Effect Of Fenbendazole Research Articles

Redox-mediated Anticancer Activity of Anti-parasitic Drug Fenbendazole in Triple-negative Breast Cancer Cells.

An increasing number of studies are reporting anticancer activity of widely used antiparasitic drugs and particularly benzimidazoles. Fenbendazole is considered safe and tolerable in most animal species at the effective doses as an anthelmintic. Little is known about the redox-modulating properties of fenbendazole and the molecular mechanisms of its antiproliferative effects. Our study aimed to investigate the possibility of selective redox-mediated treatment of triple-negative breast cancer cells by fenbendazole without affecting the viability and redox status of normal breast epithelial cells. The experiments were performed on three cell lines: normal breast epithelial cells (MCF-10A) and cancer breast epithelial cells (MCF7 - luminal adenocarcinoma, low metastatic; MDA-MB-231 - triple-negative adenocarcinoma, highly metastatic). Cells were treated with fenbendazole for 48-h and three parameters were analyzed using conventional assays: cell viability and proliferation, level of intracellular superoxide, and level of hydroperoxides. The data demonstrated that MDA-MB-231 cells were more vulnerable to fenbendazole-induced oxidative stress than MCF-7 cells. In normal breast epithelial cells MCF-10A, fenbendazole significantly suppressed oxidative stress compared to untreated controls. These data correlate with the effect of fenbendazole on cell viability and the IC50 values, which is indirect evidence of the potential targeting anticancer effect of the drug, especially in MDA-MB-231 cells. The difference in the levels of oxidative stress induced by fenbendazole in MDA-MB-231 and MCF-7 indicates that the two types of breast cancer respond to the drug through different redox-related mechanisms.

Environmentally-realistic concentrations of anthelmintic drugs affect survival and motility in the cosmopolitan earthworm Lumbricus terrestris (Linnaeus, 1758)

Anthelmintic drugs are used to control intestinal parasitic worms in animals worldwide. Although generally effective in managing animal health, such treatment can introduce anthelminthic compounds to the wider environment as active ingredients and metabolites are often excreted. This can have detrimental effects on non-target species, especially when drugs are used excessively. Here, we examine the effects that two environmentally-realistic concentrations of four anthelminthics have on the common earthworm Lumbricus terrestris (Linnaeus, 1758), a species with a cosmopolitan distribution and that is often vital in maintaining functional edaphic ecosystems. The drugs were ivermectin (0.502 and 2.511 mg kG−1 active ingredient), fenbendazole (0.309 and 1.547 mg kG−1), pyrantel (79.480 and 397.400 mg kG−1), and praziquantel (2.299 and 11.499 mg kG−1): these concentrations were typical of soils where pasture grazed by animals treated with anthelminthics. Both lethal effects (mortality) and sub-lethal effects (motility) were considered. Earthworms exposed to fenbendazole and praziquantel over a 12-week period experienced high mortality (55.0% and 32.5%, respectively). Mortality rates among earthworms exposed to pyrantel and ivermectin were much lower (2.5% and 7.5%, respectively). However, earthworms exposed to pyrantel and ivermectin suffered decreased motility (time to burrow into substrate when exposed to heat and light) relative to a control group. Burrowing times were up to 40% longer for pyrantyl-exposed earthworms and 28% longer for ivermectin-exposed earthworms. For both drugs, the magnitude of the effect increased as concentration increased; all differences were statistically significant. There was little effect of fenbendazole and praziquantel on motility. Based on this study, which is seemingly the first to examine effects of ivermectin/fenbendazole on earthworm motility and the first to consider any effects of praziquantel/pyrantel, we conclude that environmentally-realistic concentrations of all four anthelmintics have sub-lethal (pyrantel and ivermectin) or lethal (fenbendazole and praziquantel) effects on a vital keystone species. Methods to reduce carry-over effects in ecologically-important, non-target, organisms should be urgently sought and care should be taken not to use anthelminthics routinely without first testing helminth burden to determine whether there is clinical need.

