Hymenolepis diminuta: effects of amoscanate on energy metabolism and ultrastructure.
Amoscanate possesses chemotherapeutic activity against schistosomes, and in higher doses against many other helminths including filariids and Hymenolepis diminuta. The primary mode of action of this compound is unknown. Effects of the drug on the carbohydrate metabolism as well as on the tegumental and nephridial epithelia of H. diminuta were examined. At various time intervals after administration of the drug to rats infected with H. diminuta, the parasites were recovered and incubated in glucose-salts medium for 90 min. Chemotherapy resulted in decreases in succinate, lactate, and acetate recoveries, while ATP levels dropped. In addition, glycogen levels were depressed in drug-treated worms which were homogenized immediately upon isolation. Glycogen synthase I activity was inhibited 16-61% in cestodes obtained from Amoscanate-treated animals and homogenized immediately, but returned to normal levels after incubation for 90 min in glucose-salts medium prior to homogenization and assay. Phosphorylase a activity was found to be 25-30% higher in preparations of worms from drug-treated rats, which correlates with the rapid depletion of glycogen in parasites exposed to the drug. However, in contrast with glycogen synthase activity, the elevation of phosphorylase a activity in H. diminuta exposed to the drug was not readily reversible. Attempts to demonstrate activity of the drug in vitro by incubating intact cestodes directly with Amoscanate were unsuccessful. Thin sections of parasites obtained from Amoscanate-treated rats and examined by transmission electron microscopy revealed surface alterations of the tegument and nephridial canals. Alterations included bleb formation and erosion of microtriches from the tegument, as well as disappearance of microvilli from nephridial canals. However, these effects became manifest only after 4 or more hr exposure of the rat to the drug. Biochemical effects, on the other hand, were significant after 3 hr exposure.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006925:Hymenolepiasis / Q000469:parasitology; D006926:Hymenolepis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017879:Isothiocyanates; D008297:Male; D008854:Microscopy, Electron; D008871:Microvilli / Q000648:ultrastructure; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D013861:Thiocyanates / Q000494:pharmacology*
D000814:Aniline Compounds; D000871:Anthelmintics; D017879:Isothiocyanates; D013861:Thiocyanates; D000255:Adenosine Triphosphate; D006003:Glycogen; D004159:Diphenylamine; D006005:Phosphorylases; D006006:Glycogen Synthase; D005947:Glucose; C012391:amoscanate