Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes
- 91 Downloads
The in vitro biological oxidation of albendazole to albendazole sulfoxide by rat liver microsomes has been studied. This reaction corresponds to a NADPH-dependent enzymatic system, characterised by Km and Vm values of 53.6 μM and 0.59 nmole/mg protein per min.
The rate of sulfoxidation by liver microsomes of rats treated with phenobarbital, B-naphthoflavone, Aroclor 1254 and 3-methylcholanthrene was not increased. SKF 525A and metyrapone did not inhibit albendazole sulfoxidase.
Thiobenzamide and tranylcypromine decreased sulfoxidation to 48 and 52% of control values. The inhibition by tranylcypromine was competitive. Purified flavin adenine dinucleotide (FAD)-containing monooxygenase from hog liver microsomes catalysed sulfoxidation of albendazole (V=0.52 nmole/nmole enzyme per min).
The present data demonstrate that sulfoxidation of albendazole in the rat liver is not catalysed by a cytochrome P450-dependent monooxygenase and suggest that albendazole is a substrate for FAD-containing monooxygenase (FMO).
KeywordsSulfoxide Phenobarbital Liver Microsome Flavin Albendazole
Unable to display preview. Download preview PDF.
- Aitio, A., 1978. A simple and sensitive assay of 7-ethoxycoumarin deethylation. Anal. Biochem., 85: 488–491.Google Scholar
- Cashman, J.R. and Hanzlik, R.P., 1981. Microsomal oxidation of thiobenzamide, a photometric assay for the flavin containing monooxygenase. Biochem. Biophys. Res. Commun., 98: 147–153.Google Scholar
- Delatour, P., Garnier, F., Benoit, E. and Longin Ch., 1984. A correlation of toxicity of albendazole and oxfendazole with their free metabolites and bound residues. J. Vet. Pharmacol. Therap., 7: 139–145.Google Scholar
- Douch, P.G.C., and Buchanan, L.L., 1979. Some properties of the sulfoxidases and sulfoxide reductases of the cestode Moniezia expansa, the nematode Ascaris suum and mouse liver. Xenobiotica, 9: 675–679.Google Scholar
- Guengerich, F.P., Dannan, G.A., Wright, S.T., Martin, M.V. and Kaminsky, L.S., 1982. Purification and characterization of liver microsomal cytochromes P450: electrophoretic, spectral catalytic, and immunochemical properties and inducibility of eight isoenzymes isolated from rats treated with phenobarbital or B-naphthoflavone. Biochemistry, 21: 6019–6030.Google Scholar
- Gyurik, R.J., Chow, A.W., Zaber, B., Bruner, E.L., Miller, J.A., Villani, A.J. Petka, L.A. and Parish, R.C., 1981. Metabolism of albendazole in cattle, sheep, rats and mice. Drug Met. Disp., 19: 503–508.Google Scholar
- Hajjar, N.P. and Hodgson, E., 1980. Flavine adenine dinucleotide dependent monoxygenase: its role in the sulfoxidation of pesticides in mammals. Science, 209: 1134–1136.Google Scholar
- Hajjar, N.P. and Hodgson, E., 1982. Sulfoxidation of thioether containing pesticides by the flavin adenine dinucleotide dependent monooxygenase of pig liver microsomes. Biochem. Pharmacol., 31: 745–752.Google Scholar
- Hodgson, E., 1982–1983. Production of pesticide metabolites by oxidative reactions. J. Toxicol., 19 (6–7): 609–621.Google Scholar
- Kahl, G.N. and Netter, K.J., 1970. The effect of metyrapone on cellular respiration and microsomal drug oxidation. Biochem. Pharmacol., 19: 27–34.Google Scholar
- Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193: 265–275.Google Scholar
- Marriner, S.E., Bogan, J.A. and Vandaele, W., 1981. Comparison of the pharmacokinetics of albendazole and its major metabolites after oral administration of albendazole as a suspension and as a paste formulation to sheep. Zentrabl. Veterinaermed. Reihe B., 28: 19–26.Google Scholar
- Mazel, P., 1972. Experiment illustrating drug metabolism in vitro. In: V.N. Ladu, H.G. Mandel and E.L. Ways (Editors), Fundamentals of drug metabolism and drug disposition. Williams and Wilkins, Baltimore, pp. 546–582.Google Scholar
- Omura, T. and Sato, R., 1964. The carbon monoxide binding pigment of liver microsomes. Evidence for its hematoprotein nature. J. Biol. Chem., 239: 2370–2378.Google Scholar
- Penicaut, B., Maugein, P.H., Maisonneuve, H. and Rossignol, J.F., 1983. Pharmacocinétique et métabolisme urinaire de l'albendazole chez l'home. Bull. Soc. Path. Ex., 76: 698–708.Google Scholar
- Poulsen, L.L., 1981. Organic sulfur substrates for the microsomal flavin containing monooxygenase. Rev. Biochem. Toxicol., 3: 33–49.Google Scholar
- Schenkman, S.B., Remmer, H. and Estabrook, R.W., 1967. Spectral studies of drug interaction with hepatic microsomal cytochrome. Molecular Pharmacology, 3: 113–123.Google Scholar
- Testa, B., 1980. Inhibition du métabolisme des médicaments et impacts thérapeutiques. Actualités de Chimie Thérapeutique, 7: 87–145.Google Scholar
- Theodorides, V.J., Gyurik, R.J., Kingsbury, W.D. and Parish, R.C., 1976. Anthelmintic activity of albendazole against liver flukes, tapeworms lung and gastrointestinal roundworms. Experientia, 32: 702–703.Google Scholar
- Tynes, R.E. and Hodgson, E., 1983. Oxidation of thiobenzamide by the FAD containing and cytochrome P450 dependent monooxygenase of liver and lung microsomes. Biochem. Pharmacol., 32: 3419–3428.Google Scholar
- Ziegler, D.M., 1980. Microsomal flavin containing monooxygenase, oxygenation of nucleophilic nitrogen and sulfur compounds. In: Enzymatic Basis of Detoxification. Academic Press Inc., 201 pp.Google Scholar