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.

Introduction: The cytotoxicity of anthelmintic agent, albendazole (ABZ) and its two major metabolites, sulfoxide (ABZSO) and sulfone (ABZ-SO2), on non-hepatic Balb/c 3T3 line, two hepatoma cell lines (FaO, HepG2), and isolated rat hepatocytes was investigated. Material and Methods: Cell cultures were exposed for 24, 48, and 72 h to eight concentrations of the compounds ranging from 0.05 to 100 μg/mL (ABZ) and from 0.78 to 100 μg/mL (ABZ-SO and ABZ-SO2). Three different assays were applied in which various biochemical endpoints were assessed: lysosomal activity - neutral red uptake (NRU) assay, proliferation - total protein contents (TPC) assay and lactate dehydrogenase (LDH) leakage assay. Results: The most toxic was albendazole whose EC50 values calculated from the concentration effect curves ranged from 0.2 to 0.5 μg/mL (Balb/c 3T3 ) and from 0.4 to 73.3 μg/mL (HepG2). Rat hepatoma line and isolated rat hepatocytes were less sensitive to the impact of ABZ. Toxic action expressed as EC50 was recorded after 72 h exposure only in LDH release assay at 0.8 μg/mL and 9.7 μg/mL respectively. The toxicity of metabolites was much lower. The most sensitive to ABZ-SO were fibroblasts and EC50-72h values were similar in all three assays used, i.e. NRU (14.1 μg/mL), TPC (15.8 μg/mL), and LDH (20.9 μg/mL). In the case of ABZ-SO2 the mean effective concentrations were the highest, and could be reached only in one LDH assay. These values (μg/mL) were as follows: 65.3 (FaO), 65.4 (HepG2), 75.8 (hepatocytes), and 77.4 (Balb/c 3T3). Conclusion: The differences in in vitro toxicity of albendazole depend on metabolic ability of the cellular models. Primary cultured rat hepatocytes represent a valuable tool to study the impact of biotransformation on the cytotoxicity of drugs.

The control of gastrointestinal nematodes (GINs) in small ruminants is principally dependent on anthelmintic therapy, which encounters the rising problem of anthelmintic resistance (AR) development. Veterinarians reported anthelmintic failure in several sheep farms in Arbat District, Sulaymaniyah, northern Iraq, which called for a systematic study about the efficacy of three commonly used drugs: albendazole, ivermectin, and levamisole.

Introduction: Albendazole is used to treat endoparasitic diseases in animals and humans. After oral administration, it is quickly oxidised into its pharmacologically active metabolite albendazole sulfoxide and then to sulfone. However, it is not clear which compound is responsible for toxic effects towards mammalian cells. Material and Methods: The model systems comprised cultures of isolated rat hepatocytes, two hepatoma cell lines (FaO, HepG2), and non-hepatic Balb/c 3T3 line. Cells were exposed for 24, 48, and 72 h to eight concentrations of albendazole ranging from 0.05 to 100 μg/mL. At all three time points cytotoxic effects were assessed by MTT assay and metabolites in the culture media were determined by LC-MS/MS analysis. Results: The effective concentrations EC50-72h showed that Balb/c 3T3 cells were the most sensitive to albendazole (0.2 ±0.1 μg/mL) followed by FaO (1.0 ±0.4 μg/mL), and HepG2 (6.4 ±0.1 μg/mL). In the case of isolated hepatocytes this value could not be attained up to the highest concentration used. Chemical analysis revealed that the concentrations of albendazole in hepatocytes and HepG2 and FaO culture media gradually decreased with incubation time, while the concentrations of its metabolites increased. The metabolism in isolated hepatocytes was dozens of times greater than in HepG2 and FaO cells. Two metabolites (albendazole sulfoxide, albendazole sulfone) were detected in isolated hepatocytes and HepG2 culture medium, one (albendazole sulfoxide) in FaO culture medium and none in Balb/c 3T3. Conclusion: The obtained data indicate that metabolism of albendazole leads to its detoxification. The lower cytotoxic potential of metabolites was confirmed in the independent experiments in this study.

