Effects of isoniazid treatment on selected hepatic mixed-function oxidases

The hepatic microsomal content of cytochromes P-450 and b5, the defluorination rates of four volatile fluorinated ether anesthetics, and the activities of selected mixed-function oxidases were compared following administration of either 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 per mg of microsomal protein. The pattern of catalytic activities associated with isoniazid induction did not resemble that of either phenobarbital or beta-naphthoflavone induction. Furthermore, isoniazid treatment resulted in a shift in the (reduced cytochrome P-450 plus CO) absorption maximum from 450 to 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 one species of cytochrome P-450. The great enhancement of enflurane defluorination following isoniazid treatment was of particular interest because other enzyme-inducing agents, including phenobarbital, 3-methylcholanthrene, phenytoin, and beta-naphthoflavone, have not been found to increase enflurane defluorination to a clinically significant level.