Effect of oltipraz on the susceptibility of adult Schistosoma mansoni to killing by mouse peritoneal exudate cells.
Incubation of the adult Schistosoma mansoni with the anti-schistosomal compound oltipraz (OPZ) (40 nM) resulted in a significant decrease in schistosome-reduced glutathione (GSH), a thiol compound which may have a role in protection against oxidant-mediated damage. A significant proportion (20-47%) of worms treated with OPZ became susceptible to in vitro killing by zymosan-stimulated peritoneal exudate cells from mice infected with S. mansoni or inoculated with Bacillus Calmette Guérin (BCG). Killing of the worms was partially inhibited by the addition to the assay system of exogenous glutathione peroxidase with GSH but not by superoxide dismutase. These results suggested that killing of parasites exposed to the drug was partly mediated by cell-generated hydrogen peroxide. They indicate also that depletion of schistosome GSH levels could render the parasites susceptible to killing by oxidative mechanisms, and suggest that there is potential in exploiting schistosome oxidant defense systems and reactive oxygen byproducts in the treatment of schistosomiasis. Inhibition of schistosome oxidant defense systems with drugs may render the parasites susceptible to killing by reactive oxygen byproducts of effector cells.
Mkoji
G M
GM
Institute of Parasitology of McGill University, Macdonald College, Ste-Anne de Bellevue, QC, Canada.
Smith
J M
JM
Prichard
R K
RK
D000818:Animals; D005978:Glutathione / Q000032:analysis; D007111:Immunity, Cellular / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010529:Peritoneal Cavity / Q000166:cytology; D010586:Phagocytes / Q000276:immunology*; D011719:Pyrazines / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000032:analysis / Q000187:drug effects* / Q000276:immunology; D012556:Schistosomicides / Q000494:pharmacology*; D013871:Thiones; D013876:Thiophenes
D011719:Pyrazines; D012556:Schistosomicides; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; D005978:Glutathione