• YAKHAK HOEJI
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• v.20 no.1
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• pp.27-31
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• 1976

The stability of a newly introduced anthelmintic, mebendazole, in sweetened and aqueous suspension was tested by the accelerated temperature method and the effect of pH on the stability of mebendazole was studied. Mebendazole in aqueous and sweetened suspension was very stable at the pH range from 4 to 8.

• Parasites, Hosts and Diseases
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• v.59 no.3
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• pp.189-225
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• 2021

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.117-125
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• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

• Parasites, Hosts and Diseases
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• v.32 no.1
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• pp.49-52
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• 1994

Nine cases of human infection with Strongyloines stercornlis are reported among patients admitted to the Seoul Paik and Sang-Kye Paik Hospitals, Inje University, from April 1990 to Junuary 1992. The Patients, 7 males and 2 females acted between 50 and 70, either had the history of long term use of steroids for management of arthritis, or were complicated with other chronic diseases such as hypertension, liver diseases, psychotic disorders, and gastrointestinal problems. All of the nine patients revealed rhabditoid larvae of S. stercorolis in fecal examination. A 57-year-old woman who complained of arthritis and abdominal discomfort, was treated with albendazole and mebendazole, and on the 4th and 5th treatment day 220 parasitic adult females were collected from the diarrheal stool. The patient had a long history of administration of steroids for treatment of arthritis, and seems to have suffered from hyperinfection syndrome due to autoinfection with S. stercordis. This is the 3rd report on the recovery of parasitic adult females of S. stercoraLis in Korea.

• YAKHAK HOEJI
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• v.37 no.3
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• pp.216-227
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• 1993

Complex formations of practically insoluble antelmintic drugs such as mebendazole (MBZ), albendazole (ABZ) and flubendazole (FBZ) with dimethyl-$\beta$-cyclodextrin (DM-$\beta$-CyD) and 2-hydroxypropyl-$\beta$-cyclodextrin (HP-$\beta$-CyD) together with $\alpha$-, $\beta$- and $\gamma$-cyclodextrins(CyDs) in duffered solutions were investigated by solubility method. $A_{L}$ type phase solubility diagrams were obtained in all cases except for the complexation (B$_{s}$, type) of FBZ with $\gamma$-CyD. The highest stability constants were obtained with DM-$\beta$-CyD, followed by $\alpha$-CyD > $\beta$-CyD > HP-$\beta$-CyD > $\gamma$-CyD for ABZ, and HP-$\beta$-CyD > $\gamma$-CyD > $\beta$-CyD > $\alpha$-CyD for FBZ at pH 1.2. On the other hand, solid dispersion systems of ABZ and FBZ with $\beta$- and DM-$\beta$-CyDs were prepared by solvent evaporation method and evaluated by dissolution, differential thermal analysis and powder x-ray diffractometry. The dissolution rates of ABZ- and FBZ-DM-$\beta$-CyD solid dispersions were much faster than those of drugs alone, corresponding physical mixtures and tablets on market both at pH 1.2 and 6.8. Although dissolution rates of all samples at pH 6.8 were by far lower than those obtained at pH 1.2, as explained by pH-solubility profiles for ABZ and FBZ, the dissolution rates at pH 6.8 of ABZ from $\beta$- and DM-$\beta$-CyD solid dispersions exceeded the respective equilibrium solubility (23.9 $\mu\textrm{g}$/ml). Fast dissolution of ABZ from solid dispersions with CyDs was attributed to the reduction of drug crystallinity and particle size which was supported by DTA and powder x-ray diffractometry. Consequently these results suggest that solid dispersion systems with CyDs may provide useful means to markedly enhance the solubility and dissolution of benzimidazole antelmintic drugs.