Metabolism of the anthelmintic drug fenbendazole in Arabidopsis thaliana and its effect on transcriptome and proteome

Fenbendazole, a broad spectrum anthelmintic used especially in veterinary medicine, may impact non-target organisms in the environment. Nevertheless, information about the effects of fenbendazole in plants is limited. We investigated the biotransformation of fenbendazole and the effect of fenbendazole and its metabolites on gene expression in the model plant Arabidopsis thaliana. High-sensitive UHPLC coupled with tandem mass spectrometry, RNA-microarray analysis together with qPCR verification and nanoLC-MS proteome analysis were used in this study. Twelve fenbendazole metabolites were identified in the roots and leaves of A. thaliana plants. Hydroxylation, S-oxidation and glycosylation represent the main fenbendazole biotransformation pathways. Exposure of A. thaliana plants to 5 μM fenbendazole for 24 and 72 h significantly affected gene and protein expression. The changes in transcriptome were more pronounced in the leaves than in roots, protein expression was more greatly affected in the roots at a shorter period of exposure (24 h) and in leaf rosettes over a longer period (72 h). Up-regulated (>2-fold change, p < 0.1) proteins are involved in various biological processes (electron transport, energy generating pathways, signal transduction, transport), and in response to stresses (e.g. catalase, superoxide dismutase, cytochromes P450, UDP-glycosyltransferases). Some of the proteins which were up-regulated after fenbendazole-exposure probably participate in fenbendazole biotransformation (e.g. cytochromes P450, UDP-glucosyltransferases). Finally, fenbendazole in plants significantly affects many physiological and metabolic processes and thus the contamination of ecosystems by manure containing this anthelmintic should be restricted.

Effect of fenbendazole in water on pigs infected with Ascaris suum in finishing pigs under field conditions

The husbandry of pigs for meat production is a constantly developing industry. Most studies on the effects of Ascaris suum infection in pigs and its prevention with anthelmintics are over a decade old. We examined the effect of 2.5mg fenbendazole per kg bodyweight administered in drinking water for two consecutive days on A. suum infection 1 and 6 weeks after pigs arrived to fattening units. We hypothesised that the treatment would reduce the presence of A. suum-infections, improve the average daily weight gain of pigs, reduce the percentage of liver rejections in pens by 50% and increase the lean meat percentage at slaughter by 1%.The study included a placebo group (427 pigs) and a treatment group (420 pigs) spanning four different farms previously reporting ≥15% liver rejection. The treatment was given for 2 consecutive days 1 and 6 weeks after the pigs arrived to the fattening unit. Faecal samples were collected during weeks 1, 6 and 12 from all pigs and examined for A. suum eggs. Blood was collected during weeks 1 and 12 from a subgroup of the pigs and examined for anti-A. suum antibodies and clinical blood parameters. Data on liver rejection and lean meat percentage were collected post-mortem.The proportion of Ascaris seropositive pigs changed from 8.6% to 22.2% and 20.3% to 16.3% in the placebo and treatment group respectively. Fenbendazole reduced the presence of A. suum eggs in faeces the percentage of liver rejections by 69.8%. The treatment did not affect daily weight gain or lean meat percentage. Pigs with A. suum eggs in faeces at week 6 had a lower average daily weight gain of 61.8g/day compared with pigs without parasite eggs.Fenbendazole treatment may be a useful option for farms struggling with persistent A. suum problems and demonstrate a beneficial effect on the weight gain of the animals shedding eggs in faeces and result in fewer condemned livers at slaughter.

