Spectrum Chemical manufactures and distributes fine chemicals with quality you can trust including fenben lab fenbendazol Also known as methyl 5-(phenylthio)-2-benzimidazolecarbamate.
Textbook depictions of cells show various organelles floating in amorphous bags of liquid, but in truth, these organisms establish shape and structure through the protein scaffolding known as microtubules.
Toxicity
Fenbendazole is an anthelmintic drug used to treat parasites including pinworms, giardia, roundworms, hookworms and Taenia solium (pulmonary paragonimiasis). It exerts its antiparasitic action by binding to tubulin and inhibiting its polymerization. Tubulin is an essential component of microtubules, which form part of the cytoskeleton. Inhibition of microtubules causes cell death by a number of mechanisms. It is often used in combination with cytotoxic anticancer agents.
In vitro and in vivo studies have shown that fenbendazole exacerbates the hepatotoxicity of acetaminophen in vultures of the species G. coprotheres. This is most likely due to a reduction in the levels of hepatic GSH, which is required for the detoxification of NAPQI. GSH levels decrease rapidly after acetaminophen administration and remain suppressed in mice fed a fenbendazole-containing diet (Fig. 1).
This study indicates that fenbendazole reduces hepatic GSH levels, which could lead to an increased exposure of the liver to xenobiotics such as acetaminophen. Therefore, caution should be taken when combining this drug with drugs that require the oxidation of glutathione such as some of the vinca alkaloids. Additionally, the presence of hepatic CYP enzymes should be considered in the design of therapeutic strategies using this drug. It is also important to determine whether hepatic GSH is affected by fenbendazole in other avian species. Similar effects have been reported for diclofenac in White-backed Vultures (G. rauginensis) and Lappet-faced Vultures (Torgos tracheliotus) and the need to assess whether these species are susceptible to fenbendazole toxicity should be further explored.
Side Effects
Fenbendazole is an effective anti-worm drug. It is a commonly used cattle dewormer, and it also has anti-cancer and anti-viral properties. It has been shown to inhibit the growth of certain cancer cells and can prevent the recurrence of certain types of leukemias. It also has anti-inflammatory effects and can suppress inflammatory mediators in the blood.
Several studies have demonstrated the ability of fenbendazole to reduce tumor growth and suppress the formation of new cells in vivo (animal) models. In one study, 1 mg/mouse of fenbendazole was administered every other day for 12 days to athymic nu/nu mice with human nonsmall cell lung carcinoma (A549) cells, and a significant reduction in tumor volume was observed.
Cell viability was assessed by counting colonies formed from monolayer cultures that had been treated for 2 or 24 h with varying doses of fenbendazole. Survivals were normalized to yield-corrected numbers of cells in the cultures at the end of treatment, and plotted on a dose-response curve with docetaxel as a control. Additive toxicities were observed when the survival data were plotted on a docetaxel concentration-response curve, and the results were confirmed by isobologram analyses (Figure 1).
In another animal model, an unreported number of BALB/c mice received either fenbendazole or vehicle from birth until weaning. Treatment resulted in a significantly greater decrease in tumor size and weight, as well as a reduction in hepatic and intestinal metaplasia. Furthermore, in a mouse model of allergic airway disease induced by ovalbumin exposure, fenbendazole treatment reduced the percentage composition of leukocytes and goblet cells in lung sections, and reduced the levels of eosinophils in bronchoalveolar lavage fluid.
Dosage
Fenbendazole (brand name Vermox) is a broad-spectrum benzimidazole anthelmintic that is used to treat gastrointestinal parasites such as giardia, roundworms, hookworms, whipworms and the tapeworm genus Taenia. It also has been used off-label to treat trematodes associated with gastrointestinal disease such as Heterobilharzia americana and Platynosomum fastosum.
Febendazole has no known effects on other normal cells and does not disrupt the organic function of host cells. It acts as an anthelmintic by binding to b-tubulin, which is part of the microtubules of the cell. Microtubules are the structure and support for a variety of other structures including chromosomes, spindles, microvilli, and microtubule-associated proteins. It is believed that fenbendazole prevents the formation of these structures by inhibiting the polymerization of tubulin.
The drug is poorly absorbed when administered orally and reaches a maximum concentration in blood within 48 hours. It is converted to its active sulfoxide and sulfone metabolites in the liver, which are excreted in the urine and feces.
In animal studies, fenbendazole has been shown to have antitumor activity. It has been reported to be cytotoxic to cancer cells and may enhance the antineoplastic effect of radiation and nitroheterocyclic chemotherapeutic drugs. However, these reports haven’t been backed by scientific evidence from randomized controlled trials. The anecdotal account of Joe Tippens, a lung cancer patient, suggests that fenbendazole has potential as a tumor-treating agent in humans.
Interactions
The benzimidazole class of drugs, including fenbendazole, has been shown to interact with other products. These products include folic acid and iron supplements. In one study, fenbendazole reduced the effectiveness of these products. The interaction was due to the drug binding to b-tubulin, which inhibits microtubule assembly and disrupts cell cycle progression. The drug also reduces the concentration of a protein called cyclin B1, which is involved in cell cycle regulation.
The anticryptococcal activity of fenbendazole is mediated by inhibition of the growth of microtubules and the disruption of cellular processes that are important in capsule formation. It has been shown that fenbendazole has profound effects on capsule density and dimensions, as well as intracellular proliferation rates and events required for phagocytic escape by macrophages. This activity is similar to that of the standard antifungal agent amphotericin B. Fenbendazole is not toxic to mammalian cells.
Although there is evidence that fenbendazole has anticancer effects in cancer cell cultures and animals, it is not known whether these results can be extended to human cancer patients. This is important because fenbendazole may interfere with conventional chemotherapy, which is the main treatment for cancer in humans. Tippens’ anecdotal experience is intriguing, but it’s not clear how much fenbendazole contributed to his remission. To determine whether fenbendazole has anticancer activity in humans, large randomized controlled trials would need to be performed.