Role of reactive metabolites in drug-induced hepatotoxicity

Handbook of Experimental Pharmacology

Volumn 196, Issue , 2010, Pages 165-194

  Park, B K ^a   Srivastava, A ^b   Maggs, J L ^b   Antoine, D J ^b   Williams, D P ^b   Smith, D A ^b  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b NONE

Author keywords

Hepatotoxicity; Metabolic activation; Reactive metabolites

Indexed keywords

AMINOTRANSFERASE; AMODIAQUINE; BROMFENAC; BROMOBENZENE; CARBON TETRACHLORIDE; CLOZAPINE; DRUG METABOLITE; FUROSEMIDE; GLUTATHIONE; ISONIAZID; NEVIRAPINE; NIMESULIDE; PARACETAMOL; PYRAZINAMIDE; RIFAMPICIN; TAMOXIFEN; THIOL; TOLCAPONE; TROGLITAZONE; TROVAFLOXACIN; ZILEUTON; FREE RADICAL;

AGRANULOCYTOSIS; AMINOTRANSFERASE BLOOD LEVEL; CHEMICAL REACTION; CHOLESTATIC HEPATITIS; CHRONIC HEPATITIS; DRUG ELIMINATION; DRUG FATALITY; DRUG TRANSFORMATION; ENDOMETRIUM CARCINOMA; HEPATITIS; HUMAN; LIVER CARCINOGENESIS; LIVER FAILURE; LIVER INJURY; LIVER METABOLISM; LIVER NECROSIS; LIVER TOXICITY; MACROMOLECULE; NONHUMAN; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; RASH; REVIEW; SIDE EFFECT; SKIN TOXICITY; TOXIC EPIDERMAL NECROLYSIS; UTERUS SARCOMA; ANIMAL; BIOTRANSFORMATION; CELL TRANSFORMATION; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; DRUG THERAPY; LIVER; LIVER TUMOR; METABOLISM; RISK ASSESSMENT; SIGNAL TRANSDUCTION; TOXIC HEPATITIS;

ANIMALS; BIOTRANSFORMATION; CELL TRANSFORMATION, NEOPLASTIC; DRUG THERAPY; DRUG-INDUCED LIVER INJURY; FREE RADICALS; HUMANS; LIVER; LIVER NEOPLASMS; RISK ASSESSMENT; SIGNAL TRANSDUCTION;

EID: 77949317937     PISSN: 01712004     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-642-00663-0_7     Document Type: Review

References (106)

