INDUCTION OF HEPATIC ARYL-HYDROCARBON HYDROXYLASE AND EPOXIDE HYDRASE IN WISTAR RATS PRETREATED WITH ORAL METHADONE HYDROCHLORIDE

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (2) , 211-218
Abstract
Methadone.cntdot.HCl added to the drinking water of adult female Wistar rats for 4 wk increased aryl hydrocarbon hydroxylase activity of the hepatic microsomal fraction to 222% of control levels. No change was seen in epoxide hydrase activty. When male rats were treated similarly, epoxide hydrase activity increased to 212% of controls with no change in aryl hydrocarbon hydroxylase activity. No such changes were observed when the s.c. administration or chronic, low-dose, i.p. injections were used. There were no differences in hepatic cytochrome P-450 or protein concentrations in treated animals as compared to their respective control groups. Control studies were carried out with quinine sulfate in the drinking water to decrease water intake to the level of the methadone-treated group. No elevation in either enzyme activity occurred. Similarly, paired-feeding studies showed that enzyme activity elevation was due to methadone, not food deprivation. The effects of concurrent therapy of methadone with phenobarbital sodium or 3-methylcholanthrene were compared.