Nematocidal activity of nitazoxanide in laboratory models.
The nematocidal activity of a broad-spectrum antiparasitic agent, nitazoxanide [( N-(5-nitrothiazol-2-gammal)salicylamide; NTZ], was evaluated in both in vitro and in vivo models using Caenorhabditis elegans, Heligmosomoides polygyrus and Trichinella spiralis. In vitro, NTZ (100 muM) exhibited a low activity against C. elegans and had no effect on embryonation and hatching of H. polygyrus eggs. At concentrations of 100 and 50 muM, the inhibition of excretion/secretion of acetylcholinesterase and acid phosphatase of adult H. polygyrus by NTZ was variable. The in vitro effects of mebendazole (5 muM), albendazole (1 muM) and levamisole (10 muM) were superior to those of NTZ. In mice, NTZ at 1 g/kg proved to be inactive against preadults of T. spiralis whereas mebendazole at 10 mg/kg reduced the worm burden by up to 83%. NTZ at 1 g/kg per day for 3 consecutive days showed a low activity against adults of H. polygyrus (21% reduction). Levamisole, at a single dose of 10 mg/kg, reduced the worm burden by up to 89.9%. The results of this study suggest that NTZ would not have met criteria of a candidate compound.
Department of Parasitology, Faculty of Pharmacy, Complutense University, 28040, Madrid, Spain.
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Fonseca-Salamanca
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MM
Martínez-Grueiro
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AR
Martínez-Fernández
D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001681:Biological Assay; D017173:Caenorhabditis elegans / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006369:Heligmosomatoidea / Q000187:drug effects; D051379:Mice; D009348:Nematoda / Q000187:drug effects; D009574:Nitro Compounds; D010273:Parasitic Diseases, Animal / Q000188:drug therapy*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D017160:Trichinella spiralis / Q000187:drug effects; D014235:Trichinellosis / Q000188:drug therapy*
D000969:Antinematodal Agents; D000977:Antiparasitic Agents; D009574:Nitro Compounds; D013844:Thiazoles; C041747:nitazoxanide