1. Albano E, Rundgren M, Harvison PJ et al (1985) Mechanisms of N-acetyl-p-benzoquinone imine cytotoxicity. Mol Pharmacol 28:306-311
2. Almond LM, Boffito M, Hoggard PG et al (2004) The relationship between nevirapine plasma concentrations and abnormal liver function tests. AIDS Res Hum Retroviruses 20:716-722
3. Andringa KK, Bajt ML, Jaeschke H et al (2008) Mitochondrial protein thiol modifications in acetaminophen hepatotoxicity: effect on HMG-CoA synthase. Toxicol Lett 177:188-197
4. Argoti D, Liang L, Conteh A et al (2005) Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chem Res Toxicol 18:1537-1544
5. Baer BR, Wienkers LC, Rock DA (2007) Time-dependent inactivation of P450 3A4 by raloxifene: identification of Cys239 as the site of apoprotein alkylation. Chem Res Toxicol 20:954-964
6. Ball P, Mandell L, Niki Y et al (1999) Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Saf 21:407-421
7. Bambal RB, Hanzlik RP (1995) Bromobenzene 3, 4-oxide alkylates histidine and lysine side chains of rat liver proteins in vivo. Chem Res Toxicol 8:729-735
8. Benson JR, Pitsinis V (2003) Update on clinical role of tamoxifen. Curr Opin Obstet Gynecol 15:13-23
9. Boehringer-Ingelheim International (2005) Viramune product monograph. Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA
10. Boelsterli UA (2002) Nimesulide and hepatic adverse effects: roles of reactive metabolites and host factors. Int J Clin Pract 56(Suppl 128):30-36
11. Boelsterli UA, Ho HK, Zhou S, and Leow KY (2006) Bioactivation and hepatotoxicity of nitroaromatic drugs. Curr Drug Metab 7:715-727
12. Boocock DJ, Maggs JL, White IN et al (1999) a-Hydroxytamoxifen, a genotoxic metabolite of tamoxifen in the rat: identification and quantification in vivo and in vitro. Carcinogenesis 20:153-160
13. Boocock DJ, Maggs JL, Brown K et al (2000) Major inter-species differences in the rates of O-sulphonation and O-glucuronylation of a-hydroxytamoxifen in vitro: a metabolic disparity protecting human liver from the formation of tamoxifen-DNA adducts. Carcinogenesis 21:1851-1858
14. Brodie BB, Reid WD, Cho AK et al (1971) Possible mechanism of liver necrosis caused by aromatic organic compounds. Proc Natl Acad Sci USA 68:160-164
15. Buyse S, Vibert E, Sebagh M et al (2006) Liver transplantation for fulminant hepatitis related to nevirapine therapy. Liver Transplant 12:1880-1882
16. Caldwell GW, Yan Z (2006) Screening for reactive intermediates and toxicity assessment in drug discovery. Curr Opin Drug Discov Devel 9:47-60
17. Campian EC, Cai J, Benz FW (2002) Acrylonitrile irreversibly inactivates glyceraldehyde-3-phosphate dehydrogenase by alkylating the catalytically active cysteine 149. Chem Biol Interact 140:279-291
18. Carter SJ, Li XF, Mackey JR et al (2001) Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry. Electrophoresis 22:2730-2736
19. Casini AF, Pompella A, Comporti M (1984) Glutathione depletion, lipid peroxidation, and liver necrosis following bromobenzene and iodobenzene intoxication. Toxicol Pathol 12: 295-299 (Pubitemid 15175930)
20. Casini AF, Pompella A, Comporti M (1985) Liver glutathione depletion induced by bromobenzene, iodobenzene, and diethylmaleate poisoning and its relation to lipid peroxidation and necrosis. Am J Pathol 118:225-237
21. Centers for Disease Control and Prevention (2001) Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures-worldwide, 1997-2000. MMWR Morb Mortal Wkly Rep 49:1153-1156
22. Chen J, Mannargudi BM, Xu L, Uetrecht J (2008) Demonstration of the metabolic pathway responsible for nevirapine-induced skin rash. Chem Res Toxicol 21:1862-1870
23. Claes P, Wintzen M, Allard S et al (2004) Nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and Nacetylcysteine. Eur J Intern Med 15:255-258
24. Clarke JB, Maggs JL, Kitteringham NR et al (1990) Immunogenicity of amodiaquine in the rat. Int Arch Allergy Appl Immunol 91:335-342
25. Clarke S, Harrington P, Condon C et al (2000) Late onset hepatitis and prolonged deterioration in hepatic function associated with nevirapine therapy. Int J STD AIDS 11:336-337
26. Clawson GA (1989) Mechanisms of carbon tetrachloride hepatotoxicity. Pathol Immunopathol Res 8:104-112
27. Clemons M, Danson S, Howell A (2002) Tamoxifen ("Nolvadex"): a review. Cancer Treat Rev 28:165-180
