BACKGROUND: During the last two decades, anthelmintic drugs have been increasingly applied against gastrointestinal parasites of sheep in Iran. OBJECTIVES: For this purpose, drug resistance to albendazole (Alb) and fenbendazole (Feb) in gastrointestinal nematodes in sheep of Saqez multiplicity was assessed. METHODS: In in-vivo experiment, a total number of 90 sheep in three groups (30 sheep/group) with EPG≤150 were examined for nematode resistance to Alb and Feb. They were treated with Alb and Feb or untreated (as a control group). RESULTS: There was significant difference between Alb and Feb treated groups and control group. The EPG in Alb, Feb and control groups was 59.8±1.93, 18.8±1.258 and 204.07±4.81, respectively. There was drug resistance against Alb in compassion with control group (R=71%). There was suspicion drug resistance for Feb in comparison with control group (R=90.66%). CONCLUSIONS: From the results of the present study, it was concluded that there was absolute and suspected drug resistance against Alb and Feb in sheep of Saqez municipality, Iran, respectively.

Objective: Solubility and bioavailability are crucial for maximizing the activity of an antiparasitic drug. This study aimed to develop a combined preparation for antiparasitic medicines using iver¬mectin (Iver), fenbendazole (FBZ), and triclabendazole (TBZ), considering their solubility, bioavail¬ability, and activity. Materials and Methods: Innovative preparations in solid dispersions (SD) were obtained using the joint mechanical processing of drug substances with polyvinylpyrrolidone (PVP) in an LE-101 roller mill. The preparations efficacy was studied in 140 sheep spontaneously infected with gastroin¬testinal Strongylata, Dicrococelium dendriticum, Moniezia expansa, and Melophagus ovinus. The preparations were given individually to the sheep in the form of an aqueous suspension orally. Their effectiveness was evaluated using intravital and postmortem parasitological examinations. Results: The results confirmed the increase in solubility of substances by 1329 times. The exper¬iments have shown the high efficacy of SD composition of FBZ/Iver/PVP (1/1/9) containing FBZ (at 3.0 mg/kg b/w) and Iver (at 0.2 mg/kg b/w) when used against gastrointestinal Strongylates and M. expansa (95.8% and 100%, respectively), to a lesser extent against M. ovinus (38.5%). The SD composition of TBZ/Iver/PVP (1/1/9) of TBZ (at 3.0 mg/kg b/w) and Iver (at 0.2 mg/kg b/w) showed a high efficacy against gastrointestinal Strongylata and D. dendriticum (96.8% and 100%, respectively) and less activity against M. ovinus (61.6%). Conclusion: The high parasiticidal activity of SD based on FBZ, TBZ, and Iver in comparison with initial substances is explained by the formation of inclusion complexes of these substances with PVP when SD is dissolved in water and the synergistic effect of the active substances of the prepa¬rations. The resulting complexes have increased solubility in water and bioavailability. The use of such an SD suggests a significant reduction in the dosages of FBZ and TBZ without losing parasit¬icidal activity. [J Adv Vet Anim Res 2020; 7(4.000): 718-725]

Objective: The purpose of our research was to evaluate the effect of mechanochemical technology on the efficacy of supramolecular complex of fenbendazole (SMCF) with polyvinylpyrrolidone (PVP) polymer against some helminthosis of animals.Materials and Methods: The SMCF samples with PVP were synthesized using a solid-state mechanochemical technology in activators of impact-abrading type and their physicochemical properties were analyzed. The efficacy of SMCF was studied on the laboratory model of Hymenolepis nana and Trichinella spiralis infection of mice and helminthosis of sheep.Results: In the trials conducted on laboratory models, the supramolecular complex showed 93.94% and 98.56 % efficacy at the dose of 1 mg/kg of body weight (b/w), while the substance of fenbendazole showed 7.97% and 8.33% efficacy at the same dose. A high efficacy (>94%) of the SMCF was revealed at the dose of 2.0 mg/kg of b/w at oral administration against nematodes in naturally infected sheep by the results of the fecal examination, while the substance of fenbendazole was active at the dose of 5.0 mg/kg at single oral administration. Moreover, the SMCF demonstrated 97.37% efficacy at the dose of 2 mg/kg against Moniezia spp. infection of sheep. Physicochemical studies confirmed the increase in solubility of the complex, reducing of particle sizes, amorphization of fenbendazole substance, and incorporating it with micelles of PVP.Conclusion: According to the results, supramolecular complex of fenbendazole with PVP was more active than the basic substance of fenbendazole and its anthelmintic properties were expanded. [J Adv Vet Anim Res 2019; 6(1.000): 133-141]

