P-450-dependent metabolism of lauric acid in alcoholic liver disease: comparison between rat liver and kidney microsomes.
作者： Yolande Amet , Daniele Lucas , Zhi-Qi Zhang-Gouillon , Samuel W. French
DOI: 10.1111/J.1530-0277.1998.TB03673.X
关键词:
摘要: Monooxygenase enzymatic activities were measured in liver and kidney microsomes of control ethanol-treated rats. Animals administered alcohol by using a model for alcoholic injury. Several vitro approaches used to compare the laurate metabolism microsomes: correlation studies between specific P-450 catalytic activities, immunoblot analysis, chemical immunoinhibitions. Ethanol treatment increased renal hydroxylations chlorzoxazone 4-nitrophenol. Moreover, lauric acid (ω-1)-hydroxylation was found be significantly (∼6-fold) after ethanol liver, but not microsomes. The ω-1/ω ratio from 1.52 ± 0.49 4.11 1.01 rats, 0.29 0.06 0.44 < 0.07 Immunoblot analysis polyclonal anti-cytochrome (CYP) 2E1 or CYP4A antibodies showed an increase CYP2E1 contents both organs, higher than Chemical inhibitions competitive inhibitors (such as ethanol) led nonsignificant inhibition acid. In contrast, 17-octadecynoic (a mechanism-based inhibitor ω-hydroxylase) able inhibit ω- (ω-1)-hydroxylations Immunoinhibitions decreased microsomes, whereas anti-CYP4A1 antibody inhibited All these results show that respond different manners treatment. Lauric (ω-1)-hydroxylation, highly probe rat human is mediated isoform
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