ZINC ETHYLENE-BIS-DITHIOCARBAMATE (ZINEB)-MEDIATED INHIBITION OF MONOOXYGENASES AND LIPID-PEROXIDATION IN BOVINE LIVER-MICROSOMES

Hepatic bovine microsomes were incubated with Zineb concentrations ran ging from 2.5 mM to 2.5 mu M. Only the higher concentrations of the fu ngicide (2.5 and 0.25 mM) elicited a sharp decline in cytochrome P450, cytochrome b(5) and total sulphydryl groups content as well as in the activities of NADPH cytochrome c reductase, aminopyrine N-demethylase and aniline 4-hydroxylase. The loss of cytochrome P450 was matched by a concomitant increase in the amount of cytochrome P420, which repres ents a catalytically inactive form of cytochrome P450. The same concen trations of the fungicide. either alone or in the presence of NADPH 1 mM, failed to increase the amount of thiobarbituric reactive substance s with respect to control incubations, thereby excluding the possibili ty of lipid peroxidation as a contributing factor in the loss of cytoc hrome P450 and in the inhibition of cytochrome P450-mediated metabolis m. It is concluded that Zineb can depress monooxygenase activity in bo vine hepatic microsomes mainly through the denaturation of cytochrome P450 and the impaired transfer of reducing equivalents to the complex cytochrome P450-substrate. These mechanisms might also account for the inhibition in lipid peroxidation brought about by the fungicide.