Fenbendazole (FBZ) is a benzimidazole anthelmintic widely used to treat parasitic infections. The anticancer effect of FBZ has been recently highlighted leading to its consideration as a potential anticancer agent. Although previous studies have demonstrated the effect of FBZ on cancer cells, there is a paucity of studies on the effect of FBZ on lymphoma cells and normal immune cells. Herein, we investigated the effects of FBZ on a mouse lymphoma cell line, EL-4 cells, and spleen cells, using vincristine as a positive control. The cellular metabolic activity of EL-4 cells was decreased by FBZ, but that of the spleen cells was not decreased. Moreover, FBZ reduced the mitochondrial membrane potential and induced reactive oxygen species production in EL-4 cells, but not in spleen cells. FBZ induced G2/M phase arrest and increased the sub G0/G1 phase ratio, indicating apoptosis. Furthermore, compared to the control cells, the reactivity of spleen cells pretreated with FBZ to lipopolysaccharide was maintained. In summary, FBZ is cytotoxic to EL-4 cells, but not to spleen cells. This study provides experimental evidence that FBZ exerts an anticancer effect, and less cytotoxic effects and functional damage to normal spleen cells.

Fenbendazole (FBZ) is a commonly used anthelmintic in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. FBZ can play a role as an anthelmintic and anticancer agent and an anti-inflammatory agent.

Ten controlled tests were done between 1972 and 1989, in lambs on pasture, evaluating activity of fenbendazole (FBZ; 5 mg/kg of body weight), oxfendazole (OFZ; 3.5 and 10 mg/kg), oxibendazole (OBZ; 10 mg/kg), pyrantel pamoate (PRT; 25 mg of base/kg), and thiabendazole (TBZ; 44 and 50 mg/kg) against natural infections of helminths, with emphasis on 2 strains (A and B) of Haemonchus contortus. Strain A was phenothiazine-susceptible and strain B was phenothiazine-resistant when isolated in 1955. For approximately 10 years prior to these tests, sheep infected with both strains had been treated periodically each year with several compounds, including thiabendazole, which was used many more times than the other drugs. For this study, 4 (FBZ, OFZ, OBZ, and PRT) of the 5 compounds were evaluated in either 1 or 2 controlled tests. The fifth compound, TBZ, was used for 5 tests. Strain A H contortus was resistant to TBZ for all years tested, but more susceptible to FBZ, OFZ, OBZ, and PRT. Overall, strain B was susceptible to TBZ (with a few exceptions), and also to FBZ, OFZ, OBZ (activity less on immature forms), and PRT. Other abomasal parasites (2 species of Ostertagia and 3 of Trichostrongylus) were found in low numbers, but removal overall was good for the compounds tested. Trichostrongylus axei, found in higher numbers than species of Ostertagia and other species of Trichostrongylus, were effectively removed by all compounds in most cases. Activities of TBZ and PRT were also evaluated against several species of intestinal helminths, most of which were found in low numbers. Cooperia curticei were inconsistently removed by TBZ, but activity of PRT was effective. Both compounds were active on mature Nematodirus spathiger, but TBZ had variable activity on immature forms. Strongyloides papillosus were effectively removed by TBZ. Other parasites found in lower numbers than the aforementioned 3 species were Capillaria spp, Trichuris spp, and Oesophagostomum columbianum; removal was variable for both drugs.

