Evaluation of the mode of action of albendazole against Giardia duodenalis
Oxberry, M., Reynoldson, J. and Thompson, R.C.A. (1997) Evaluation of the mode of action of albendazole against Giardia duodenalis. In: 46th annual meeting of the American Society of Tropical Medicine and Hygiene, 7 - 11 December, Lake Buena Vista, Florida.
Giardia duodenalis, a protozoan parasite, is the most common intestinal parasite of humans in the world today. The disease is of particular importance amongst children in developing countries in whom recurrent infection can lead to malabsonption and failure to thrive. Treatment with the currently used antigiardial agents is not completely satisfactory as side effects are fairly common and the parasite is not always eliminated from the host. Therefore the discovery that albendazole, a member of the benzimidazole group of anthelmintics, was effective against C. duodenalis was a significant finding as these drugs are very safe and are also effective against several other intestinal parasites of humans. It is believed that the benzimidazoles exert their effect in helminth parasites by binding to tubulin and disrupting its polymerisation into microtubules. This study was conducted in order to determine the mode of action of albendazole against G. duodenalis. Techniques used included drug binding and displacement studies involving C. duodenalis proteins. It was found that tritiated albendazole bound most strongly to the tubulin protein of C. duodenalis (confirmed using an anti-tubulin antibody) and binding was most concentrated amongst the smaller microtubule fragments. Binding of tritiated albendazole could be displaced from tubulin using unlabelled albendazole and other benzimidazoles. The order of displacement by the various compounds corresponded to the order of potency of the drugs against the parasite. The results of this study suggest that the benzimidazoles bind to and disrupt C. duodenalis tubulin but further work is required to determine whether this is the primary mode of action of this drug.
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