Abstract
The direct cytotoxicity of mebendazole (MBZ) was investigated by using cell lines derived from human, mouse and rat liver. It was demonstrated that Chang liver cells (derived from human liver) were more sensitive to the cytotoxic effects of MBZ than the other two cell lines. Longer incubation of the cells with MBZ resulted in stronger toxicity, and the cytotoxicity was dependent on the MBZ concentration above a certain threshold value (0.25–0.50 mg/l in a 42-h culture). Inhibition of the proliferation of Chang liver cells by MBZ was detected at a concentration of 0.008 mg/l, a lower concentration than that having a cytotoxic effect. The other two cell lines were less sensitive to the inhibitory effect of MBZ. Proliferation of human mononuclear cells following stimulation by phytohemagglutinin (PHA) was inhibited by MBZ, and this inhibition was more extensive than that of cells stimulated with whole formalin-treatedPseudomonas aeruginosa. It is suggested that dividing cells may be more sensitive to MBZ cytotoxicity. This anti-proliferative effect may be related to its clinically known side effects, such as hepatotoxicity and bone marrow suppression.
This is a preview of subscription content, log in via an institution to check access.
References
Bekhti A, Piprtte J (1987) Hepatotoxicity of mebendazole. Relationship with serum concentrations of the drug. Gastroenterol Clin Biol 11: 701–703
Braithwaite PA, Roberts MS, Allan RJ, Watson TR (1982) Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease. Eur J Clin Pharmacol 22: 161–169
Davis A, Pawlowski ZS, Dixon H (1986) Multicentre clinical trials of benzimidazolecarbamates in human echinococcosis. Bull WHO 64: 383–388
Grove DI (1982)Strongyloides ratti andS. stercoralis: the effects of thiabendazole, mebendazole and cambendazole in infected mice. Am J Trop Med Hyg 31: 469–476
Grove DI (1989) Treatment. In: Grove DI ed. Strongyloidiasis: a major roundworm infection of man. Taylor & Francis, London, pp 199–231
Harris A (1979) Pyrexia and mebendazole. BMJ 2: 1365
Hoegaerden MV, Ivanoff B (1987) The use of mebendazole in the treatment of filariases due toLoa Loa andMansonella perstans. Ann Trop Med Parasitol 81: 275–282
Horstmann RD, Kern P, Volkmert KJ, Dietrich M (1982) Observations on mebendazole vs. thiabendazole in the treatment of human trichinellosis. Tropenmed Parasit 33: 191–194
Libova E, Mittermayer T, Bayer A, Chroust K, Sucharova T, Chudora M (1984) Epidemy of human trichinellosis in Bordejov region in 1980. Helminthologia 21: 81–91
Luder PJ, Siffert B, Witassek F, Meister F, Bircher J (1986) Treatment of Hydatid disease with high oral doses of mebendazole Long-term follow up of plasma mebendazole levels and drug interactions. Eur J Clin Pharmacol 31: 443–448
Marsboom R (1973) Toxicologic studies on mebendazole. Toxicol Appl Pharmacol 24: 371–377
Michiels M, Hendriks R, Heykants J (1982) The pharmacokinetics of mebendazole and flubendazole in animals and man. Arch Int Pharmacodyn Ther 256: 180–191
Mravak S, Schopp W, Bienzle U (1983) Treatment of strongyloidiasis with mebendazole. Acta Trop 40: 93–94
Munst GJ, Karlaganis G, Bircher J (1980) Plasma concentration of mebendazole during treatment of echinococcosis. Preliminary results. Eur J Clin Pharmacol 17: 375–378
Murray-Lyon IM, Reynolds KW (1979) Complications of mebendazole treatment for hydatid disease. BMJ 2: 1111–1112
Musgrave IA, Hawes RB, Jameson JL, Sloane RA, Quayle PA (1979) Mebendazole. Evaluation of a new antihelminthic for trichuriasis, hookworm and strongyloidiasis. Med J Aust 1: 403–405
Seitz R, Schwerk W, Arnold R (1983) Hepatozellulare Arzneimittelreaktion unter Mebendazoltherapie bei Echinococcus cysticus. Z Gastroenterol 21: 324–329
Shikiya K, Kuniyoshi T, Higashionna A, Arakaki T, Oyakawa T, Kadena K, Kinjo F, Saito A, Asato R (1990) Treatment of strongyloidiasis with mebendazole and its combination with thiabendazole. J Jpn Assoc Infect Dis 64: 1408–1415 (English abstract)
Van den Bossche H (1972) Biochemical effects of the anthelmintic drug mebendazole. In: Van den Bossche H (ed) Comparative biochemistry of parasites. Academic Press, New York and London, pp 139–157
Van den Bossche H (1982) Mebendazole and related anthelmintics. Adv Pharmacol Chemother 19: 67–128
Witassek F, Bircher J (1983) Chemotherapy of larval echinococcosis with mebendazole: microsomal liver function and cholestasis as determinants of plasma drug level. Eur J Clin Pharmacol 25: 85–90
Woodtli W, Bircher J, Witassek F, Eckert J, Wuthrich B, Ammann RW (1985) Effect of plasma mebendazole concentrations in the treatment of human echinococcosis. Am J Trop Med Hyg 34: 754–760
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Higa, F., Kitsukawa, K., Gaja, M. et al. Cytotoxicity of mebendazole against established cell lines from the human, rat, and mouse liver. Arch Toxicol 66, 224–227 (1992). https://doi.org/10.1007/BF01974020
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01974020