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Effect of Ivermectin on Induction of Cytochromes P450 in Male Rats

L. Skálová, B. Szotáková, M. Machala, J. Neča, J. Lamka, L. Ducháček, and E. Kvasničková

Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, CZ-500 05 Hradec Králové

 

Abstract: Effects of the widely used antiparasitic drug ivermectin on cytochromes P450 were tested in adult male rats. Liver microsomes were prepared from animals after single or repeated treatments with various doses of ivermectin. The hepatic microsomal protein content and activities of cytochromes P450 towards alkoxyresorufins and testosterone as the specific substrate probes were 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 treatment with the higher doses led to significant increases of the concentrations of microsomal proteins and activities of 7-methoxyresorufin O-demethylase and. 7-ethoxyresorufin O-deethylase. The results indicate the potential of ivermectin to induce the expression of cytochrome P4501A isoenzymes, which are known to be the biotransformation enzymes responsible for metabolic activation of promutagenes.

Full paper in Portable Document Format: 544a249.pdf

 

Chemical Papers 54 (4) 249–253 (2000)

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