Enhanced acetaminophen toxicity by activation of the pregnane X receptor

Toxicological Sciences

Volumn 82, Issue 2, 2004, Pages 374-380

  Guo, Gracel L ^a   Moffit, Jeff S ^b   Nicol, Christopher J ^a   Ward, Jerrold M ^c   Aleksunes, Lauren A ^b   Slitt, Angela L ^d   Kliewer, Steven A ^e   Manautou, Jose E ^b   Gonzalez, Frank J ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b UNIVERSITY OF CONNECTICUT   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

^d UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^e UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Acetaminophen; Hepatotoxicity; Nuclear receptor; PXR

Indexed keywords

16ALPHA CYANOPREGNENOLONE; ALANINE AMINOTRANSFERASE; CYTOCHROME P450 3A; GLUTATHIONE; N ACETYL 1,4 BENZOQUINONE IMINE; PARACETAMOL; PREGNANE X RECEPTOR;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL TISSUE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DISEASE SEVERITY; ENZYME INDUCTION; GENE EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HISTOPATHOLOGY; LIVER TOXICITY; MOLECULAR MECHANICS; MOUSE; NONHUMAN; NORTHERN BLOTTING; STATISTICAL ANALYSIS; STATISTICAL SIGNIFICANCE; URINALYSIS;

ACETAMINOPHEN; ANALGESICS, NON-NARCOTIC; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; BLOTTING, NORTHERN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 CYP3A; MEMBRANE PROTEINS; MICE; MICE, KNOCKOUT; OXIDOREDUCTASES, N-DEMETHYLATING; PREGNENOLONE CARBONITRILE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID; SULFHYDRYL COMPOUNDS;

STAPHYLOCOCCUS PHAGE 3A;

EID: 10044229222     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/kfh286     Document Type: Article

References (33)

