In vitro inhibitory action of cadmium on microsomal monooxygenases of rabbit lung

Abstract

In vitro addition of cadmium (Cd) salts to pulmonary microsomes isolated from male rabbits decreased the cytochrome P-450 levels and the activity of benzo[ a]pyrene hydroxylase and aminopyrine N-demethylase but not that of NADPH-cytochrome c reductase. The Cd-induced reduction of pulmonary monooxygenase activity was enhanced when microsomes were preincubated in the presence of Cd and inhibition increased as the time of preincubation progressed, attaining its maximum rate at 20 min of preincubation. When hepatic microsomes were used, this delayed effect of Cd on monooxygenase was less apparent. The presence of NADH and/or NADPH in the preincubation did not markedly enhance the Cd-induced inhibition rate of monooxygenase activity. The addition of Cd-acetate to pulmonary microsomes produced a concentration-dependent inhibition of the monooxygenase activity and the estimated IC 50 values of Cd-acetate (i.e. the concentration required to inhibit control enzyme activity by 50%) were 3.8 × 10 −5 M, 6.5 × 10 −6 M and 5.3 × 10 −5 M for cytochrome P-450, benzo[ a]pyrene hydroxylase and aminopyrine N-demethylase, respectively. The inhibitory action of Cd-acetate on the monooxygenase activity was also observed with microsomes isolated from the lungs of male guinea-pigs and rats.