The effects of flubendazole and mebendazole on cytochromes P4501A in pheasant hepatocytes.
Many benzimidazoles are known inducers of cytochromes P4501A (CYP1A) in laboratory animals and cell lines. As flubendazole and mebendazole are benzimidazole anthelmintics often used in a pheasant, in the present study an effect of these drugs in primary cultures of pheasant (Phasianus colchicus) hepatocytes was investigated. After 48 h incubation of the hepatocytes with the benzimidazoles (0.2-5 microM), CYP1A activities -- ethoxyresorufin O-deethylation (EROD) and methoxyresorufin O-demethylation (MROD) activities were measured and the CYP1A protein levels were determined by Western blotting. None of the tested benzimidazoles influenced the CYP1A protein content. No pharmacologically significant enhancement of CYP1A after exposure of the hepatocytes to flubendazole and mebendazole was found. Inhibition of the EROD/MROD activities caused by both tested substances was observed only at the highest concentration (5 microM). From a point of view of CYP1A induction or inhibition, the treatment of pheasants by both anthelmintics tested seems to be safe. Our study demonstrates the inter-species differences in CYP1A inducibility and the importance of induction/inhibition studies on target animals.
Savlík
M
M
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. savlik@faf.cuni.cz
Polásková
P
P
Szotáková
B
B
Lamka
J
J
Skálová
L
L
D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D046094:Galliformes / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology*; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010088:Oxidoreductases / Q000187:drug effects
D000969:Antinematodal Agents; D008463:Mebendazole; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; C018945:flubendazole