Glucuronidation, a new metabolic pathway for pyrrolizidine alkaloids

Chemical Research in Toxicology

Volumn 23, Issue 3, 2010, Pages 591-599

  He, Yu Qi ^a   Yang, Li ^a   Liu, Hui Xin ^b   Zhang, Jiang Wei ^b   Liu, Yong ^b   Fong, Alan ^c   Xiong, Ai Zhen ^a   Lu, Yan Liu ^a   Yang, Ling ^b   Wang, Chang Hong ^a   Wang, Zheng Tao ^a  

^a SHANGHAI UNIVERSITY OF TRADITIONAL CHINESE MEDICINE   (China)

^b DALIAN INSTITUTE OF CHEMICAL PHYSICS   (China)

^c SARAWAK GENERAL HOSPITAL   (Malaysia)

Author keywords

[No Author keywords available]

Indexed keywords

ADONIFOLINE; GLUCURONIC ACID; GLUCURONOSYLTRANSFERASE; ISOLINE; MONOCROTALINE; PYRROLIZIDINE ALKALOID; SENECIONINE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE;

ANIMAL EXPERIMENT; ARTICLE; BINDING SITE; CATALYSIS; CATTLE; CHEMICAL STRUCTURE; CONTROLLED STUDY; DOG; GLUCURONIDATION; GUINEA PIG; HUMAN; IN VITRO STUDY; KINETICS; LIVER MICROSOME; LIVER TOXICITY; MICHAELIS MENTEN KINETICS; MOUSE; NONHUMAN; RABBIT; RAT; SHEEP; SWINE;

ANIMALS; CATTLE; CRICETINAE; DOGS; HUMANS; MICE; MICROSOMES, LIVER; PYRROLIZIDINE ALKALOIDS; RABBITS; RATS; URIDINE DIPHOSPHATE GLUCURONIC ACID;

ANIMALIA; BOS; CANIS FAMILIARIS; CAVIA; MUS; ORYCTOLAGUS CUNICULUS; OVIS ARIES; RATTUS; SUIDAE;

EID: 77949362123     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx900328f     Document Type: Article

References (33)

