EFFECTS OF ISONIAZID TREATMENT ON SELECTED HEPATIC MIXED-FUNCTION OXIDASES

Abstract

The hepatic microsomal content of cytochromes P-450 and b5, the defluorination rates of 4 volatile fluorinated ether anesthetics and the activities of selected mixed-function oxidases were compared after administration of isoniazid, phenobarbital, .beta.-naphthoflavone or saline to male Fischer 344 rats. Isoniazid treatment significantly increased the rate of metabolism of p-nitroanisole, ethoxyresorufin, aniline, methoxyflurane, enflurane, isoflurane and sevoflurane, significantly decreased the rate of metabolism of aminopyrine and did not alter the activity of NADPH-cytochrome c reductase or the microsomal contents of cytochromes b5 and P-450/mg of microsomal protein. The pattern of catalytic activities associated with isoniazid induction did not resemble that phenobarbital or .beta.-naphthoflavone induction. Isoniazid treatment caused a shift in the (reduced cytochrome P-450 plus CO) absorption maximum from 450-451 nm. This shift in absorption, coupled with the observation that the total microsomal cytochrome P-450 content is not elevated, suggests that there is an increased production of 1 sp. of cytochrome P-450. The great enhancement of enflurane defluorination after isoniazid treatment was interesting because other enzyme inducing agents, including phenobarbital, 3-methylcholanthrene, phenytoin and .beta.-naphthoflavone, do not increase enflurane defluorination to a clinically significant level.