28. Coles B, Wilson I, Wardman P et al (1988) The spontaneous and enzymatic reaction of N-acetyl-pbenzoquinonimine with glutathione: a stopped-flow kinetic study. Arch Biochem Biophys 264:253-260
29. Dahl JE, Becher R, Aarstad K et al (1990) Species differences in short term toxicity from inhalation exposure to bromobenzene. Arch Toxicol 64:370-376
30. Dai D, Tang J, Rose R et al (2001) Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 299:825-831
31. Damsten MC, Commandeur JN, Fidder A et al (2007) Liquid chromatography/tandem mass spectrometry detection of covalent binding of acetaminophen to human serum albumin. Drug Metab Dispos 35:1408-1417
32. Dart RC, Bailey E (2007) Does therapeutic use of acetaminophen cause acute liver failure? Pharmacotherapy 27:1219-1230
33. Davis DC, Potter WZ, Jollow DJ et al (1974) Species differences in hepatic glutathione depletion, covalent binding and hepatic necrosis after acetaminophen. Life Sci 14:2099-2109
34. Davis W, Venitt S, Phillips DH (1998) The metabolic activation of tamoxifen and a-hydroxytamoxifen to DNA-binding species in rat hepatocytes proceeds via sulphation. Carcinogenesis 19:861-866 (Pubitemid 28376779)
35. de Maat MM, Mathot RA, Veldkamp AI et al (2002) Hepatotoxicity following nevirapinecontaining regimens in HIV-1-infected individuals. Pharmacol Res 46:295-300
36. de Maat MM, ter Heine R, van Gorp EC et al (2003) Case series of acute hepatitis in a non-selected group of HIV-infected patients on nevirapine-containing antiretroviral treatment. AIDS 17:2209-2214
37. de Maat MM, Beijnen JH, Schellens JH et al (2005) Chronic hepatotoxicity after long-term antiretroviral treatment including nevirapine. J Infect 50:262-264
38. De Requena DG, Jimenez-Nacher I, Soriano V (2005) Changes in nevirapine plasma concentrations over time and its relationship with liver enzyme elevations. AIDS Res Hum Retroviruses 21:555-559
39. De Rosa SC, Zaretsky MD, Dubs JG et al (2000) N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 30:915-929
40. De Vos F, Van de Wiele C, Vandecapelle M et al (2001) High performance liquid chromatographic determination of 123-I labeled tamoxifen metabolites in human plasma. Nucl Med Biol 28:335-338
41. Dehal SS, Kupfer D (1999) Cytochrome P-450 3A and 2D6 catalyze ortho hydroxylation of 4-hydroxytamoxifen and 3-hydroxytamoxifen (droloxifene) yielding tamoxifen catechol: involvement of catechols in covalent binding to hepatic proteins. Drug Metab Dispos 27:681-688
42. den Besten C, Brouwer A, Rietjens IM et al (1994) Biotransformation and toxicity of halogenated benzenes. Hum Exp Toxicol 13:866-875
43. Derby LE, Gutthann SP, Jick H et al (1993) Liver disorders in patients receiving chlorpromazine or isoniazid. Pharmacotherapy 13:353-358
44. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents (2008) Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Office of AIDS Research Advisory Council (OARAC), pp 1-134
45. Druckova A, Mernaugh RL, Ham AJ et al (2007) Identification of the protein targets of the reactive metabolite of teucrin A in vivo in the rat. Chem Res Toxicol 20:1393-1408
46. Drummond NS, Vilar FJ, Naisbitt DJ et al (2006) Drug-specific T cells in an HIV-positive patient with nevirapine-induced hepatitis. Antivir Ther 11:393-395
47. Durand F, Bernuau J, Pessayre D et al (1995) Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid. Hepatology 21:929-932
48. Erickson DA, Mather G, Trager WF et al (1999) Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos 27:1488-1495
49. Evans DC, Watt AP, Nicoll-Griffith DA et al (2004) Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem Res Toxicol 17:3-16
50. Fan PW, Bolton JL (2001) Bioactivation of tamoxifen to metabolite E quinone methide: reaction with glutathione and DNA. Drug Metab Dispos 29:891-896
51. Fischer V, Haar JA, Greiner L et al (1991) Possible role of free radical formation in clozapine (clozaril)-induced agranulocytosis. Mol Pharmacol 40:846-853
52. Fisher R, Brendel K, Hanzlik RP (1993) Correlation of metabolism, covalent binding and toxicity for a series of bromobenzene derivatives using rat liver slices in vitro. Chem Biol Interact 88:191-198
