Effect of pyrantel and dimethoate administration on rat liver cytochrome P450 system

The cytochrome P450 system in rat liver after administration of dimethoate (5 d, 1/10 DL50), pyrantel embonate (3 d, 115 DL50) or both xenobiotics simultaneously was analysed. Both compounds were administered directly to the stomach by the tube and the components of cytochrome P450 system were analysed in the microsomal fraction of the liver up to 14 d after the last applied dose. Intoxication with pyrantel diminished the total content of cytochrome P450 in all analysed time intervals. On the other hand, intoxication with dimethoate resulted in increase in the cytochrome P450 content 2 d after the last applied dose. The changes in activities of NADPH: cyt.P450 and NADH: cyt.b(5) reductases were small and statistically not significant. Both dimethoate and pyrantel affected the expression of CYP1A2, CYP2B1/2 and CYP3A1 proteins. Both compounds had a slight negative effect on CYP2B1/2. In animals receiving dimethoate as well as both xenobiotics simultaneously a significant increase in the level of CYP1A2 protein was observed. However, stimulatory effect of dimethoate on the expression of CYP1A2 was abolished by simultaneous intoxication with pyrantel. The changes in CYP3A1 protein expression corresponded with those observed for the total amount of cytochrome P450.