Incidence of experimental fascioliasis on the activity of drug-metabolizing enzymes in lamb liver.
The purpose of this investigation was to determine the effects of a subclinical fascioliasis at various stages of its development (by week--4, 8, 12, and 16 weeks after the infestation by an oral administration of 150 metacercariae of Fasciola hepatica) on the activity of some hepatic drug-metabolizing systems in lamb. The parasitic pathology was ascertained at autopsy and by clinical observation of animals. Hepatic microsomal cytochrome P-450 content was significantly decreased (by 9-22%) in all infected groups of animals. In early stages of the parasitic disease, decreases in cytochrome b5 content (10-18%) and ethoxycoumarin O-deethylase (25%) were observed, whereas aminopyrine N-demethylase, benzphetamine N-demethylase, and aniline hydroxylase were significantly lowered by 8 to 16 weeks postinfection. Among investigated transferases, glutathione transferase was only decreased (28%) in animals killed 16 weeks after the infestation; in these animals a significant increase in microsomal gamma-glutamyltransferase was observed, probably related to the elevated plasma activity of this enzyme. By 8 weeks postinfection, a simultaneous increase in cytosolic calcium (38%) and decrease in cytosolic glutathione (22%) would correspond to an oxidative cell injury occurring in the course of fascioliasis. The consequences of the fascioliasis-induced decreases in liver-oxidative and conjugative liver drug metabolism are discussed.
Galtier
P
P
Larrieu
G
G
Tufenkji
A E
AE
Franc
M
M
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005211:Fascioliasis / Q000201:enzymology*; D005969:Glutamate Dehydrogenase / Q000032:analysis; D007064:L-Iditol 2-Dehydrogenase / Q000032:analysis; D008099:Liver / Q000201:enzymology*; D008297:Male; D010105:Oxygenases / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012756:Sheep; D005723:gamma-Glutamyltransferase / Q000032:analysis
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D007064:L-Iditol 2-Dehydrogenase; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D005969:Glutamate Dehydrogenase; D005723:gamma-Glutamyltransferase