The efficacy, safety, and compatibility of fenbendazole (FBZ) and clorsulon (CLN) were tested after oral administration of label recommended and of higher (5 x) dosage rates to calves naturally infected with gastrointestinal nematodes and Fasciola hepatica. Results for 42 calves allotted to 4 treatment groups indicated a similar efficacy against mature F hepatica by FBZ (5 mg/kg of body weight) and CLN (7 mg/kg) in a combined oral suspension, compared with CLN (7 mg/kg) alone (100 vs 99% reduction). A lesser efficacy was observed against immature flukes (88.6 and 84.9% reduction, respectively). Calves given 25 mg of FBZ/kg and 35 mg of CLN/kg had nearly complete reduction of both mature (99.6%) and immature flukes (99.1%). Fasciola egg counts were reduced by > 99.5% in all treated groups. Against Ostertagia ostertagi, the percentage of efficacy of the combined FBZ (5 mg/kg) and CLN (7 mg/kg) treatment was 94.3% against adults and 81.3% against inhibited larvae. Efficacy against all other nematodes was 100%, except against Cooperia spp adults (98.3%) and immature Oesaphagostomum radiatum (88.0%). At 5 x dosage rates for FBZ and CLN, percentage of removal of adults and inhibited larvae of O ostertagi was 99.3 and 99.0%, respectively, and 99 to 100% for other nematodes. Results indicate that FBZ and CLN are compatible when mixed together and administered as an oral suspension to cattle and that the efficacy is similar to that of the drugs individually. On the basis of further results, we suggest that summer treatment may be superior in preventive value for gastrointestinal nematodes and F hepatica, compared with spring treatment, because of seasonal infection dynamics of the major cattle parasites in Louisiana.

The possible development of type-1 hypersensitivity reactions in the abomasal mucosa caused by soluble L3 products of Ostertagia ostertagi was studied in 4-month-old calves sensitized by repeated exposure to L3 over a 50-day period followed by anthelmintic treatment. Four groups each of 4 calves were used. Group 1 served as nonsensitized controls and group 2 as sensitized controls, group 3 was challenge exposed at 2-week intervals beginning at week 10 with a soluble L3 product (OAG), and group 4 was challenge exposed at 2-week intervals with an oral dose of L3, followed by anthelmintic treatment 3 days later. All calves infected with L3 became sensitized, as indicated by a positive reaction to an intradermal skin test. However, a passive cutaneous anaphylaxis was only partly effective in indicating the presence of homocytotropic antibody in the infected calves. Sensitized calves had significantly (P < 0.05) higher eosinophil counts and plasma pepsinogen values for the entire 14 weeks than uninfected controls. Globule leukocyte and mast cell counts from the abomasal mucosa were also significantly (P < 0.05) higher. Studies for possible immunomodulation revealed that lymphocyte counts decreased between every 2-week challenge-exposure period for groups-3 and -4 calves. A transient depression of blood lymphocyte (BL) responses to phytohemagglutinin (PHA), a T-cell mitogen, was observed over the first 8 weeks in the infected calves. Increases in BL responses to OAG were also observed. Differences were not observed in BL responses to pokeweed mitogen, a T- and B-cell mitogen. Blood lymphocyte responses to PHA in group-3 calves were low following the initial challenge exposure with OAG. The sensitized calf lymphocytes did not have suppressive activity on the response of control calf lymphocytes to PHA. Differences were not observed in lymphocyte responses to PHA in a suppressive assay done on abomasal lymph node lymphocytes. Increases in abomasal lymph node mass and lymphocyte responses to PHA, pokeweed mitogen, and OAG were observed in all sensitized calves. Histologic examination of abomasal lymph node sections from challenge-exposed calves revealed increased mitotic activity in germinal centers. Plasma pepsinogen values in groups 3 and 4 increased between each challenge exposure, which further suggested that type-1 hypersensitivity reactions had occurred in the abomasal mucosa, resulting in increased permeability and leakage of macromolecules.

Moniezia sp. in naturally infected calves on pasture, fenbendazole efficacy at three dosage levels: Georgia

fenbendazole safety tested in pigs, significant gross or histopathologic lesions not found