N-Deacetyl ketoconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes

Toxicology

Volumn 117, Issue 2-3, 1997, Pages 123-131

  Rodriguez, Rosita J ^a   Acosta Jr , Daniel ^a  

^a UNIVERSITY OF CINCINNATI   (United States)

Author keywords

Azole derivatives; Flavin containing monooxygenases; Hepatocytes; Hepatotoxicity; Ketoconazole; Metabolite; Methimazole; N Deacetyl ketoconazole; n Octylamine; Primary cultures

Indexed keywords

DRUG METABOLITE; KETOCONAZOLE; THIAMAZOLE; UNSPECIFIC MONOOXYGENASE;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; LIVER CELL CULTURE; LIVER TOXICITY; NONHUMAN; PRIORITY JOURNAL; RAT;

ANIMALS; ANTIFUNGAL AGENTS; CELL MEMBRANE; CELLS, CULTURED; COLORING AGENTS; FEMALE; KETOCONAZOLE; L-LACTATE DEHYDROGENASE; LIVER; MALE; MITOCHONDRIA; OXIDATION-REDUCTION; OXYGENASES; RATS; RATS, SPRAGUE-DAWLEY; TETRAZOLIUM SALTS; THIAZOLES;

ANIMALIA;

EID: 0031588765     PISSN: 0300483X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0300-483X(96)03560-3     Document Type: Article

References (42)

