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The long persistence of pyrrolizidine alkaloid-derived pyrrole-protein adducts in vivo: Kinetic study following multiple exposures of a pyrrolizidine alkaloid containing extract of Gynura japonica

Chen, Yan, Xiong, Fen, Wang, Weiqian, Jiang, Kaiyuan, Ye, Xuanling, Deng, Gang, Wang, Changhong, Yang, Li, Xiong, Aizhen, Wang, Zhengtao·2020·Toxicology Letters
DOI 10.1016/j.toxlet.2020.01.021
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Abstract

Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T 1/2ke∼ 184.6 h, ∼7.7 days) than in serum (T 1/2ke ∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification.

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Research works printed but not linked: 38

  1. Cooper, 1996, A simple procedure for determining the aqueous half-lives of pyrrolic metabolites of pyrrolizidine alkaloids, Toxicon., 34, 604, 10.1016/0041-0101(95)00169-7 · DOI
  2. Cooper, 1999, The relationship between reactivity of metabolites of pyrrolizidine alkaloids and extrahepatic toxicity, Proc. West. Pharmacol. Soc., 42, 13
  3. Cooperative Group for Hepatic and Gall Diseases, 2017, Expert consensus on diagnosis and treatment of pyrrolidine alkaloids-related sinusoidal obstruction syndrome, J Clin Hepatol., 33, 1627
  4. Dai, 2007, Gynura root induces hepatic veno-occlusive disease: a case report and review of the literature, World J. Gastroenterol., 13, 1628, 10.3748/wjg.v13.i10.1628 · DOI
  5. DeLeve, 2002, Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease), Semin. Liver Dis., 22, 27, 10.1055/s-2002-23204 · DOI
  6. Dignan, 2013, BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation, Br. J. Haematol., 163, 444, 10.1111/bjh.12558 · DOI
  7. Fang, 2014, Mass-spectrometry-directed analysis and purification of pyrrolizidine alkaloid cis/trans isomers in Gynura japonica, J. Sep. Sci., 37, 2032, 10.1002/jssc.201400314 · DOI
  8. Fu, 2004, Pyrrolizidine alkaloids-genotoxicity, metabolism enzymes, metabolic activation, and mechanisms, Drug Metab. Rev., 36, 1, 10.1081/DMR-120028426 · DOI
  9. Gao, 2018, Evidence-based clinical study of pyrrolizidine alkaloids associated with hepatic sinusoidal obstruction syndrome, Chin J Gastroenterol Hepatol., 27, 979
  10. Gao, 2012, Definitive diagnosis of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids, J. Dig. Dis., 13, 33, 10.1111/j.1751-2980.2011.00552.x · DOI · Paper page
  11. Gao, 2015, Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome, Drug Des. Devel. Ther., 9, 4861, 10.2147/DDDT.S87858 · DOI · Paper page
  12. Guo, 2018, Clinical features of sinusoidal obstruction syndrome induced by pyrrolidine alkaloids in China, J Clin Hepatol., 34, 1277
  13. Helmy, 2006, Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome, Aliment. Pharmacol. Ther., 23, 11, 10.1111/j.1365-2036.2006.02742.x · DOI
  14. Hu, 2019, Research and prospect of sinusoidal obstruction syndrome caused by Gynura Segetum, J Syst Med., 4, 196
  15. Huxtable, 1994, Relationship between in vitro metabolism of pyrrolizidine alkaloids and extrahepatic toxicity in vivo, Proc. West. Pharmacol. Soc., 37, 109
  16. Huxtable, 1996, Physicochemical and metabolic basis for the differing neurotoxicity of the pyrrolizidine alkaloids, trichodesmine and monocrotaline, Neurochem. Res., 21, 141, 10.1007/BF02529131 · DOI
  17. Ji, 2008, The toxic effect of pyrrolizidine alkaloid clivorine on the human embryonic kidney 293 cells and its primary mechanism, Exp. Toxicol. Pathol., 60, 87, 10.1016/j.etp.2007.11.010 · DOI
  18. Li, 2018, Progress in the pathogenesis, clinical diagnosis and treatment of hepatic sinus obstruction syndrome caused by tusanqi, Chin Hepatol., 23, 540
  19. Li, 2011, Hepatotoxicity and tumorigenicity induced by metabolic activation of pyrrolizidine alkaloids in herbs, Curr. Drug Metab., 12, 823, 10.2174/138920011797470119 · DOI
