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Xenobiotica
the fate of foreign compounds in biological systems
Volume 26, 1996 - Issue 11
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Original Article

Gender differences in ethanol oxidation and cytochrome P4502E1 content and functions in hepatic microsomes from alcohol-preferring and non-preferring rats

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Pages 1121-1129 | Received 30 Apr 1996, Published online: 27 Aug 2009
 

Abstract

1. We have studied the hepatic microsomal metabolism of ethanol (MEOS), CYP2E1 expression and catalytic activity, and the response to phenobarbital (PB) induction or CCl4 challenge in rats of either sex genetically selected for their preference (P) or aversion (NP) for ethanol.

2. In Pversus NP females, the amount of both total cytochrome P450 and P450 binding to metyrapone was lower, whereas the activities of MEOS, aniline 4-hydroxylase (4-AOH), and 4-nitrophenol hydroxylase (PNP-OH) as well as the level of immunodetectable CYP2E1 content were consistently higher. By contrast, no substantial differences were observed between P and NP males.

3. Despite an apparent down-regulation of CYP2E1 expression occurring in all rats as a result of PB induction, P females maintained higher 2E1 levels and showed enhanced MEOS, 4-AOH and PNP-OH activities with respect to NP females. No such changes were detected in the male counterparts.

4. No sex-related differences in CCl4-mediated inhibition of monooxygenase or MEOS activities were evident between P and NP animals.

5. These results indicate that, in females only, the behavioural trait of ethanol preference is apparently associated not only with higher constitutive levels of CYP2E1 and rate of microsomal metabolism of ethanol but also with altered susceptibility to PB induction.

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