1. Boyne, A. F., and Ellman, G. L. (1972). A methodology for analysis of tissue sulfhydryl components. Anal. Biochem. 46, 639-653.
2. Chen, C., Hennig, G. E., and Manautou, J. E. (2003). Hepatobiliary excretion of acetaminophen glutathione conjugate and its derivatives in transport-deficient (TR-) hyperbilirubinemic rats. Drug Metab. Dispos. 31, 798-804.
3. Chen, C., Hennig, G. E., Whiteley, H. E., Corton, J. C., and Manautou, J. E. (2000). Peroxisome proliferator-activated receptor alpha-null mice lack resistance to acetaminophen hepatotoxicity following clofibrate exposure. Toxicol. Sci. 57, 338-344.
4. Dahlin, D. C., Miwa, G. T., Lu, A. Y., and Nelson, S. D. (1984). N-acetyl-p-benzoquinone imine: A cytochrome P-450-mediated oxidation product of acetaminophen. Proc. Natl. Acad. Sci. U.S.A. 81, 1327-1331.
5. DiPetrillo, K., Wood, S., Kostrubsky, V., Chatfield, K., Bement, J., Wrighton, S., Jeffery, E., Sinclair, P., and Sinclair, J. (2002). Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol. Toxicol. Appl. Pharmacol. 185, 91-97.
6. Ellman, G. L. (1959). Tissue sulfhydryl groups. Arch. Biochem. Biophys. 82, 70-77.
7. Gonzalez, F. J., and Kimura, S. (2003). Study of P450 function using gene knockout and transgenic mice. Arch. Biochem. Biophys. 409, 153-158.
8. Gregus, Z., Madhu, C., and Klaassen, C. D. (1988). Species variation in toxication and detoxication of acetaminophen in vivo: A comparative study of biliary and urinary excretion of acetaminophen metabolites. J. Pharmacol. Exp. Ther. 244, 91-99.
9. Guo, G. L., Lambert, G., Negishi, M., Ward, J. M., Brewer, H. B., Jr., Kliewer, S. A., Gonzalez, F. J., and Sinal, C. J. (2003). Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J. Biol. Chem. 278, 45062-45071.
10. Guo, G. L., Staudinger, J., Ogura, K., and Klaassen, C. D. (2002). Induction of rat organic anion transporting polypeptide 2 by pregnenolone-16alpha-carbonitrile is via interaction with pregnane X receptor. Mol. Pharmacol. 61, 832-839.
11. Henderson, C. J., Wolf, C. R., Kitteringham, N., Powell, H., Otto, D., and Park, B. K. (2000). Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione S-transferase Pi. Proc. Natl. Acad. Sci. U.S.A. 97, 12741-12745.
12. Howie, D., Adriaenssens, P. I., and Prescott, L. F. (1977). Paracetamol metabolism following overdosage: Application of high performance liquid chromatography. J. Pharm. Pharmacol. 29, 235-237.
13. Jollow, D. J., Thorgeirsson, S. S., Potter, W. Z., Hashimoto, M., and Mitchell, J. R. (1974). Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and non-toxic dose of acetaminophen. Pharmacology 12, 251-271.
14. Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., and Edwards, P. A. (2002). Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J. Biol. Chem. 277, 2908-2915.
15. Kliewer, S. A. (2003). The nuclear pregnane X receptor regulates xenobiotic detoxification. J. Nutr. 133, 2444S-2447S.
16. Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterstrom, R. H., Perlmann, T., and Lehmann, J. M. (1998). An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92, 73-82.
17. Lee, S. S. T., Buters, J. T., Pineau, T., Fernandez-Salguero, P., and Gonzalez, F. J. (1996). Role of CYP2E1 in the hepatotoxicity of acetaminophen. J. Biol. Chem. 271, 12063-12067.
18. Lehmann, J. M., McKee, D. D., Watson, M. A., Willson, T. M., Moore, J. T., and Kliewer, S. A. (1998). The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 102, 1016-1023.
19. Madhu, C., and Klaassen, C. D. (1991). Protective effect of pregnenolone-16 alpha-carbonitrile on acetaminophen-induced hepatotoxicity in hamsters. Toxicol. Appl. Pharmacol. 109, 305-313.
20. Madhu, C., Maziasz, T., and Klaassen, C. D. (1992). Effect of pregnenolone-16 alpha-carbonitrile and dexamethasone on acetaminophen-induced hepatotoxicity in mice. Toxicol. Appl. Pharmacol. 115, 191-198.
21. Manautou, J. E., Tveit, A., Hoivik, D. J., Khairallah, E. A., and Cohen, S. D. (1996). Protection by clofibrate against acetaminophen hepatotoxicity in male CD-1 mice is associated with an early increase in biliary concentration of acetaminophen-glutathione adducts. Toxicol. Appl. Pharmacol. 140, 30-38.
22. Manyike, P. T., Kharasch, E. D., Kalhorn, T. F., and Slattery, J. T. (2000). Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin. Pharmacol. Ther. 67, 275-282.
23. Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., and Brodie, B. B. (1973). Acetaminophen-induced hepatic necrosis.IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 187, 211-217.
24. Moore, J. T., and Kliewer, S. A. (2000). Use of the nuclear receptor PXR to predict drug interactions. Toxicology 153, 1-10.
25. Ostapowicz, G., Fontana, R. J., Schiodt, F. V., Larson, A., Davern. T. J., Han, S. H., McCashland, T. M., Shakil, A. O., Hay, J. E., Hynan, L., Crippin, J. S., Blei, A. T., Samuel, G., Reisch, J., and Lee, W. M. (2002). Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern. Med. 137, 947-954.
26. Shankar, K., Vaidya, V. S., Corton, J. C., Bucci, T. J., Liu, J., Waalkes, M. P., and Mehendale, H. M. (2003). Activation of PPAR-alpha in streptozotocin-induced diabetes is essential for resistance against acetaminophen toxicity. Faseb J. 17, 1748-1750.
27. Sinclair, J., Jeffery, E., Wrighton, S., Kostrubsky, V., Szakacs, J., Wood, S., and Sinclair, P. (1998). Alcohol-mediated increases in acetaminophen hepatotoxicity: role of CYP2E and CYP3A. Biochem. Pharmacol. 55, 1557-1565.
28. Teng, S., Jekerle, V., and Piquette-Miller, M. (2003). Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab. Dispos. 31, 1296-1299.
29. Thummel, K. E., Lee, C. A., Kunze, K. L., Nelson, S. D., and Slattery, J. T. (1993). Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4. Biochem. Pharmacol. 45, 1563-1569.
30. Tonge, R. P., Kelly, E. J., Bruschi, S. A., Kalhorn, T., Eaton, D. L., Nebert, D. W., and Nelson, S. D. (1998). Role of CYP1A2 in the hepatotoxicity of acetaminophen: investigations using Cyp1a2 null mice. Toxicol. Appl. Pharmacol. 153, 102-108.
31. van Bree, L., Groot, E. J., and De Vries, J. (1989). Reduction by acetylsalicylic acid of paracetamol-induced hepatic glutathione depletion in rats treated with 4,4′-dichlorobiphenyl, phenobarbitone and pregnenolone-16-alpha-carbonitrile. J. Pharm. Pharmacol. 41, 343-345.
32. Zaher, H., Buters, J. T., Ward, J. M., Bruno, M. K., Lucas, A. M., Stern, S. T., Cohen, S. D., and Gonzalez, F. J. (1998). Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice. Toxicol. Appl. Pharmacol. 152, 193-199.
33. Zhang, J., Huang, W., Chua, S. S., Wei, P., and Moore, D. D. (2002). Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 298, 422-424.