 was assessed by Western blots and by two of its enzyme activities: the microsomal ethanol-oxidizing system (MEOS) and p-nitrophenolhydroxylase (PNP). With ethanol, CYP2E1 increased 10-fold, with corresponding rises in PNP and MEOS activities. Compared to linoleate, DLPC significantly decreased cytochrome b(5), total cytochromes P450, CYP2E1 content and its corresponding activities. DLPC decreases ethanol-induced CYP2E1 and should be considered for the prevention of alcoholic liver disease.
Aleynik
M K
MK
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center and Mount Sinai School of Medicine, Bronx, New York 10468, USA.
Lieber
C S
CS
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D015786:Cytochromes b5 / Q000032:analysis / Q000378:metabolism; D004032:Diet; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D010713:Phosphatidylcholines; C029449:polyene phosphatidylcholine; D000431:Ethanol; C002448:1,2-linoleoylphosphatidylcholine; D015786:Cytochromes b5; D019787:Linoleic Acid; D019392:Cytochrome P-450 CYP2E1