An induction of heme oxygenase and its possible relation to the decrease of cytochrome P-450 content during liver regeneration.

Abstract

The alterations of various enzymes responsible for drug metabolism and heme metabolism were examined in regenerating livers of male rats. Microsomal cytochrome P-450 content and aminopyrine demethylase activity were significantly decreased during liver regeneration. In contrast, microsomal heme oxygenase activity was markedly increased under the identical conditions. The increased heme oxygenase activity which appeared within 4 h and reached maximum at 1 d after partial hepatectomy was sustained for 5 d. In sham-operated rats, the changed patterns of these parameters were similar, but to a lesser extent as compared to partially hepatectomized rats. The increase of heme oxygenase activity following partial hepatectomy was blocked by the administration of cycloheximide or actinomycin D. Other enzymes involved in heme synthesis did not change appreciably during liver regeneration. The inverse relationship between the decrease of cytochrome P-450 content and the increase of heme oxygenase activity was also observed in female rats and male mice. These findings suggest that the increase of heme oxygenase activity in regenerating rodent liver would be correlated to the decrease of cytochrome P-450 content. Adrenalectomy enhanced the increase of heme oxygenase activity following partial hepatectomy, though the decrease of cytochrome P-450 content was less extensive under the experimental conditions. The results also suggest that the inverse relationship between the increase of heme oxygenase activity and the decrease of cytochrome P-450 content would be a biochemical phenomenon seen in regenerating liver and that the phenomenon would not be simply due to the surgical stress to the animals.