Abstract
Drugs containing the imidazole ring have been reported to exert a potent inhibitory effect on microsomal mixed function mono-oxygenase (MFO) activity in man and experimental animals (Wilkinson et al. 1972; Pelkonen and Puurunen 1980; Murray 1984; Kapetanovic and Kupferberg 1984; Koop and Coon 1984; Kadderis and Rickert 1985; Horai et al. 1985). Such effects, mainly found in the liver and, recently, also in gonad and adrenal tissues (Mason et al. 1985), depend upon many factors. Species- and age-related differences have been established (Tu et al. 1981; Hajek and Novak 1982; Reinke et al. 1985). However, single or repeated administration of some imidazole derivatives was shown to result in an inhibition or an induction of MFO activity (Hajek and Novak 1982). By considering the multiplicity of cytochrome (Cyt) P450 isoenzymes in microsomes, these conflicting results become understandable.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Biagi GL, Barbaro AM, Guerra MC, Cantelli-Forti G, Aicardi G, Borea PA (1983) Quantitative relationship between structure and mutagenic activity in a series of 5-nitroimidazoles. Teratogen Carcin Mut 3:429–438
Cantelli-Forti G, Aicardi G, Guerra MC, Barbaro AM, Biagi GL (1983) Mutagenicity of a series of 25 nitroimidazoles and two nitrothiazoles in Salmonella typhimurium. Teratogen Care Mut 3:51–63
Cantelli-Forti G, Paolini M, Hrelia P, Corsi C, Biagi GL, Bronzetti G (1984) NADPH-generating system: influences on microsomal mono-oxygenase stability during incubations for the liver microsomal assay with rat and mouse S9 fractions. Mutat Res 129:291–297
Cantelli-Forti G, Hrelia P, Paolini M, Bronzetti G, Biagi GL (1985) The organo-specific activity of metronidazole and azanidazole in the intrasanguinous host-mediated assay. Drug Exp Clin Res 11:755–759
Gervasi PG, Benedetti D, Citti L, Del Monte M, Turchi G (1984) Dinemorphan N-demethylation by mouse liver microsomes. Experientia 40:180–182
Hajek KK, Novak RF (1982) Spectral and metabolic properties of liver microsomes from imidazole-pretreated rabbit. Biochem Biophys Res Commun 108:664–672
Horai Y, White PF, Trevor AY (1985) The effect of etomidate on rabbit liver microsomal drug metabolism in vitro. Drug Metab Dispos 13:364–367
Kapetanovic IM, Kupferberg HJ (1984) Nafimidone and imidazole anticonvulsant and its metabolite as potent inhibitors of microsomal metabolism of phenytoin and carbamazepine. Drug Metab Dispos 12:560–563
Kadderis GL, Rickert DE (1985) Loss of rat liver microsomal cytochrome P-450 during methimazole and metabolism. Drug Metab Dispos 13:58–61
Klotz AV, Stageman VV, Walsh C (1984) An alternative 7-ethoxycoumarin O-deethylase activity assay: a continuous visible spectrophotometric method for measurement of cytochrome P-450 mono-oxygenase activity. Anal Biochem 140:138–145
Koop DR, Coon MJ (1984) Purification of liver microsomal cytochrome P-450 isoenzymes 3a and 6 from imidazole treated rabbits. Mol Pharmacol 25:494–501
Mason JI, Murray BA, Olcott M, Sheets JJ (1985) Imidazole antimycotics: inhibitors of steroid aromatase. Biochem Pharmacol 34:1087–1092
Murray M (1984) In vitro effects of quinoline derivatives on cytochrome P-450 and aminopyrine N-demethylase activity in rat hepatic microsomes. Biochem Pharmacol 33:3277–3281
Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378
Pelkonen O, Puurunen J (1980) The effect of cimetidine on in vitro and in vivo microsomal drug metabolism in the rat. Biochem Pharmacol 29:3075–3080
Reinke LA, Sexter SH, Rikans LE (1985) Comparison of ethanol and imidazole pretreatments on hepatic mono-oxygenase activities in the rat. Res Commun Chem Pathol Pharmacol 47:97–105
Tu YY, Sonnenberg J, Lewis KF, Yang CS (1981) Pyrazole-induced cytochrome P-450 in rat liver microsomes: an isozyme with high affinity for dimethylnitrosamine. Biochem Biophys Res Commun 103:905–912
Warkman P (1980) Pharmacokinetics of hypoxic cell radiosensitizers. Cancer Clin Trials 3:237–241
Wilkinson CF, Hetnarski CF, Yellin TO (1972) Imidazole-derivatives. A new class of microsomal enzyme inhibitors. 21:3187–3192
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Springer-Verlag
About this paper
Cite this paper
Cantelli-Forti, G., Paolini, M., Hrelia, P., Sapigni, E., Biagi, G.L. (1987). Effects of Metronidazole, Azanidazole, and Azathioprine on Cytochrome P450 and Various Mono-Oxygenase Activities in Hepatic Microsomes from Control and Induced Mice. In: Chambers, C.M., Chambers, P.L., Davies, D.S. (eds) Mechanisms and Models in Toxicology. Archives of Toxicology, Supplement, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-72558-6_48
Download citation
DOI: https://doi.org/10.1007/978-3-642-72558-6_48
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-17614-5
Online ISBN: 978-3-642-72558-6
eBook Packages: Springer Book Archive