The effect of phenobarbital, 3-methylcholanthrene, 3,4-benzpyrene, and pregnenolone-16α-carbonitrile on microsomal heme oxygenase and splenic cytochrome P-450

Abstract

Inducers of the microsomal electron transport system (cytochrome P-450 and NADPH-cytochrome P-450 reductase), including phenobarbital, 3-methylcholanthrene, 3,4-benzpyrene, and pregnenolone-16α-carbonitrile, were tested for their effects on hepatic and splenic heme oxygenase activity and splenic cytochrome P-450 content in male Holtzman rats. Phenobarbital treatment caused no induction of heme oxygenase or splenic cytochrome P-450. 3-Methylcholanthrene administration produced a significant decrease in hepatic and splenic heme oxygenase activity but with no discernible change in splenic cytochrome P-450. 3,4-Benzpyrene treatment caused a decrease in splenic heme oxygenase specific activity, no change in hepatic heme oxygenase, and in only one experiment marked induction of splenic cytochrome P-450. Pregnenolone-16α-carbonitrile caused slight but variable decreases in hepatic and splenic heme oxygenase activity but was the most potent inducer of splenic cytochrome P-450 tested. These results suggest that although the elements of the microsomal electron transport system are involved in oxidative heme catabolism in liver and spleen, the process is regulated in a unique manner as compared with the metabolism of other xenobiotics and polycyclic hydrocarbons.