Changes in Hepatic Phase-I and -II Drug-metabolizing Enzymes and Antioxidant Capacity in Egyptian Ovine Fascioliasis Treated with Triclabendazole

Sheep experimentally infected with the Egyptian strain of Fasciola were used to study the influence of infection on the activities of some drug-metabolizing enzymes and antioxidant capacity in the liver. Twentytwo sheep were randomly divided into a group of 12 animals (all subsequently infected with 150 metacercariae of Fasciola) and a group of ten (left uninfected, as normal controls). Three months post-infection, seven of the infected sheep were treated with triclabendazole (TCBZ) as a single oral dose of 10 mg/kg b.wt. and the other five were left untreated. The uninfected sheep were, similarly, treated with TCBZ (n=5) or left untreated (n=5). Four weeks after the end of treatment, the animals were ethically slaughtered. Significant decreases (40-53%) were observed in the hepatic microsomal contents of cytochrome P450 (CYP450; P < 0.001), cytochrome b5 (Cyt b5; P < 0.001) and aminopyrine N-demethylase, aniline 4-hydroxylase (P < 0.01) and glutathione S-transferase (GST; P < 0.05) activities when compared with the uninfected untreated sheep. Moreover, reduced glutathione (GSH) content; glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly lowered by 33.25%, 40% and 53.35% respectively. Meanwhile, glutathione reductase (GR) activity and malonaldehyde (MDA) level were significantly elevated by 66.92% (P < 0.05) and 65.79% (P < 0.001) respectively. Treatment with TCBZ restored all previously measured parameters to their normal levels. In conclusion, Egyptian fascioliasis impaired oxidative, conjugative drug metabolism and induced oxidative stress. This study also confirms that TCBZ is the ideal fasciocidal drug for recovery of all the disease-related pathogenic factors.