Polyenylphosphatidylcholine opposes the increase of cytochrome P-4502E1 byethanol and corrects its iron-induced decrease

Dietary iron overload damages membrane phospholipids and decreases microsom al cytochromes P-450, We wondered whether this might also pertain to cytoch rome P-45ME1 (2E1) and whether polyenylphosphatidylcholine (PPC), a 94-96% pure mixture of linoleate-rich polyunsaturated phosphatidylcholines that pr otects against alcohol-induced liver injury, also affects 2E1, either in th e presence or absence of iron. Accordingly, rats were fed for 8 weeks our s tandard liquid diet containing ethanol (36% of energy) or isocaloric carboh ydrates, with either PPC (3 g/1000 Gal) or equivalent amounts of linoleate las safflower oil). 2E1 was assessed by Western blots and by two of its cha racteristic enzyme activities: the microsomal ethanol oxidizing system (MEO S], evaluated by the conversion of ethanol to acetaldehyde (determined by h ead space GC), and p-nitrophenolhydroxylase (PNP) activity, measured by HPL C with UV detection of 4-nitrocatechol. With ethanol (36% of energy] replac ing carbohydrates, 2E1 content increased 10-fold, with a corresponding incr ease in PNP and MEOS activities, but when carbonyl iron (5 g/1000 Gal) 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 giv en as triglycerides (safflower oil), there was no effect, whereas hepatic n onheme iron content was the same in both these groups, It also was found th at in the absence of iron, the ethanol-mediated induction of 2E1 and its co rresponding enzyme activities were significantly less with PPC (p < 0.001) than with safflower oil, In addition, in alcohol-fed animals, PPC decreased the oxidative stress las determined by F-2-isoprostanes), which reflects y et another hepatoprotective effect of PPC.