Loss of substrate binding capacity of the hepatic microsomal cytochrome P-450 in Fasciola hepatica infected rats: toxicological implications

Experimental fascioliasis in the rat is responsible for a dramatic decrease in the drug-metabolizing ability of the hepatic monooxygenase system. The present investigation, through a spectroscopic study of hexobarbital interaction with microsomal cytochrome P-450 and in vitro and in vivo studies of hexobarbital metabolism in the rat, demonstrates that this decrease is due to an alteration in the structure of the hemoprotein (loss of substrate binding capacity of cytochrome P-450 followed by denaturation). These results might be responsible for a decreased safety margins for those flukicidal agents that are detoxified by the monooxygenase pathway, and might explain the accumulation problems frequently associated with chemotherapy of Fasciola hepatica.