Methyl N-(6-Phenylsulfanyl-1h-Benzimidazol-2-Yl) Carbamate: A Non-Toxic Substitute of Colchicine for Quality Metaphase Chromosome Preparation from Normal and Tumor Cells for Cytogenetic Analysis

Background: Methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate [Fenbendazole, FZ] is an anthelmintic drug which acts by selectively binding to β tubulin of nematodes, inhibiting the tubulin polymerization and blocking microtubule dependent glucose uptake. The anti-proliferative effect of Fenbendazole is partly due to its ability to affect microtubule dynamics and arrest cells at a pro-metaphase state with an intact mitotic spindle. Findings: Here, we show that Fenbendazole - a benzimidazole anthelmintic drug, can be used as an alternative to colchicine for making high quality chromosome preparations for karyotyping and further cytogenetic analysis. This drug could efficiently block the proliferation of human tumor cell lines as well as peripheral blood lymphocytes in culture by arresting them at G2M phase. FZ treatment at 1uM concentration for 3 h resulted in high mitotic indices resulting in a number of well spread metaphasic plates in suspension as well as adherent cultures. The morphology of metaphase chromosomes obtained from FZ treated samples was at par with those prepared from colchicine. Conclusion: Altogether, our results show FZ as an extremely efficient, relatively non-toxic and inexpensive G2/M blocker which may be utilized as a suitable alternative of colchicine for routine cytogenetic analysis.

Effect of fenbendazole on shedding and embryonation of Ascaris suum eggs from naturally infected sows

Objectives: To determine reduction of Ascaris suum egg shedding and ovicidal effects in naturally infected commercial female breeding swine treated with fenbendazole. Materials and methods: Five shedding and three embryonation experiments across three commercial sow farms were conducted. Ascaris suum-infected sows were allocated to four treatments: untreated controls; 545.5 mg fenbendazole, 1 day (Treatment 1); 545.5 mg fenbendazole, 3 consecutive days (1636.5 mg total) (Treatment 2); and 1636.5 mg fenbendazole, 1 day (Treatment 3). Fecal samples were collected and evaluated by a standard flotation method (shedding study) or eggs were isolated and incubated (embryonation study) to determine embryonation rates. Groups were compared for time-to-negative (Kaplan-Meier survival analysis); percent negative (chi-square analysis); environmental burden (analysis of variance); and embryonation rates (analysis of variance). Results: Time-to-negative ranges were 9.3-13.1, 8.9-13.1, and 9.8 days post treatment (DPT) for treatments 1, 2, and 3, respectively; control ranges were 13.4-28.2 DPT. Treatment sows were 90%-100% negative, compared to 0.0%-28.6% of controls. Environmental burden ranges were 7.0%-60.9%, 13.9%-60.8%, and 29.3% (treatments 1, 2, and 3, respectively) and 60.4%-219.0% for controls. All treatment values differed from controls (P &lt; .05), but not from each other. Embryonation rates were lower for treatments than controls at 6 and 8 DPT (P &lt; .001). Implications: Fenbendazole at various dosages is effective against A suum infections in sows. Treatment should begin 14 days prior to movement into clean farrowing facilities. Under the conditions of this study, fenbendazole demonstrates ovicidal activity against A suum at 4-8 DPT.

Effect of fenbendazole on growth promotion in Mecheri lambs

Aim: The objective of the study was to find out the effect of fenbendazole on the growth promotion in stunted mecheri lambs. Materials and methods: The study was conducted with three groups of ten mecheri lambs each. Group I served as untreated control and group II and III were treated with fenbendazole @ 5 mg/kg body weight and 7.5 mg/kg body weight, respectively. All the lambs were subjected to haemato-biochemical observations, body weight recording and collection of faeces for egg counting before and after the treatment. Results: Fenbendazole in both the doses had beneficial effect on haemato-biochemical observations like haemoglobin, total erythrocyte count, total protein, albumin, aspartate aminotransferase and alanine aminotransferase besides showing efficacy as an anthelmintic. The drug also increased body weight gain significantly at higher dose as compared to untreated control. Conclusion: The results support that fenbendazole has the potential for modulating growth of stunted mecheri lambs.

Preliminary studies on the effect of fenbendazole and oxfendazole on Taenia saginata cysticerci in calves.