• Parasites, Hosts and Diseases
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• v.21 no.1
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• pp.95-101
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• 1983

편층증의 개인치료와 집단관리에 있어서 메벤다졸의 유용성 및 효과를 측정하였다. 메벤다졸(100∼1,200mg) 투약 3주후 430명에 있어서의 치료효과는 15.0∼64.0% 및 24.6∼95.2%의 치유율 및 충란감소율을 보여 대체로 만족스럽지 못한 결과이었으나 메벤다졸의 총 투여량이 높으면 높을수록 치유율 및 충란감소율도 높아지는 것이 관찰되었다. 일정간격 반복투여(600mg용량)에 의한 집단관리를 주민(4개군, 총 551명)의 편충란양성율은 3개월간격(3일 분복군) 투여 군에서 가장 현저한 감소추세를 보여 관리시작후 1년만에 40.0%에서 5.6%로 저하되었고, 3개월 간격(단희 또는 2회 분복군), 6개월, 12개월군 및 대조군에서는 감소추세가 완만하거나 거의 관찰되지 않았다. 이상의 결과로 보아, 메벤다졸은 편충의 개인치료에는 그다지 우수한 결과를 나타내지 않았으나, 3개월간격으로 반복투여하면 집단관리에는 유효한 약제가 될 수 있을 것으로 생각되었다.

• Korean Journal of Veterinary Research
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• v.54 no.2
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• pp.127-129
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• 2014

A male, 3.5 month old Pomeranian dog was diagnosed with a natural infection of Crenosoma (C.) vulpis in Daejeon, Korea. First stage larvae of C. vulpis were detected by fecal examination using the Baermann technique. Thoracic radiographs revealed mild, pervasive bronchial infiltration of the lung. Enumeration of larvae via the McMaster technique revealed 1,600 larvae per gram of feces. The dog was treated with mebendazole, and clinical symptoms were resolved 2 weeks post-treatment, as indicated by the subject presenting fecal tests negative for C. vulpis.

• Parasites, Hosts and Diseases
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• v.23 no.1
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• pp.7-17
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• 1985

In order to determine the susceptible age of Enterobius vermicular is to anthelmintics and to observe the chronologie growth of female E. vermicularis in man, experimental infections were done. About 500 eggs were challenged to 19 volunteers. After 4, 8, 16, 20, 24, 28, 32 and 35 days of infection, each case was treated by either mebendazole or pyrantel pamoate. On the 40th day of infection all cases including control were treated again to terminate the experimental infection and to evaluate the effect of previous treatment. Each case collected 3-day stools to harvest the expelled worms. The results could be summarized as follows: 1. The infection rates of females were in range of 0.6~13.1 % in control cases. Because the collected worms showed comparable growth and development by day, the worms were concluded to be derived from experimental infection. 2. Cases that were treated with mebendazole on 4, 8 and 16 days after infection expelled 37.5%, 2.5% and 67.5% of the number expelled by a control case on the 40th day. Cases treated thereafter expelled no worms on the 40th day. 3. Cases that were treated with pyrantcl pamoates on 4, 8, 16, 24, 28, 32 and 35 days, expelled 90.7%, 25%, 45.3%, 8%, 2.7%, 5% and 29.3% of the number collected from control cases in respect. 4. All the worms collected were females. The total body length increased consistently and comparably from the 20th day of infection. Those collected on the 20th day were 2.5~3.0 mm long with vagina, sac-like structure and strands of ovaries; 24 day-old worms may have short uterus, 28 day-old worms had long uterus without eggs, 32 day-old worms began to produce eggs, 35 day-old worms showed wide variations in egg deposit in uterus, and 40 day-old worms had uterus filled with eggs from vulva to anal levels. From the above results, it was inferred that the life span of female Enterobius vermicularis was longer than 40 days, and the developmental stages of worms younger than 16 days resisted considerably to both mebendazole and pyrantel pamoate.

• Parasites, Hosts and Diseases
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• v.38 no.4
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• pp.267-273
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• 2000

We report 5 cases of ocular toxocariasis in Korean adults complaining of visual impairment along with floating or bubbling sensation. Fundoscopic examination revealed a retinal detachment along with exudate in 4 cases. They all showed typical reaction by ELISA and immunoblot against Toxocra excretory-secretory antigen. One case showed high level of anti-Toxocara IgE antibodies (34.000 Toxocara units/L) as well as increased level of serum total IgE antibodies and the specific IgE antibodies for 3 inhalant antigens, suggesting that high level of anti-Toxocara IgE antibodies was associated with an atopic status. Clinical manifestations were improved after the sequential use of steroids then mebendazole. We also suggest that ocular toxocariasis should be thoroughly investigated even when an evocative uniocular inflammatory lesion is encountered in peripheral retina without a systematic disease.