• Journal of Veterinary Science
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• 제21권5호
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• pp.72.1-72.10
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• 2020

Background: Fenbendazole, a dewormer drug, is used widely in the clinical treatment of parasite infections in animals. Recent studies have shown that fenbendazole has substantial effects on tumor growth, immune responses, and inflammatory responses, suggesting that fenbendazole is a pluripotent drug. Nevertheless, the antiviral effects have not been reported. Fenbendazole can disrupt microtubules, which are essential for multiple viruses infections, suggesting that fenbendazole might have antiviral effects. Objectives: This study examined whether fenbendazole could inhibit bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures. Methods: The effects of fenbendazole on viral production, transcription of the immediate early (IE) genes, viron-associated protein expression, and the cellular signaling PLC-γ1/Akt pathway were assessed using distinct methods. Results: Fenbendazole could inhibit BoHV-1 productive infections significantly in MDBK cells in a dose-dependent manner. A time-of-addition assay indicated that fenbendazole affected both the early and late stages in the virus replication cycles. The transcription of IE genes, including BoHV-1 infected cell protein 0 (bICP0), bICP4, and bICP22, as well as the synthesis of viron-associated proteins, were disrupted differentially by the fenbendazole treatment. The treatment did not affect the cellular signaling pathway of PLC-γ1/Akt, a known cascade playing important roles in virus infection. Conclusions: Overall, fenbendazole has antiviral effects on BoHV-1 replication.

• Environmental Analysis Health and Toxicology
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• 제25권3호
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• pp.197-205
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• 2010

The ecotoxicological effects of two antibiotics, fenbendazole and lincomycin, were observed in the harpacticoid copepod Tigriopus japonicus s.l. collected from tidal pools in the southern coast of Korea. Fenbendazole had a significant effect on the survival rates (p < 0.05), delay of copepodite emergence, and urosome size (p < 0.05). Lincomycin, on the other hand, had no significant influence on these environmental indicators. However, our analysis of morphological abnormalities in T. japonicus s.l. showed that lincomycin was more effective than fenbendazole in causing deformities. The pattern of deformity was diverse, with fused segments, and loss or addition of setae in the swimming legs. All of these patterns appeared as a result of relatively low concentrations of this antibiotic (0.3, $1\;{\mu}g\;L^{-1}$). We report here patterns of morphological abnormality in T. japonicus s.l. exposed to antibiotics, and suggest their possible application in ecotoxicological monitoring.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.377-387
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• 2022

Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracil-resistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.

• Environmental Analysis Health and Toxicology
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• 제24권4호
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• pp.311-320
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• 2009

The short term (24-hr) and long term (21 days) effects of copper, cadmium, fenbendazole and sulfathiazole on the survival of the Korean fairy shrimp Branchinella kugenumaensis were evaluated. The 24-hr median lethal concentrations ($LC_{50}$) of copper, cadmium, fenbendazole, and sulfathiazole were 39, 512, 182, and 31,818 ${\mu}g/L$, respectively. The toxicity of copper is highest among 4 chemicals used in this study, while sulfathazole the lowest. After the long term (21 days) exposure experiment, the $LC_{50}$ copper, cadmium, fenbendazole, and sulfathiazole were 1.12, 2.1, 0.1, 6.6 ${\mu}g/L$, respectively. The long term effects of antibiotics were highly enhanced while the short-term effects were not strong. The sensitivities of B. kugenumaensis to copper and cadmium were higher than or comparable to those of other freshwater branchiopods (Streptocephalus spp., Thamnocephalus sp.), and far higher than the marine species (Artemia sp.). There were significant effects on the survival of B. kugenumaensis after long term exposure to relatively lower concentrations of copper, cadmium, fenbendazole and sulfathiazole. Therefore, B. kugenumaensis seems quite a good candidate species for the ecotoxicological assessments of freshwater environments.

