Schistosoma mansoni: biochemical characteristics of the antischistosomal effects of Ro 15-5458.
We evaluated a variety of biochemical parameters in Schistosoma mansoni isolated from mice up to 4 days after dosing with 15 mg/kg Ro 15-5458. While no drug effect could be demonstrated in the utilization of media glucose, glycogen content, gut pigment, or ATP levels of the parasites, a significant reduction (P less than or equal to 0.05) in parasite weight and protein content was observed. Possible drug actions that may contribute to the loss in parasite protein and perhaps ultimately result in parasite death have been investigated. We noted significant reduction in the incorporation of leucine and thymidine into acid-insoluble fractions of the parasites. The reduction in the incorporation of leucine into parasite proteins was nonspecific and preceded the effect of the drug on the uptake of the amino acid. Parasite and host liver RNA isolated after dosing were translated in vitro in a rabbit reticulocyte system. Drug-treated parasite mRNA, but not that of the host, was less effective than control mRNA in directing the incorporation of [35S]methionine. We propose a hypothesis that attributes the loss in protein content to a defect in the biosynthesis of parasite proteins as a result of a drug-induced reduction in the quantity of mRNA in the parasites This effect of Ro 15-5458 on the parasite may provide the basis for its schistosomicidal action.
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Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Bennett
J L
JL
D000166:Acridines / Q000494:pharmacology* / Q000627:therapeutic use; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050260:Carbohydrate Metabolism; D006224:Cricetinae; D003470:Culture Media; D005260:Female; D015801:Helminth Proteins / Q000096:biosynthesis; D007773:Lactates / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D010860:Pigments, Biological / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D012555:Schistosomiasis mansoni / Q000188:drug therapy*; D012556:Schistosomicides / Q000494:pharmacology* / Q000627:therapeutic use
D000166:Acridines; D003470:Culture Media; D015801:Helminth Proteins; D007773:Lactates; D010860:Pigments, Biological; D012333:RNA, Messenger; D012556:Schistosomicides; D000255:Adenosine Triphosphate; C062730:Ro 15-5458