1. Acosta, D., Anuforo, D. and Smith, R.V. (1980) Preparation of primary monolayer cultures of postnatal rat liver cells. J. Tissue Cult. Methods 6, 35-37.
2. Acosta, D., Sorensen, E.M.B., Anuforo, D.C., Mitchell, D.B., Ramos, K., Santone, K.S. and Smith, M.A. (1985) An in vitro approach to the study of target organ toxicity of drugs and chemicals. In Vitro Cell. Dev. Biol. 21, 495-504.
3. Benson, G.D., Anderson, P.K., Combes, B. and Ishak, K.G. (1988) Prolonged jaundice following ketoconazole-induced hepatic injury. Dig. Dis. Sci. 33, 240-246.
4. Bercoff, E., Bernuau, J., Degott, C, Kalis, B., Lemaire, A., Tilly, H., Rueff, B. and Benhamou, J.P. (1985) Ketoconazole-induced fulminate hepatitis. Gut 26, 636-638.
5. Bodey, G.P. (1992) Azole antifungal agents. Clin. Infect. Dis. 14 (supp1.), S161-S169.
6. Brass, C., Galgiani, J.N., Blaschke, T.F., Defelice, R., O'Reilly, R.A. and Stevens, D.A. (1982) Disposition of ketoconazole, an oral antifungal, in humans. Antimicrob. Agents Chemother. 21, 151-158.
7. Brusko, C.S. and Marten, J.T. (1991) Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis. DICP, Ann. Pharmacother. 25, 1321-1325.
8. Cashman, J.R. and Ziegler, D.M. (1986) Contribution of N-oxygenation to the metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by various liver preparations. Mol. Pharmacol. 39, 163-167.
9. Cauwenbergh, G. (1989) Safety aspects of ketoconazole, the most commonly used systemic antifungal. Mycoses 32 (Suppl. 2), 59-63.
10. Daneshmend, T.K. and Warnock, D.W. (1988) Clinical pharmacokinetics of ketoconazole. Clin. Pharmacokinet. 14, 13-34.
11. Dannan, G.A., Guengerich, F.P. and Waxman, D.J. (1986) Hormonal regulation of rat liver microsomal enzymes. J. Biol. Chem. 261, 10728-10735.
12. Di Monte, D.A., Wu, E.Y., Irwin, I., Delanney, L.E. and Langston, J.W. (1991) Biotransformation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in primary cultures of mouse astrocytes. J. Pharmacol. Exp. Ther. 258, 594-600.
13. Gascoigne, E.W., Barton. G.J., Michaels, M., Meuldermans, W. and Heykants, J. (1981) The kinetics of ketoconazole in animals and man. Clin. Res. Rev. 1, 177-187.
14. Grant, S.M. and Clissold, S.P. (1990) Fluconazole, a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs 39, 877-916.
15. Hann, S.K., Kim, J.B., Han, K.H. and Park, Y.K. (1993) Itraconazole-induced acute hepatitis. Br. J. Dermatol. 129, 500-501.
16. Heel, R.C., Brogden, R.N., Carmine, A., Morley, P.A., Speight, T.M. and Avery, G.S. (1982) Ketoconazole, A review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs 23, 1-36.
17. Huang, Y-C., Colizzi, J.L., Bierman, R.H., Woestenborghs, R. and Heykants, J. (1986) Pharmacokinetics and dose proportionality of ketoconazole in normal volunteers. Antimicrob. Agents Chemother. 30, 206-210.
18. Knight, T.E., Shikuma, C.Y. and Knight, J. (1991) Ketoconazole-induced fulminant hepatitis necessitating liver transplantation. J. Am. Acad. Dermatol. 25, 398-400.
19. Lake-Bakaar, G., Scheuer, P.J. and Sherlock, S. (1987) Hepatic reactions associated with ketoconazole in the United Kingdom. Br. Med. J. 294, 419-422.
20. Lavrijsen, A.P.M., Balmus, K.J., Nugteren-Huying, W.M., Roldaan, A.C., van't Wout, J.W. and Stricker, B.H. (1992) Hepatic injury associated with itraconazole. Lancet 340, 251-252.
21. Lemoine, A., Williams, D.E., Cresteil, T. and Leroux, J.P (1991) Hormonal regulation of microsomal flavin-containing monooxygenase, tissue-dependent expression and substrate specificity. Mol. Pharmacol. 40, 211-217.
22. Loose, D.S., Kan, P.B., Hirst, M.A., Marcus, R.A. and Feldman, D. (1983) Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P-450 dependent enzymes. J. Clin. Invest. 71, 1495-1499.
23. Maurice, M., Pichard, L., Daujat, M., Fabre, I., Joyeux, H., Domergue, J. and Maurel, P. (1992) Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J. 6, 752-758.
24. Meredith, C.G., Maldonado, A. and Speeg, K.V. (1985) The effect of ketoconazole on hepatic oxidative drug metabolism in the rat in vivo and in vitro. Drug Metab. Dispos. 13, 156-162.
25. Mitchell, D.B., Santone, K.S. and Acosta, D. (1980) Evaluation of cytotoxicity in cultured cells by enzyme leakage. J. Tissue Cult. Methods 6, 113-116.
26. Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival, Application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63.
27. Rodrigues, A.D., Gibson, G.G., Ioannides, C. and Parke, D.V. (1987) Interactions of imidazole antifungal agents with purified cytochrome P-450 proteins. Biochem. Pharmacol. 36, 4277-4281.
28. Rodriguez, R.J., Ziegler, D.M. and Acosta, D. (1995) Metabolism of ketoconazole and N-deacetyl ketoconazole by hepatic microsomes and flavin-containing monooxygenases. Pharm. Res. 12, S383.
29. Rodriguez, R.J. and Acosta, D. (1995) Comparison of ketoconazole-and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology 96, 83-92.
30. Rodriguez, R.J., Davila, J.C. and Acosta, D. (1996) Establishment of flavin-containing monooxygenases in hepatic microsomes obtained from primary cultures of rat hepatocytes. Toxicologist 30, 215.
31. Santen, R.J., Vanden Bossche, H., Symoens, J., Brugmans, J. and De Coster, R. (1983) Site of low dose ketoconazole on androgen biosynthesis in men. J. Clin. Endocrinol. Metab. 57, 732-736.
32. Sheets, J.J. and Mason, J.I. (1984) Ketoconazole, a potent inhibitor of cytochrome P-450 dependent drug metabolism in rat liver. Drug Metab. Dispos. 12, 603-606.
33. Skett, P., Mode, A., Rafter, J., Sahlin, L. and Gustafsson, J.-A. (1980) The effects of gonadectomy and hypophysectomy on the metabolism of imipramine and lidocaine by the liver of male and female rats. Biochem. Pharmacol. 29, 2759-2762.
34. Strandberg, T.E., Tilvis, R.S. and Miettinen, T.A. (1987) Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver. Lipids 22, 1020-1024.
35. Stricker, B.H., Blok, A.P.R., Bronkhorst, F.B., Van Parys, G.E. and Desmet, V.J. (1986) Ketoconazole-associated hepatic injury, a clinicopathological study of 55 cases. J. Hepatol. 3, 399-406.
36. Sugar, A.M., Alsip, S.G., Galgiani, J.N., Graybill, J.R., Dismukes, W.E., Cloud, G.A., Craven, P.C. and Stevens, D.A. (1987) Pharmacology and toxicity of high-dose ketoconazole. Antimicrob. Agents Chemother. 31, 1874-1878.
37. Svejgaard, E. and Ranek (1982) Hepatic dysfunction and ketoconazole therapy. Ann. Intern. Med. 96, 788-789.
38. Vanden Bossche, H., Marichal, P., Gorrens, J., Geerts, H. and Janssen, P.A. (1988) Basis for the search for new antifungal drugs. Ann. New York Acad. Sci. 544, 191-207.
39. Wells, C. and Lever, A.M.L. (1992) Dose dependent fluconazole hepatotoxicity proven on biopsy and rechallenge. J. Infect. 24, 111-112.
40. Whitehouse, L.W., Menzies, A., Dawson, B., Zamecnik, J. and Sy, W-W. (1990) Deacetylated ketoconazole, a major ketoconazole isolated from mouse liver. J. Pharm. Biomed. Anal. 8, 603-606.
41. Whitehouse, L.W., Menzies, A., Dawson, B., Cyr, T.D., By, A.W., Black, D.B. and Zamecnik, J. (1994a) Mouse hepatic metabolites of ketoconazole, isolation and structure elucidation. J. Pharm. Biomed. Anal. 12, 1425-1441.
42. Whitehouse, L.W., Menzies, A., Mueller, R. and Pontefract, R. (1994b) Ketoconazole-induced hepatic phospholipidosis in the mouse and its association with de-N-acetyl ketoconazole. Toxicology 94, 81-95.