Fenben lab fenbendazole is a benzimidazole, with activity against numerous nematodes, cestodes and trematodes. Efficacy of fenbendazole has been demonstrated for nematodes such as Aelurostrongylus abstrusus, Ancylostoma tubaeforme, Baylisascaris procyonis, Crenosoma vulpis and Eucoleus stenocephala; cestodes including Taenia solium, Heterobilharzia americana and Strongyloides stercoraria; and trematodes including Heterobilharzia parva, Neoparagonimus malaris and Paragonimus kellicotti.
The mode of action of fenbendazole is to block synthesis of cell-dimerizing proteins in the parasites by binding to b-tubulins. This inactivation of the synthesis and assembly of microtubules halts normal cell functions, including protein synthesis, causing rapid death. The drug is also believed to interfere with glucose metabolism, preventing the growth of tumor cells by inhibiting the formation of ATP and preventing proliferation of neoplastic cells through inhibition of mitosis.
Although fenbendazole is relatively safe in livestock and other mammalian species, long-term exposure of humans to the drug can result in a variety of side effects, ranging from psychiatric disturbances to liver disease. These side effects may be due to interactions with other medications, or may be due to toxicity of the drug itself, especially at high doses. The risk of toxicity is reduced by administration of the drug in conjunction with other medications (e.g., antipsychotics) or by limiting the duration of treatment to a minimum of 6 months.
Infection with Aspiculuris tetraptera pinworms remains problematic for many animal facilities, despite effective treatment regimens that include fenbendazole-medicated diets and the use of PCR testing to confirm positive diagnoses. Pinworm infestations are a serious problem in research rodent colonies and may be difficult to eradicate completely, due to nonvigorous decontamination procedures, animal movement within facilities by investigators, and shared cages.
A well-established murine lymphoma xenograft model typically results in 80% to 100% successful tumor growth within 21 d, and can be used to examine the role of mitochondrial genes in tumorigenesis. In a study at our institution, fenbendazole-medicated feeding prevented tumor growth in mice implanted with human lymphoma xenografts. In addition, when a combination of vitamin antioxidants and fenbendazole was used in the diet, synergistic antitumor activity was observed. The exact mechanism for this interaction is unknown, but the researchers speculate that the vitamin antioxidants enhance fenbendazole’s effect by interfering with mechanisms that play a role in tumorigenesis. Although these findings were unexpected, they suggest that the veterinary community should be aware of possible unforeseen effects of fenbendazole-medicated rodent diets to better advise colleagues. A comprehensive catalog of fenbendazole’s unintended effects is unlikely to be fully developed, and new ones will likely be identified as the use of this drug continues to increase. The research veterinary community must be prepared to identify these unforeseen effects so that they can be communicated effectively to other scientists and avoided when possible. The use of fenbendazole-medicated feed in research rodents should be restricted to the extent possible, given the potential for confounding results. fenben lab fenbendazol