• 한국임상수의학회지
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• 제22권3호
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• pp.239-243
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• 2005

Current treatments for canine Giardia infections include albendazole, fenbendazole and metronidazole in the most cases. To compare efficacy of these antimicrobial drugs for treating naturally infected giardiasis in dogs, we used the zinc sulfate concentration technique(ZSCT) to figure out naturally infected with Giardia. In this study, feces were collected from 150 asymptomatic dogs at a kennel, 28 asymptomatic Giardia infected dogs were used by the allocated four group to receive albendazole(group A, 25 mg/kg, PO, bid, 7 days), fenbendazole(group F, 50 mg/kg, PO, sid, 7 days), metronidazole (group M, 50 mg/kg, PO, sid, 7 days), nontreated control(group NC) respectively. Fecal samples from each dog were examined for Giardia cysts within 3 days of the last treatment. Giardia cysts were not detected in the feces of any dog in group F. Cysts were detected in the feces 1 of 7 dogs in group A or in the feces 2 of 7 dogs in group M. In the group NC, cysts were detected in the feces of 7 of 7 dogs. Finally, there was significant difference for efficacy between antimicrobial drugs against Giardia in dogs. Fenbendazo1e is the most efficacy to have giardiacidal activity.

• 한국식품과학회지
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• 제42권5호
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• pp.515-520
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• 2010

본 연구를 통하여 확립된 시험법은 고감도를 가지고 선택성이 뛰어난 LC/MS/MS를 이용하여 한번의 시료전처리와 분석을 통하여 축산식품 중 잔류하는 벤지미다졸계 구충제인 albendazole, fenbendazole, thiabendazole, flubendazole 및 oxibendazole 5종의 잔류량 분석을 가능하게 하였다. 추출용매로 ethyl acetate를 사용하고 MCX 카트리지를 이용하여 정제를 한 시험법으로 Codex guideline(20)에 따라 검량선의 직선성, 회수율, 검출한계 및 정량 한계 등에 대한 실효성을 검증한 결과 검량선은 모두 0.999 이상의 좋은 직선성을 가졌으며 회수율은 albendazole 71-74%, fenbendazole 70-72%, thiabendazole 79-83%, flubendazole 79-83%, oxibendazole 81-86%로 좋은 결과를 얻었다. 또한 검출한계 및 정량한계는 0.01 ppb, 0.03 ppb로 잔류허용기준이 가장 낮은 flubendazole의 10 ppb보다 100배 정도 더 좋은 감도를 가지고 있으며, 소의 근육, 간, 및 천엽에서 MSPD법으로 분석한 실험(21)과 정제과정 없이 유기용매로 추출하여 LC/MS로 분석한 실험의 회수율(22)보다 본 연구의 시험법이 더 좋은 회수율을 보여주었다. 또한 확립된 시험법을 이용하여 유통 중인 돼지고기, 쇠고기, 닭고기 총 270건을 수거하여 잔류량을 모니터링 한 결과 경기, 충청, 전라, 경상 지역에서 수거한 돼지고기에서 fenbendazole이 0.0012-0.0031 mg/kg의 수치로 검출이 되었고, 그 검출률은 4.4%이었으나 잔류허용기준인 0.1 mg/kg보다 낮은 수준이었다. 또한 fenbendazole에 대한 노출량 평가 결과 JECFA에서 정하고 있는 ADI의 0.01% 이하로 나타났다. 그러나 축산 농가에서 축산물의 생산량을 높이기 위하여 벤지미다졸계 구충제를 과다 사용하거나 안전 휴약기간을 준수하지 않을 경우 축산물의 체내에 잔류가능성이 높기 때문에 지속적인 잔류실태 조사가 수행되어야 할 것으로 사료된다.