53. Fisher B, Costantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90:1371-1388
54. Furr BJ, Jordan VC (1984) The pharmacology and clinical uses of tamoxifen. Pharmacol Ther 25:127-205
55. Gillette JR, Mitchell JR, Brodie BB (1974) Biochemical mechanisms of drug toxicity. Annu Rev Pharmacol 14:271-288
56. Goldkind L, Laine L (2006) A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiol Drug Saf 15:213-220
57. Goldring CE, Kitteringham NR, Elsby R et al (2004) Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice. Hepatology 39:1267-1276
58. Gonzalez FJ, Kimura S (1999) Role of gene knockout mice in understanding the mechanisms of chemical toxicity and carcinogenesis. Cancer Lett 143:199-204
59. Graham DJ, Drinkard CR, and Shatin D (2003) Incidence of idiopathic acute liver failure and hospitalized liver injury in patients treated with troglitazone. Am J Gastroenterol 98:175-179
60. Graham EE, Walsh RJ, Hirst CM et al (2008) Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore. J Pharmacol Exp Ther 326:657-671
61. Grewal KK, Rafeiro E, Racz WJ (1996) Bromobenzene and furosemide hepatotoxicity: alterations in glutathione, protein thiols, and calcium. Can J Physiol Pharmacol 74:257-264
62. Guengerich FP, Johnson WW, Ueng YF et al (1996) Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer. Environ Health Perspect 104(Suppl 3):557-562
63. Haas DW, Bartlett JA, Andersen JW et al (2006) Pharmacogenetics of nevirapine-associated hepatotoxicity: an adult AIDS Clinical Trials Group collaboration. Clin Infect Dis 43:783-786
64. Hanzlik RP, Koen YM, Theertham B et al (2007) The reactive metabolite target protein database (TPDB) - a web-accessible resource. BMC Bioinformat 8:95
65. Harrison AC, Kitteringham NR, Clarke JB et al (1992) The mechanism of bioactivation and antigen formation of amodiaquine in the rat. Biochem Pharmacol 43:1421-1430
66. Hatton CSR, Bunch C, Peto TEA et al (1986) Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria. Lancet 327:411-414
67. Henderson CJ, Smith AG, Ure J et al (1998) Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases. Proc Natl Acad Sci USA 95:5275-5280
68. He K, Talaat RE, Pool WF et al (2004) Metabolic activation of troglitazone: identification of a reactive metabolite and mechanisms involved. Drug Metab Dispos 32:639-646
69. Ikehata K, Duzhak TG, Galeva NA et al (2008) Protein targets of reactive metabolites of thiobenzamide in rat liver in vivo. Chem Res Toxicol 21:1432-1442
70. Ishak KG, Zimmerman HJ (1995) Morphologic spectrum of drug-induced hepatic disease. Gastroenterol Clin North Am 24:759-786
71. Jewell H, Maggs JL, Harrison AC et al (1995) Role of hepatic metabolism in the bioactivation and detoxication of amodiaquine. Xenobiotica 25:199-217
72. Jollow DJ, Mitchell JR, Zampaglione N et al (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151-169
73. Joshi EM, Heasley BH, Chordia MD et al (2004) In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity. Chem Res Toxicol 17:137-143
74. Kalgutkar AS, Soglia JR (2005) Minimising the potential for metabolic activation in drug discovery. Expert Opin Drug Metab Toxicol 1:91-142
75. Kao J, Carver MP (1990) Cutaneous metabolism of xenobiotics. Drug Metab Rev 22:363-410
76. Kaplowitz N (2001) Drug-induced liver disorders: implications for drug development and regulation. Drug Saf 24:483-490
77. Kawamoto Y, Nakamura Y, Naito Y et al (2000) Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-D12, 14-prostaglandin J2-induced expression of glutathione S-transferases. J Biol Chem 275:11291-11299
78. Kent UM, Lin HL, Mills DE et al (2006) Identification of 17-a-ethynylestradiol-modified active site peptides and glutathione conjugates formed during metabolism and inactivation of P450s 2B1 and 2B6. Chem Res Toxicol 19:279-287
79. Kitteringham NR, Powell H, Clement YN et al (2000) Hepatocellular response to chemical stress in CD-1 mice: induction of early genes and g-glutamylcysteine synthetase. Hepatology 32:321-333
80. Koen YM, Yue W, Galeva NA et al (2006) Site-specific arylation of rat glutathione S-transferase A1 and A2 by bromobenzene metabolites in vivo. Chem Res Toxicol 19:1426-1434
81. Koen YM, Gogichaeva NV, Alterman MA et al (2007) A proteomic analysis of bromobenzene reactive metabolite targets in rat liver cytosol in vivo. Chem Res Toxicol 20:511-519
