The role of heme metabolism during the induction of hepatic and renal cytochrome P-450 levels and drug-metabolizing enzymes in rats by a Prudhoe Bay crude oil

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Abstract
Administration of Prudhoe Bay crude oil (PBCO) to rats resulted in a dose-related (i) increase in liver weight; (ii) rapid and marked increase in the activity of hepatic δ-aminolevulinate synthetase, the initial and rate-limiting enzyme in the heme biosynthetic pathway; (iii) rapid decline in the activity of hepatic heme oxygenase, the rate-limiting enzyme of heme catabolism; and (iv) more gradual increase in the levels of hepatic cytochrome P-450 and some mixed-function oxidase activities such as benzo[a]pyrene hydroxylase and 7-ethoxyresorufin-O-deethylase. PBCO treatment also increased renal cytochrome P-450 levels and mixed-function oxidase activities; however, δ-aminolevulinate synthetase and heme oxygenase activities were unchanged. This suggests that different regulatory mechanism(s) may be involved in renal heme metabolism and induction of monoxygenase system.