Effects of benzimidazole anthelmintics as microtubule-active drugs on the synthesis and transport of surface glycoconjugates in Hymenolepis microstoma, Echinostoma caproni, and Schistosoma mansoni.
Hymenolepis microstoma (Cestoda), Echinostoma caproni, and Schistosoma mansoni (Digenea) were exposed to benzimidazoles to determine the influence of the drugs on the secretion of glycoconjugates that protect the worms' surface. Worms were obtained from mice treated with mebendazole or albendazole, and the glycoconjugates were localized in the parasite tissues by cytochemistry using lectin-gold conjugates. Events leading to the death of H. microstoma and E. caproni extended over a medication period for at least 2-3 days, and the following interrelated phases were discernible. Upon depolymerization of the microtubules the tegumentary cytons continued to synthesize glycoconjugates for up to about 24 h. Vesicles containing the glycans accumulated in the cytons, but their microtubule-based transport to the distal tegument was inhibited. At about 1 day the Golgi complex became fragmented and the production of glycans sharply declined. As a consequence of this and an ongoing turnover of the surface coat the contents of glycoconjugates in the distal tegument decreased. Similar effects were produced by vinblastine and colchicine in vitro. In contrast, benzimidazole treatment of S. mansoni, which is reportedly inefficacious, did not alter the replenishment of the surface glycoconjugates. Diminution of the coating with glycoconjugates of the surface of drug-sensitive species constitutes a secondary effect of benzimidazoles that might, synergistically with immune mechanisms of the host, enhance the expulsion of the worms.
Schmidt
J
J
Institut für Spezielle Zoologie, Ruhr-Universität, Bochum, Germany.
D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004449:Echinostoma / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006001:Glycoconjugates / Q000096:biosynthesis / Q000378:metabolism*; D006651:Histocytochemistry; D006926:Hymenolepis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008463:Mebendazole / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016610:Tissue Embedding; D016707:Tissue Fixation
D000871:Anthelmintics; D001562:Benzimidazoles; D006001:Glycoconjugates; D008463:Mebendazole; D015766:Albendazole