Mouflon (Ovis musimon) dicrocoeliosis: effects of parasitosis on the activities of biotransformation enzymes and albendazole metabolism in liver.
Parasitic infections can modify the host's ability to metabolize drugs and other xenobiotics by altering the biotransformation enzymes; these changes may have various pharmacological, toxicological or physiological consequences. In our study, several activities of liver biotransformation enzymes and in vitro metabolism of albendazole (ABZ) were tested and compared in non-infected mouflons (Ovis musimon) and in mouflons infected by lancet fluke (Dicrocoelium dendriticum). Subcellular fractions of liver homogenates were isolated from 5+5 mouflon rams (1-year-old) parasitologically negative or naturally infected by fluke. From the eight enzyme activities that were assayed, only two activities significantly differ in the case of Dicrocoelium-infected versus non-infected animals. In infected mouflons, a significant increase (53%) of thiobenzamide-S-oxidase (TBSO) activity, corresponding mainly to the activity of flavine monooxygenase (FMO), and significant decrease (60%) of glutathione-S-transferase (GST) activity was observed. In addition, dicrocoeliosis caused the enhancement of ABZ hepatic biotransformation. The velocity of the formation of (+)-ABZ sulfoxide and ABZ sulfone was significantly increased. However, the shifts in ABZ biotransformation were very mild that undesirable alterations in ABZ pharmacokinetic are not expected. From this point of view, the use of ABZ in the therapy of mouflon dicrocoeliosis in young animals can be recommended. The treatment of the same mouflons by other drugs that are mainly conjugated with glutathione, seems to be more problematic; hence, all consequences of documented reduced GST activity should be accounted.
Skálová
L
L
Charles University in Prague, Faculty of Pharmacy, Heyrovského 1203, Hradec Králové, Czech Republic. lenka.skalova@faf.cuni.cz
Krízová
V
V
Cvilink
V
V
Szotáková
B
B
Storkánová
L
L
Velík
J
J
Lamka
J
J
D015766:Albendazole / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000493:pharmacokinetics*; D004011:Dicrocoeliasis / Q000378:metabolism / Q000662:veterinary*; D008099:Liver / Q000378:metabolism*; D015394:Molecular Structure; D012756:Sheep; D012757:Sheep Diseases / Q000378:metabolism*
D000871:Anthelmintics; D015766:Albendazole