title: Nematocidal activities of thiabendazole and ivermectin against the larvae of Strongyloides ratti and S. venezuelensis.
abstract: With the aim of developing therapeutic agents for strongyloidosis, the disease caused by infection with Strongyloides stercoralis, we established a novel assay technique using S. ratti and S. venezuelensis as models for S. stercoralis. The newly developed assay technique was found to more accurately represent treatment-induced larval paralysis than existing assays. Our method uses paper disks impregnated with the test solution, which even allows materials that are sparingly soluble in water to be tested. An inverted microscope was used to observe the larval states, and these states were recorded using a digital camera. We observed the activities of ivermectin and thiabendazole against larvae and calculated larval motility and velocity. These two factors were then combined to determine the overall viability of larvae at selected concentrations. The activities of the anthelmintics were compared by calculating the concentrations at which 50% viability was demonstrated, or in other words, the concentration at which paralysis was caused in 50% of the individuals (50% paralysis concentration; PC(50)). Evaluations after 24h of exposure yielded the following reproducible PC(50) values for ivermectin and thiabendazole, respectively: S. ratti, 2.4 and 140 microM; and S. venezuelensis, 2.3 and 190 microM. After treatment with ivermectin, there was a tendency for larval motility to be greater than that of the controls at low concentrations, a result that might be associated with its mechanism of action.
authors.affiliation: Department of Pharmacognosy, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 2748510, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Satou
authors.forename: M
authors.initials: M
authors.lastname: Koga
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: I
authors.initials: I
authors.lastname: Tada
authors.forename: T
authors.initials: T
authors.lastname: Nikaido
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005243:Feces / Q000469:parasitology; D007559:Ivermectin / Q000494:pharmacology* / Q000627:therapeutic use; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D007928:Lethal Dose 50; D051381:Rats; D017206:Strongylida Infections / Q000188:drug therapy*; D013321:Strongyloides / Q000187:drug effects* / Q000254:growth & development; D017170:Strongyloides ratti / Q000187:drug effects / Q000254:growth & development; D013827:Thiabendazole / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000969:Antinematodal Agents; D007559:Ivermectin; D013827:Thiabendazole