Effects of Sodium Metallochlorophyllins on the Activity and Components of the Microsomal Drug-Metabolizing Enzyme System in Rat Liver

Several sodium metallochlorophyllins (Me-Chl-Na), i.e., sodium copper chlorophyllin (Cu-Chl-Na), sodium cobalt chlorophyllin and sodium iron chlorophyllin, decreased the activities of aminopyrine N-demethylase and aniline hydroxylase and the content of cytochrome P-450 in liver microsomes when given intraperitoneally to rats. The lowest levels of these variables were observed 24h after dosing. Me-Chl-Na administration did not modify the substrate-induced spectral changes of cytochrome P-450. Of the kinetic parameters studied in aminopyrine N-demethylation and aniline hydroxylation, only the Vmax values were markedly decreased by Cu-Chl-Na, indicating that the enzyme inhibition was non-competitive. Me-Chl-Na also reduced cytochrome b5 and total heme contents and NADPH-cytochrome c reductase activity in microsomes. Preincubation of liver microsomes from control rats with Cu-Chl-Na did not cause any reduction in the aminopyrine-and aniline-metabolizing enzyme activities and in the cytochrome P-450 content.These findings strongly suggest that the decreases in the activities of the hepatic microsomal drug-metabolizing enzyme system caused by Me-Chl-Na are correlated with the reduction in the contents of microsomal cytochromes P-450 and b5, and are brought about by primary action(s) of Me-Chl-Na on the control mechanism of microsomal hemoprotein levels, not by direct action of Me-Chl-Na on the system.