Summary Oxfendazole given orally to calves in doses of 50 mg./kg. or 100 mg./kg. body weight and fenbendazole at 100 mg./kg. or 4 × 50 mg./kg. had no lethal effect on 10-week-old cysticerci of Taenia saginata. Zusammenfassung Orientierende Untersuchungen uber die Wirkung von Fenbendazol und Oxfendazol auf Cysticercus bovis beim Kalb Fenbendazol in Dosierungen von 100 mg/kg und 4 × 50 mg/kg sowie Oxfendazol in Dosierungen von 50 mg/kg und 100 mg/kg erwiesen sich als unwirksam gegen 10 Wochen alte Rinderfinnen.

Comparative assessment of albendazole and triclabendazole ovicidal activity on Fasciola hepatica eggs

The benzimidazole compounds albendazole (ABZ) and triclabendazole (TCBZ) are both effective against Fasciola hepatica, although ABZ is only effective against adult flukes. Additionally, ABZ is a broad-spectrum nematodicidal compound with well-known ovicidal activity. However, no data on the ovicidal effect of TCBZ against F. hepatica eggs are available. The work reported here evaluated the comparative ovicidal effect of ABZ, TCBZ and their sulphoxide metabolites on F. hepatica eggs recovered from bile of sheep artificially infected with either a TCBZ-susceptible (Cullompton) or a TCBZ-resistant (Sligo) isolate of F. hepatica. Additionally, the effects of different non-flukicidal methylcarbamate benzimidazole compounds on the hatching of F. hepatica eggs were evaluated. Eggs (500 eggs/mL, n = 4) were incubated for 12 h either with TCBZ, TCBZ sulphoxide (TCBZ.SO), ABZ (5, 10 and 20 nmol/mL) or without drug (untreated control) (Experiment 1). Additionally, the effect of TCBZ and TCBZ.SO (5 nmol/mL) on egg hatchability was examined after a long (15 days) drug exposure (Experiment 2). Furthermore, the ovicidal effect of ABZ and ABZ.SO at different concentrations (5, 1, 0.5, 0.1and 0.05 nmol/mL) (Experiment 3), and the effect of fenbendazole (FBZ), oxfendazole (OFZ), mebendazole (MBZ), flubendazole (FLBZ) (5 nmol/mL) and reduced-FLBZ (R-FLBZ) (2 μg/mL) on fluke eggs, were evaluated after a 12-h exposure (Experiment 4). Egg hatch was assessed by direct microscopic observation after incubation at 25 °C for 15 days. TCBZ and TCBZ.SO did not affect egg hatch after a 12-h incubation. A similar result was obtained after a much longer drug exposure (15 days) (Experiment 1 and 2). However, a significant ( P < 0.05) inhibition of egg hatch was observed in ABZ- and ABZ.SO-incubated eggs (Experiments 1 and 3). Additionally, the non-flukicidal compounds (Experiment 4) affected egg hatchability, particularly FLBZ and R-FLBZ. In conclusion, ABZ and ABZ.SO had a clear inhibitory effect on egg development of F. hepatica. However, the most extensively used flukicidal compound, TCBZ, and its main sulphoxide metabolite, did not affect egg hatch, even in TCBZ-susceptible flukes.

Effect of Fenbendazole on Turkey Semen Quality

Fenbendazole (FBZ) is an anthelmintic recently approved to treat and control nematode infections in growing turkeys. When administered to growing turkeys there are no detrimental side effects. However, when we used FBZ to treat nematodes in mature breeder toms, we observed a decrease in semen quality and a subsequent precipitous decline in fertility to less than 20% within 6 wk of administration. An experiment was designed to determine the impact of FBZ administration on aspects of spermatogenesis and semen quality. We discovered that although sperm viability and concentration was not significantly affected by FBZ, this drug significantly reduced sperm mobility. However, normal mobility resumed within 6 wk after FBZ administration. Fenbendazole binds to tubulin and interferes with microtubule assembly. Based on testes histology and the immunocytochemical localization of tubulin in spermatids and mature sperm, FBZ had no affect on any aspect of spermatogenesis. We suggest that FBZ may be affecting sperm mobility by some molecular alteration of the sperm tail axoneme or midpiece, both of which are tubulin-containing structures. If a breeding flock of toms become infected with nematode parasites, a flock manager has the following options: do not treat the toms, find an alternative to FBZ, treat the toms with FBZ and increase the sperm number and frequency of artificial inseminations, or treat the toms with FBZ and secure semen from an uninfected tom flock.