• 대한수의학회지
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• 제60권2호
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• pp.79-83
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• 2020

Fenbendazole (FBZ) is a benzimidazole anthelmintic that has been widely used in treatments for gastrointestinal parasites including pinworms and roundworms in animals. Recently, some studies demonstrated that FBZ has anti-cancer effects related to disruption of microtubule polymerization. In this study, we investigated whether FBZ has anti-cancer activity in HL-60 cells, a human leukemia cell line, and assessed its relationship with the production of reactive oxygen species (ROS). FBZ treatment at 0.25-1 μM significantly decreased the metabolic activity of HL-60 cells. The mitochondrial membrane potential of FBZ-treated HL-60 cells decreased in a concentration-dependent manner. Apoptosis analysis using annexin V-FITC/propidium iodide staining demonstrated that 1 μM FBZ increased the percentages of cells in apoptosis and necrosis. In addition, Hoechst 33342 staining showed the presence of broken nuclei in HL-60 cells treated with 0.5 and 1 μM FBZ. To investigate the anti-cancer mechanism of FBZ, HL-60 cells were treated with FBZ in the absence or presence of N-acetyl cysteine (NAC), an inhibitor of ROS production. NAC significantly recovered the decreased metabolic activity of HL-60 induced by 0.5 and 1 μM FBZ treatments. This study provides evidence that FBZ has anti-cancer activity in HL-60 cells provided, in part, via ROS production.

• 대한수의학회지
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• 제61권3호
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• pp.22.1-22.7
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• 2021

Fenbendazole (FBZ) is a commonly used anthelmintics 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. In addition to anthelmintic and anticancer agent, FBZ can play a role as an anti-inflammatory agent.

• 한국임상수의학회지
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• 제32권2호
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• pp.212-214
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• 2015

토끼에서 뇌포자육충증은 Encephalitozoon(E.) cuniculi에 의해 유발되는 전염성 질환이다. E.cuniculi는 숙주영역이 상당히 넓으며, 특히 면역능이 저하된 사람에서 기회 감염을 유발하기도 한다. 본 증례 보고에서 4 마리의 토끼가 사경과 안구진탕 증상으로 내원하였으며, 각 개체의 채혈을 통해 ELISA 검사를 수행하여 E.cuniculi에 양성임을 확인하였다. 토끼들은 fenbendazole로 4 주간 치료를 실시하였고, 치료효과는 신경증상의 발현정도에 따라 평가하였다. 치료한 네 마리 토끼 중 세 마리의 토끼에서 치료 3-5일 후부터 증상이 상당히 개선되었으나, 한 마리는 식욕부진과 사경증상이 개선되지 않고 치료 후 10일째 폐사하였다. 본 증례보고는 뇌포자육충 감염 애완토끼에 대한 fenbendazole의 치료효과를 규명한 최초의 보고이며, 본 증례를 통하여 애완토끼가 사람과 동물에 있어서 잠재적 E. cuniculi 보균동물로 인식되므로 이에 대한 주의를 필요로 한다.

• 분석과학
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• 제23권6호
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• pp.572-578
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• 2010

본 연구에서는 하천수 중 6종의 의약물질(cephradine, cefadroxil, penicillin G, vancomycin, iopromide, and fenbendazole)에 대한 전처리법과 분석 방법을 확립하였다. 하천수 중의 분석물질을 HLB(Hydrophilic-Lipophilic Balanced) 카트리지를 사용하여 추출/정제 및 농축하였다. HPLC/ESI-MS/MS를 이용하여 6종의 물질들을 동시에 분석하였다. Fenbendazole을 제외한 의약물질은 71.1~92.6% 범위의 양호한 회수율을 나타내었고, 상대표준편차는 11.2% 이하로 나타났다. 정량분석을 위해서 0.007~1.2 ng/mL 범위에서 $r^2$=0.99 이상의 높은 직선성을 나타내는 검량선을 얻었다. 검출한계(LOD)와 정량한계(LOQ)는 각각 7.2~128.7 pg/mL, 23.8~429.1 pg/mL로 나타났다. 이 분석 방법은 하천수 중 의약품에 대한 모니터링에 유용하며, 하천수 중 iopromide과 fenbendazole은 높은 농도로 검출되었다.