Introduction: The cytotoxicity of anthelmintic agent, albendazole (ABZ) and its two major metabolites, sulfoxide (ABZSO) and sulfone (ABZ-SO₂), on non-hepatic Balb/c 3T3 line, two hepatoma cell lines (FaO, HepG2), and isolated rat hepatocytes was investigated. Material and Methods: Cell cultures were exposed for 24, 48, and 72 h to eight concentrations of the compounds ranging from 0.05 to 100 μg/mL (ABZ) and from 0.78 to 100 μg/mL (ABZ-SO and ABZ-SO₂). Three different assays were applied in which various biochemical endpoints were assessed: lysosomal activity - neutral red uptake (NRU) assay, proliferation - total protein contents (TPC) assay and lactate dehydrogenase (LDH) leakage assay. Results: The most toxic was albendazole whose EC₅₀ values calculated from the concentration effect curves ranged from 0.2 to 0.5 μg/mL (Balb/c 3T3) and from 0.4 to 73.3 μg/mL (HepG2). Rat hepatoma line and isolated rat hepatocytes were less sensitive to the impact of ABZ. Toxic action expressed as EC₅₀ was recorded after 72 h exposure only in LDH release assay at 0.8 μg/mL and 9.7 μg/mL respectively. The toxicity of metabolites was much lower. The most sensitive to ABZ-SO were fibroblasts and EC₅₀₋₇₂ₕ values were similar in all three assays used, i.e. NRU (14.1 μg/mL), TPC (15.8 μg/mL), and LDH (20.9 μg/mL). In the case of ABZ-SO₂ the mean effective concentrations were the highest, and could be reached only in one LDH assay. These values (μg/mL) were as follows: 65.3 (FaO), 65.4 (HepG2), 75.8 (hepatocytes), and 77.4 (Balb/c 3T3). Conclusion: The differences in in vitro toxicity of albendazole depend on metabolic ability of the cellular models. Primary cultured rat hepatocytes represent a valuable tool to study the impact of biotransformation on the cytotoxicity of drugs.

Efficacy of albendazole for treating giardiasis in dogs was assessed in 3 experiments. In experiment 1, Giardia cysts were cleared from feces of 5 of 7 dogs (as determined by the zinc-sulfate concentration technique) after the dogs received a single dose of albendazole (25 mg/kg of body weight, PO), whereas feces of 3 of 7 dogs became clear of cysts without treatment. In experiment 2, feces of 5 of 5 dogs became clear of cysts after albendazole treatment (25 mg/kg, PO, q 12 h for 4 doses); feces of 1 of 5 untreated control dogs became clear. In experiment 3, feces of 18 of 20 dogs became clear of cysts after albendazole 25 mg/kg, PO, q 12 h for 4 doses) was given; none of the 20 control dogs had feces clear of cysts. Signs of toxicosis were not observed in any dog. These results indicate that a single dose of albendazole (25 mg/kg, PO) is not effective for treating giardiasis in dogs. However, 4 doses of albendazole (25 mg/kg, PO, q 12 h) are highly effective and nontoxic for treatment of giardiasis in dogs.

Albendazole (10 mg(kg of body weight) was administered as a drench suspension or as a feed additive to 24 cattle with naturally acquired infections of Fasciola hepatica and Fascioloides magna. Cattle were euthanatized 16 to 30 days after treatment, and the number of viable flukes was counted. Viable F hepatica and F magna were decreased by 91.4% and 70.6% for drench administration and by 82.9% and 71.9% for the feed additive treatment, respectively. There was no significant difference between the efficacy of the 2 formulations in decreasing viable fluke numbers, compared with untreated controls.

