Fenbendazole for Humans and Pheasants

Fenbendazole is an anthelmintic used in human medicine to treat parasitic worm infections. It also has anticancer properties. It is a potent microtubule destabilizing agent that has been shown to have multiple mechanisms of action in cancer cells and promotes cell death through modulation of several cellular pathways. FDA has not approved fenbendazole-medicated feed for pheasants, but it is commonly administered in an extra-label manner to control nematode parasitism in these birds. Since fenbendazole has a low oral bioavailability, high levels of drug residues are anticipated in slaughtered pheasants. Estimating the risk of consuming pheasant meat contaminated with fenbendazole residues is important for determining safe tolerance and maximum residue limits (MRLs) for the compound in food products. Deterministic and stochastic approaches that consider diverse adverse outcomes including repeat-dose toxicity, reproductive toxicity, and carcinogenicity have been utilized for this purpose.

Using an A549 human lung carcinoma cell line, we investigated whether fenbendazole (FZ) could disrupt the mitotic checkpoint by inhibiting tubulin polymerization in vitro. The results indicated that FZ treatment caused a significant increase in cyclin B1 protein level and an arrest of the cell cycle at the G2/M transition. This effect is attributable to the inhibition of cyclin-dependent kinase 1 (CDK1) activity by FZ and is likely a mechanism for the anticancer activity of this compound.

We next determined whether fenbendazole could synergistically enhance the antineoplastic effects of taxanes. In a dose-response study, the growth curves of EMT6 tumors were evaluated after irradiation with 10 Gy in the presence of different combinations of three daily injections of either fenbendazole alone or fenbendazole plus paclitaxel. Survival data showed that the combination of these drugs produced additive cytotoxicities, consistent with their mechanisms of action.fenbendazole for humans

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