Literature DB >> 26761716

7-cysteine-pyrrole conjugate: A new potential DNA reactive metabolite of pyrrolizidine alkaloids.

Xiaobo He1, Qingsu Xia1, Liang Ma1, Peter P Fu1.   

Abstract

Pyrrolizidine alkaloids (PAs) require metabolic activation to exert cytotoxicity, genotoxicity, and tumorigenicity. We previously reported that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts are responsible for PA-induced liver tumor formation in rats. In this study, we determined that metabolism of riddelliine and monocrotaline by human or rat liver microsomes produced 7-cysteine-DHP and DHP. The metabolism of 7-glutathionyl-DHP by human and rat liver microsomes also generated 7-cysteine-DHP. Further, reaction of 7-cysteine-DHP with calf thymus DNA in aqueous solution yielded the described DHP-derived DNA adducts. This study represents the first report that 7-cysteine-DHP is a new PA metabolite that can lead to DNA adduct formation.

Entities:  

Keywords:  7-cysteine-DHP adducts; DNA adduct formation; Pyrrolizidine alkaloid; metabolic activation

Mesh：

Substances：

Year:  2016        PMID： 26761716     DOI： 10.1080/10590501.2015.1135593

Source DB:  PubMed          Journal:  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev        ISSN： 1059-0501            Impact factor:   3.781


  6 in total

1.  Developing urinary pyrrole-amino acid adducts as non-invasive biomarkers for identifying pyrrolizidine alkaloids-induced liver injury in human.

Authors:  Lin Zhu; Chunyuan Zhang; Wei Zhang; Qingsu Xia; Jiang Ma; Xin He; Yisheng He; Peter P Fu; Wei Jia; Yuzheng Zhuge; Ge Lin
Journal:  Arch Toxicol       Date:  2021-08-14       Impact factor: 6.168

2.  In vitro biotransformation of pyrrolizidine alkaloids in different species. Part I: Microsomal degradation.

Authors:  Franziska Kolrep; Jorge Numata; Carsten Kneuer; Angelika Preiss-Weigert; Monika Lahrssen-Wiederholt; Dieter Schrenk; Anja These
Journal:  Arch Toxicol       Date:  2017-11-16       Impact factor: 5.153

Review 3.  Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450.

Authors:  Christopher Trent Brewer; Taosheng Chen
Journal:  Int J Mol Sci       Date:  2017-11-08       Impact factor: 5.923

4.  7-N-Acetylcysteine-pyrrole conjugate-A potent DNA reactive metabolite of pyrrolizidine alkaloids.

Authors:  Xiaobo He; Liang Ma; Qingsu Xia; Peter P Fu
Journal:  J Food Drug Anal       Date:  2016-09-10       Impact factor: 6.157

Review 5.  Pyrrole-protein adducts - A biomarker of pyrrolizidine alkaloid-induced hepatotoxicity.

Authors:  Jiang Ma; Qingsu Xia; Peter P Fu; Ge Lin
Journal:  J Food Drug Anal       Date:  2018-06-14       Impact factor: 6.157

6.  Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides.

Authors:  Xiaobo He; Qingsu Xia; Kellie Woodling; Ge Lin; Peter P Fu
Journal:  J Food Drug Anal       Date:  2017-09-19       Impact factor: 6.157
  6 in total

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