Effect of fenbendazole and ivermectin on development of strongylate nematode eggs and larvae in calf feces

Thirty-nine weaned steer calves (mean weight 284kg) were maintained under dry-lot conditions and assigned (based on fecal nematode egg count) to one of three treatment groups of 13 animals each as follows: control (no treatment), fenbendazole (5mg kg −1, and ivermectin (0.2 mg kg −1). Fecal samples were collected 12 h before treatment, at treatment, and 12, 24, 48 and 72 h after treatment for determination of nematode eggs per gram, and (after culture) infective larvae per gram and population distribution. The effect of treatment on egg development was observed in feces collected 12 and 24 h after treatment. There was essentially no difference in efficacy, based on eggs counts, of fenbendazole and ivermectin. Egg count was reduced 100% by both anthelmintics at 72 h after treatment. Viability, based on percent of eggs reaching the infective larval stage, of developing stages at 12, 24, and 48 h after fenbendazole treatment was 0.1%, 1.1%, and 0%; after ivermectin treatment the corresponding values were 23.7%, 30.1%, and 28.6%, respectively. Fenbendazole treatment resulted in little or no development of eggs and/or larvae in feces deposited 12 and 24 h after treatment, whereas development proceeded normally (compared with the control group) in ivermectin treated feces. Population distribution of infective larvae was predominantly Haemonchus and Cooperia with some Ostertagia and Oesophagostomum.

Effect of fenbendazole on cow-calf performance and fecal egg counts (1985)

A field trial was conducted with 80 cow-calf pairs to evaluate the effect of deworming both cows and calves with fenbendazole, on cattle performance and internal parasite burden. Midseason and weaning weights of calves in the fenbendazole-treated group averaged 22.4 and 33.5 lb heavier (P<.04), respectively, than controls. Cow and calf fecal egg counts were low throughout the grazing season and were not materially affected by treatment.

Further observations on the action of fenbendazole against inhibited fourth stage larvae of Ostertagia ostertagi.

Two further trials are reported on the effect of fenbendazole on inhibited Ostertagia ostertagi larvae. In the first trial fenbendazole successfully eliminated inhibited burdens of O ostertagi, while in the second trial the effect was variable. As a result of these trials and previous reports it is concluded that a single oral dose of fenbendazole cannot be relied upon to prevent winter (type 2) ostertagiasis.

Fenbendazole against inhibited early-fourth-stageOstertagia ostertagiin cattle

Abstract Extract Sir — I am grateful for the opportunity to reply to the criticisms raised by Mr Vincent (5) . It seems to me that the bulk of his argument is concerned with the statistical treatment of the data that I presented (3) . However, he has apparently misunderstood the purpose of statistical analysis of results, and also seems to have missed the point of my paper. For example, he states that my results “are contradictory to all previous trials (sic) results”. My interpretation. arising from the method of analysis chosen, is that under the conditions of my trials, any apparent effect of fenbendazole could be due to chance.

The effect of fenbendazole in removing inhibited early-fourth-stageOstertagia ostertagifrom yearling cattle

Summary Fenbendazole had no significant effect on numbers of naturally-acquired, inhibited, early-fourth-stage Ostertagia ostertagi in 13- to 15-month-old steers. In six of the 12 animals dosed with this drug in two trials, total counts of O. ostertagi remaining exceeded 34 000, the highest being 108 000.

The effect of fenbendazole on nematode parasites in experimentally infected lambs.

Fenbendazole given orally to experimentally infected lambs at a dose rate of 5 mg per kg was found to be 100 per cent effective against three and 10-day larave and also against 20-day adults of H contortus, O circumcincta, N battus and T colubriformis. The same dose was also 100 per cent effective against 10-day, 17-day larvae and 27-day adult D filaria.