82. Koenigs LL, Peter RM, Hunter AP et al (1999) Electrospray ionization mass spectrometric analysis of intact cytochrome P450: identification of tienilic acid adducts to P450 2C9. Biochemistry 38:2312-2319
83. Lammert C, Einarsson S, Saha C et al (2008) Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals. Hepatology 47:2003-2009
84. Larrey D, Castot A, Pessayre D et al (1986) Amodiaquine-induced hepatitis. A report of seven cases. Ann Intern Med 104:801-803
85. Lauterburg BH, Smith CV, Todd EL et al (1985a) Oxidation of hydrazine metabolites formed from isoniazid. Clin Pharmacol Ther 38:566-571
86. Lauterburg BH, Smith CV, Todd EL et al (1985b) Pharmacokinetics of the toxic hydrazino metabolites formed from isoniazid in humans. J Pharmacol Exp Ther 235:566-570
87. Lavie O, Barnett-Griness O, Narod SA et al (2008) The risk of developing uterine sarcoma after tamoxifen use. Int J Gynecol Cancer 18:352-356
88. Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279:1200-1205
89. Lee WM (2003) Acute liver failure in the United States. Semin Liver Dis 23:217-226
90. Leiro V, Fernandez-Villar A, Valverde D et al (2008) Influence of glutathione S-transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population. Liver Int 28:835-839
91. Li XF, Carter S, Dovichi NJ et al (2001) Analysis of tamoxifen and its metabolites in synthetic gastric fluid digests and urine samples using high-performance liquid chromatography with electrospray mass spectrometry. J Chromatogr A 914:5-12
92. Liebler DC (2008) Protein damage by reactive electrophiles: targets and consequences. Chem Res Toxicol 21:117-128
93. Liebler DC, Guengerich FP (2005) Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov 4:410-420
94. Ma L, Wen B, Ruan Q et al (2008) Rapid screening of glutathione-trapped reactive metabolites by linear ion trap mass spectrometry with isotope pattern-dependent scanning and postacquisition data mining. Chem Res Toxicol 21:1477-1483
95. MacCallum J, Cummings J, Dixon JM et al (2000) Concentrations of tamoxifen and its major metabolites in hormone responsive and resistant breast tumours. Br J Cancer 82:1629-1635
96. Macfarlane B, Davies S, Mannan K et al (1997) Fatal acute fulminant liver failure due to clozapine: a case report and review of clozapine-induced hepatotoxicity. Gastroenterology 112:1707-1709
97. Maellaro E, Del BB, Casini AF et al (1990) Early mitochondrial disfunction in bromobenzene treated mice: a possible factor of liver injury. Biochem Pharmacol 40:1491-1497
98. Maggs JL, Tingle MD, Kitteringham NR et al (1988) Drug-protein conjugates-XIV : Mechanisms of formation of protein-arylating intermediates from amodiaquine, a myelotoxin and hepatotoxin in man. Biochem Pharmacol 37:303-311
99. Maniar JK, Shah SR, Verma R et al (2006) Nevirapine-induced fulminant hepatitis. J Assoc Physicians India 54:957-958
100. Martin EA, Rich KJ, White IN et al (1995) 32P-postlabelled DNA adducts in liver obtained from women treated with tamoxifen. Carcinogenesis 16:1651-1654
101. Martin-Carbonero L, Nunez M, Gonzalez-Lahoz J et al (2003) Incidence of liver injury after beginning antiretroviral therapy with efavirenz or nevirapine. HIV Clin Trials 4:115-120
102. Martinez E, Blanco JL, Arnaiz JA et al (2001) Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy. AIDS 15:1261-1268
103. Mason RP, Fischer V (1992) Possible role of free radical formation in drug-induced agranulocytosis. Drug Saf 7(Suppl 1):45-50
104. Masubuchi N, Makino C, Murayama N (2007) Prediction of in vivo potential for metabolic activation of drugs into chemically reactive intermediate: correlation of in vitro and in vivo generation of reactive intermediates and in vitro glutathione conjugate formation in rats and human. Chem Res Toxicol 20:455-464
105. Mennes WC, van Holsteijn CW, van Iersel AA et al (1994) Interindividual variation in biotransformation and cytotoxicity of bromobenzene as determined in primary hepatocyte cultures derived from monkey and human liver. Hum Exp Toxicol 13:415-421
106. Miller EC, Miller JA (1947) The presence and significance of bound aminoazo dyes in the livers of rats fed p-dimethylaminobenzene. Cancer Res 7:468-480