To determine resistance of small strongyles to albendazole, 3 female ponies (group 1) were grazed on a pasture from May to November 1985 and were treated with 7.5 mg of albendazole/kg of body weight, PO, 2 days before turnout in May and again in June and in July. Three other female ponies (group 2) grazed on a similar pasture from May to July, were treated with 7.5 mg of albendazole/kg, and were removed to another pasture until November. In December, ponies from both groups were treated with 7.5 mg of albendazole/kg, and 8 days later, they were euthanatized and necropsied for a critical test. Worm egg counts in the ponies' feces revealed that the May treatment of group 1 and the July teatment of group 2 were more effective than were later treatments. Numbers of small strongyles were higher in group 1 than in group 2. Efficacy of treatment against all developmental stages of small strongyles were higher in group 2 than in group 1. Efficacy was low in both groups against parasitic 3rd- and 4th-stage larvae. Fifteen species of small strongyles were identified at necrospy. Efficacy was limited against adult Cyathostomum coronatum, Cya labratum, Cylicostephanus calicatus, and Cyl poculatus in both groups; Cylicocyclus nassatus, Cyl minutus, and Cyl longibursatus in group 1; and Cya labiatum in group 2. Efficacy was 100% against Cya catinatum, Cyl goldi, and 5 other species that were found in low numbers.

There are limited data on the efficacy of antiparasitic treatments and husbandry methods to control nematode infections in captive populations of African green monkeys (AGMs), Chlorocebus sabaeus. In faecal egg count (FEC) tests, 10 of the 11 (91%) adult male AGMs captured from the large feral population on the island of St Kitts had evidence of nematode infections, mostly Capillaria (8/11, 73%), Trichuris trichiura (7/11, 64%) and strongylid species (7/11, 64%) specifically (hookworm and Trichostrongylus, 50/50), but also Strongyloides fuelleborni (1/11, 9%). When kept in individual cages with cleaning and feeding regimens to prevent reinfections and treated concurrently with ivermectin (300 µg/kg, given subcutaneously) and albendazole (10 mg/kg, given orally) daily for 3 days, 60% (6/10) of the AGMs were negative at a follow-up FEC at 3 months and by FEC and necropsy at the end of the study 5-8 months later. One monkey appeared to have been reinfected with T. trichiura after being negative by FEC at 3 months post-treatment. Four AGMs were positive for T. trichiura at the 3 month FEC follow-up but were negative at the end of the study after one further treatment regimen. Although initially being cleared of Capillaria following treatment, three AGMs were found to be infected at the end of the study. The ivermectin and albendazole treatment regimen coupled with good husbandry practices to prevent reinfections effectively controlled nematode infections in captive AGMs.

Studies were undertaken to determine the efficacy of milbemycin oxime against the enteric adult stages of Trichinella spiralis and of albendazole against the muscle stage larvae in experimentally infected dogs and cats. Specific-pathogen-free Beagle pups (n = 6) and domestic shorthair kittens (n = 6) were inoculated with 7,500 first-stage larvae of Trichinella spiralis. Physical examination (including collection of blood and fecal samples) was performed weekly. During the first week after inoculation, all animals had mild gastrointestinal tract disturbances, but stages of T. spiralis were not observed in the feces. Beginning on postinoculation day (PID) 10, 3 pups and 3 kittens were treated with milbemycin oxime (1.25 mg/kg of body weight, PO, q 12 h) for 10 days. Muscle biopsy specimens were taken from dogs and cats on PID 26 and 29, respectively. Mean numbers of larvae per gram of muscle were 30.3 in the control and 37.7 in the treated dogs. Mean numbers of larvae per gram of muscle in the control and treated cats were 318.7 and 89.3, respectively. Two dogs and 2 cats were removed from the study at that time. The remaining animals, 2 each of the control and milbemycin oxime-treated animals, were given albendazole (50 mg/kg, PO, q 12 h) for 7 days starting at PID 31 and 34 in dogs and cats, respectively. Muscle biopsy specimens were again taken at PID 46 and 49, for dogs and cats, respectively; mean numbers of larvae recovered from muscle were 0.6 for dogs and 13.5 for cats.