Effect of ivermectin on induction of cytochromes P450 in male rats

Effects of the widely used antiparasitic drug ivermectin on cytochromes P45 0 were tested in adult male rats. Liver microsomes were prepared from anima ls after single or repeated treatments with various doses of ivermectin. Th e hepatic microsomal protein content and activities of cytochromes P450 tow ards alkoxyresorufins and testosterone as the specific substrate probes wer e measured and the results were compared with the data obtained in control animals. The therapeutic dose caused only a nonsignificant increase of the content of microsomal proteins and the activities under study, while the tr eatment with the higher doses led to significant increases of the concentra tions of microsomal proteins and activities of 7-methoxyresorufin O-demethy lase and. 7-ethoxyresorufin O-deethylase. The results indicate the potentia l of ivermectin to induce the expression of cytochrome P4501A isoenzymes, w hich are known to be the biotransformation enzymes responsible for metaboli c activation of promutagenes.