1. Roeder, E. (1995) Medicinal plants in Europe containing pyrrolizidine alkaloids. Pharmazie 50, 83-98.
2. Hartmann, T., Witte, L., Ehmke, A., Theuring, C., Rowell-Rahier, M., and Pasteels, J. M. (1997) Selective sequestration and metabolism of plant derived pyrrolizidine alkaloids by chrysomelid leaf beetles. Phytochemistry 45, 489-497.
3. Fu, P. P., Xia, Q., Lin, G., and Chou, M. W. (2004) Pyrrolizidine alkaloidssGenotoxicity, metabolism enzymes, metabolic activation, and mechanisms. Drug Metab. ReV. 36, 1-55.
4. Stegelmeier, B. L., Edgar, J. A., Colegate, S. M., Gardner, D. R., Schoch, T. K., Coulombe, R. A., and Molyneux, R. J. (1999) Pyrrolizidine alkaloid plants, metabolism and toxicity. J. Nat. Toxins 8, 95-116.
5. Yan, C. C., and Huxtable, R. J. (1995) Relationship between glutathione concentration and metabolism of the pyrrolizidine alkaloid, monocrotaline, in the isolated, perfused liver. Toxicol. Appl. Pharmacol. 130, 132-139.
6. Xia, Q., Yan, J., Chou, M. W., and Fu, P. P. (2008) Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, heliotrine. Toxicol. Lett. 178, 77-82.
7. Chung, W. G., and Buhler, D. R. (1995) Major factors for the susceptibility of guinea pig to the pyrrolizidine alkaloid jacobine. Drug Metab. Dispos. 23, 1263-1267.
8. Huan, J. Y., Miranda, C. L., Buhler, D. R., and Cheeke, P. R. (1998) Species differences in the hepatic microsomal enzyme metabolism of the pyrrolizidine alkaloids. Toxicol. Lett. 99, 127-137.
9. Lin, G., Tang, J., Liu, X. Q., Jiang, Y., and Zheng, J. (2007) Deacetylclivorine: A gender-selective metabolite of clivorine formed in female Sd rat liver microsomes. Drug Metab. Dispos. 35, 607-613.
10. King, C. D., Rios, G. R., Green, M. D., and Tephly, T. R. (2000) UDP-glucuronosyltransferases. Curr. Drug Metab. 1, 143-161.
11. Malfatti, M. A., and Felton, J. S. (2001) N-glucuronidation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-hydroxy-PhIP by specific human UDP-glucuronosyltransferases. Carcinogenesis 22, 1087-1093.
12. Mattocks, A. R., Jukes, R., and Brown, J. (1989) Simple procedures for preparing putative toxic metabolites of pyrrolizidine alkaloids. Toxicon 27, 561-567.
13. Chou, M. W., Wang, Y. P., Yan, J., Yang, Y. C., Beger, R. D., Williams, L. D., Doerge, D. R., and Fu, P. P. (2003) Riddelliine N-oxide is a phytochemical and mammalian metabolite with genotoxic activity that is comparable to the parent pyrrolizidine alkaloid riddelliine. Toxicol. Lett. 145, 239-247.
14. Xiong, A., Li, Y., Yang, L., Gao, J., He, Y., Wang, C., and Wang, Z. (2009) Simultaneous determination of senecionine, adonifoline and their metabolites in rat serum by UPLC-ESIMS and its application in pharmacokinetic studies. J. Pharm. Biomed. Anal. 50, 1070-1074.
15. Walsky, R. L., and Obach, R. S. (2004) Validated assays for human cytochrome p450 activities. Drug Metab. Dispos. 32, 647-660.
16. 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.
17. Liu, H.-X., Liu, Y., Zhang, J.-W., Li, W., Liu, H.-T., and Yang, L. (2008) UDP-glucuronosyltransferase 1A6 is the major isozyme responsible for protocatechuic aldehyde glucuronidation in human liver microsomes. Drug Metab. Dispos. 36, 1562-1569.
18. Tang, J., Akao, T., Nakamura, N., Wang, Z. T., Takagawa, K., Sasahara, M., and Hattori, M. (2007) In vitro metabolism of isoline, a pyrrolizidine alkaloid from Ligularia duciformis, by rodent liver microsomal esterase and enhanced hepatotoxicity by esterase inhibitors. Drug Metab. Dispos. 35, 1832-1839.
19. Luo, H., Hawes, E. M., McKay, G., and Midha, K. K. (1992) Synthesis and characterization of quaternary ammonium-linked glucuronide metabolites of drugs with an aliphatic tertiary amine group. J. Pharm. Sci. 81, 1079-1083.
20. Uchaipichat, V., Mackenzie, P. I., Elliot, D. J., and Miners, J. O. (2006) Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) "probes" for human udp-glucuronosyltransferases. Drug Metab. Dispos. 34, 449-456.
21. Liu, H.-X., He, Y.-Q., Hu, Y., Liu, Y., Zhang, J.-W., Li, W., Zheng, TaoWang., and Yang, L. (2008) Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultraperformance liquid chromatography with MS detection. J. Chromatogr. B 870, 84-90.
22. Kassahun, K., Mattiuz, E., Franklin, R., and Gillespie, T. (1998) Olanzapine 10-N-glucuronide. A tertiary N-glucuronide unique to humans. Drug Metab. Dispos. 26, 848-855.
23. El-Shazly, A. (2002) Pyrrolizidine alkaloid profiles of some Senecio species from Egypt. Z. Naturforsch. C 57, 429-433.
24. Chiu, S. H., and Huskey, S. W. (1998) Species differences in N-glucuronidation. Drug Metab. Dispos. 26, 838-847.
25. Li, S.-L., Lin, G., Fu, P. P., Chan, C.-L., Li, M., Jiang, Z.-H., and Zhao, Z.-Z. (2008) Identification of five hepatotoxic pyrrolizidine alkaloids in a commonly used traditional Chinese medicinal herb, Herba Senecionis scandentis (Qianliguang). Rapid Commun. Mass Spectrom. 22, 591-602.
26. Zhang, F., Wang, C. H., Wang, W., Chen, L. X., Ma, H. Y., Zhang, C. F., Zhang, M., Bligh, S. W., and Wang, Z. T. (2007) Quantitative analysis by HPLC-MS2 of the pyrrolizidine alkaloid adonifoline in Senecio scandens. Phytochem. Anal. 19, 25-31.
27. Vincic, L., Orr, F. W., Warner, D. J., Suyama, K. L., and Kay, J. M. (1989) Enhanced cancer metastasis after monocrotaline-induced lung injury. Toxicol. Appl. Pharmacol. 100, 259-270.
28. Green, M. D., and Tephly, T. R. (1996) Glucuronidation of amines and hydroxylated xenobiotics and endobiotics catalyzed by expressed human UGT1.4 protein. Drug Metab. Dispos. 24, 356-363.
29. Spencer, J. P., Chowrimootoo, G., Choudhury, R., Debnam, E. S., Srai, S. K., and Rice-Evans, C. (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett. 458, 224-230.
30. Zhang, W., Liu, W., Innocenti, F., and Ratain, M. J. (2007) Searching for tissue-specific expression pattern-linked nucleotides of UGT1A isoforms. PLoS One 2, e396.
31. Buckley, D. B., and Klaassen, C. D. (2007) Tissue-and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice. Drug Metab. Dispos. 35, 121-127.
32. Shelby, M. K., Cherrington, N. J., Vansell, N. R., and Klaassen, C. D. (2003) Tissue mRNA expression of the rat UDP-glucuronosyltransferase gene family. Drug Metab. Dispos. 31, 326-333.
33. Vargas, M., and Franklin, M. R. (1997) Intestinal UDP- glucuronosyltransferase activities in rat and rabbit. Xenobiotica 27, 413-421.