  20. Lin, 2000, Characterization of two structural forms of otonecine-type pyrrolizidine alkaloids from Ligularia hodgsonii by NMR spectroscopy, J. Nat. Prod., 63, 857, 10.1021/np9906119 · DOI
  21. Lin, 2011, Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum, J. Hepatol., 54, 666, 10.1016/j.jhep.2010.07.031 · DOI · Paper page
  22. Lu, 2018, The role of formation of pyrrole-ATP synthase subunit beta adduct in pyrrolizidine alkaloid-induced hepatotoxicity, Arch. Toxicol., 92, 3403, 10.1007/s00204-018-2309-6 · DOI
  23. Ma, 2018, Pyrrole-protein adducts: a biomarker of pyrrolizidine alkaloid-induced hepatotoxicity, J. Food Drug Anal., 26, 965, 10.1016/j.jfda.2018.05.005 · DOI
  24. Ma, 2019, Pyrrole-hemoglobin adducts, a more feasible potential biomarker of pyrrolizidine alkaloid exposure, Chem. Res. Toxicol., 2, 1027, 10.1021/acs.chemrestox.8b00369 · DOI
  25. Moreira, 2018, Pyrrolizidine alkaloids: chemistry, pharmacology, toxicology and food safety, Int. J. Mol. Sci., 19, 2, 10.3390/ijms19061668 · DOI
  26. Neuman, 2015, Hepatotoxicity of pyrrolizidine alkaloids, J. Pharm. Pharm. Sci., 18, 825, 10.18433/J3BG7J · DOI
  27. Qi, 2019, Clinical analysis of 5 cases of hepatic sinus obstruction syndrome caused by tusanqi, Chin J Integr Trad West Med Dig., 27, 548
  28. Ruan, 2014, Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis, Chem. Res. Toxicol., 27, 1030, 10.1021/tx500071q · DOI
  29. Ruan, 2015, Blood pyrrole-protein adducts-A biomarker of pyrrolizidine alkaloid-induced liver injury in humans, J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev., 33, 404
  30. Tang, 2011, Pyrrolizidine alkaloids-containing Chinese medicines in the Chinese pharmacopoeia and related safety concerns, Acta Pharm. Sin. B, 46, 762
  31. Wang, 2005, Metabolic activation of the tumorigenic pyrrolizidine alkaloid, monocrotaline, leading to DNA adduct formation in vivo, Int. J. Environ. Res. Public Health, 2, 74, 10.3390/ijerph2005010074 · DOI
  32. Wang, 2014, Metabolic activation of pyrrolizidine alkaloids leading to phototoxicity and photogenotoxicity in human HaCaT keratinocytes, J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev., 32, 362
  33. Wang, 2015, Tusanqi-related sinusoidal obstruction syndrome in China: a systematic review of the literatures, Medicine., 94, e942, 10.1097/MD.0000000000000942 · DOI
  34. Wiedenfeld, 2011, Plants containing pyrrolizidine alkaloids: toxicity and problems, Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess., 28, 282, 10.1080/19440049.2010.541288 · DOI
  35. Willmot, 1920, Senecio disease or cirrhosis of the liver due to Senecio poisoning, Lancet, 2, 848, 10.1016/S0140-6736(01)00020-4 · DOI
  36. Xiong, 2016, Clivorine, an otonecine pyrrolizidine alkaloid from Ligularia species, impairs neuronal differentiation via NGF-induced signaling pathway in cultured PC12 cells, Phytomedicine, 23, 931, 10.1016/j.phymed.2016.06.006 · DOI
  37. Xiong, 2019, Comparative analysis of toxic components in different medicinal parts of Gynura japonica and its toxicity assessment on mice, Phytomedicine, 54, 77, 10.1016/j.phymed.2018.06.015 · DOI
  38. Zhang, 2007, Quantitative analysis of total retronecine esters-type pyrrolizidine alkaloids in plant by high performance liquid chromatography, Anal. Chim. Acta, 605, 94, 10.1016/j.aca.2007.10.021 · DOI

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Metadata

Authors
Chen, Y., Xiong, F., Wang, W., Jiang, K., Ye, X., Deng, G., Wang, C., Yang, L., Xiong, A., & Wang, Z.
Venue
Toxicology Letters
Publisher
Elsevier BV
Published
2020-05
Volume
323
Pages
41-47
ISSN
0378-4274
DOI
10.1016/j.toxlet.2020.01.021
Cited by
23
References
0
Language
en
Licence
Funders
  • Shanghai Municipal Natural Science Foundation
  • National Natural Science Foundation of China

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