Comparison of nitrosocarbaryl and carbaryl: in vitro effects on hepatic microsomal aryl hydrocarbon hydroxylase, aminopyrine N-demethylase, epoxide hydrolase and cytosolic glutathione-S-transferase.

The Comparative effects of nitrosocarbaryl and carbaryl on rat hepatic microsomal aryl hydrocarbon hydroxylase, aminopyrine-N-demethylase, epoxide hydrolase and cytosolic glutathione-S-transferase in vitro was investigated. The effects of nitrosocarbaryl on these hepatic drug metabolizing enzyme systems differ markedly (P less than 0.05) from carbaryl. Nitrosocarbaryl was more potent and had much higher inhibitory effect than carbaryl on microsomal aryl hydrocarbon hydroxylase, aminopyrine N-demethylase, epoxide hydrolase and cytosolic glutathione-S-transferase. Inhibition of these enzyme systems by nitrosocarbaryl was dose-dependent. In microsomes, nitrosocarbaryl showed a significant (P less than 0.001) inhibition of aryl hydrocarbon hydroxylase and aminopyrine N-demethylase as compared with the control when the concentration of nitrosocarbaryl added was above 1 X 10(-5) M. The I50 values were 1.8 X 10(-5) M and 3.5 X 10(-5) M, respectively. Nitrosocarbaryl inhibited epoxide hydrolase activity gradually up to 18% at the range of concentration studied (1.3 X 10(-3) M - 1.2 X 10(-2) M) and showed a significant (P less than 0.001) inhibition at the concentration of 1.2 X 10(-2) M. Nitrosocarbaryl at concentrations above 1.6 X 10(-4) M showed a significant (P less than 0.001) inhibition of cytosolic glutathione-S-transferase activity with an I50 value of 3.8 X 10(-4) M. By Contrast, carbaryl failed to inhibit aryl hydrocarbon hydroxylase at concentrations below 3 X 10(-4) M. The pesticide inhibited the enzyme activity only by 20% at the maximum concentration studied (6 X 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)