Altered drug metabolism in parasitic diseases

While the immune system represents the main line of host defence against parasite infections, mixed function oxidase (MFO) systems (Box 1) offer the main line of defence against drugs and other biologically active substances. But, as this review shows, many parasites can exert a profound effect on the host MFO system by altering the microsomal drug-metabolizing enzymes and electron transport carriers such as cytochrome P-450. This can markedly affect the host's ability to metabolize biologically active compounds, often with adverse physiological, pharmacological and toxicological consequences. In mammals, drug metabolism occurs predominantly in the liver, and to a lesser extent in the spleen, lungs, kidneys, intestine and cerebral tissues. Thus those parasites that occupy sites in these tissues - such as amoebae, Fasciola, schistosomes and malaria - tend to be those with greatest effects on the host's ability to metabolize drugs. The effects can modify the host response to substances unrelated to the infection, and to drugs which may be administered under a chemotherapeutic regime.