Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

Yisheng He, Lin Zhu, Jiang Ma, Ge Lin*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

40 Citations (Scopus)

Abstract

Pyrrolizidine alkaloids (PAs) and PA N-oxides are common phytotoxins produced by over 6000 plant species. Humans are frequently exposed to PAs via ingestion of PA-containing herbal products or PA-contaminated foods. PAs require metabolic activation to form pyrrole–protein adducts and pyrrole-DNA adducts which lead to cytotoxicity and genotoxicity. Individual PAs differ in their metabolic activation patterns, which may cause significant difference in toxic potency of different PAs. This review discusses the current knowledge and recent advances of metabolic pathways of different PAs, especially the metabolic activation and metabolism-mediated cytotoxicity and genotoxicity, and the risk evaluation methods of PA exposure. In addition, this review provides perspectives of precision toxicity assessment strategies and biomarker development for the risk control and translational investigations of human intoxication by PAs.

Original languageEnglish
Pages (from-to)1917-1942
Number of pages26
JournalArchives of Toxicology
Volume95
Issue number6
DOIs
Publication statusPublished - Jun 2021

Scopus Subject Areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • Cytotoxicity
  • Genotoxicity
  • Metabolic activation
  • Metabolism-mediated hepatotoxicity
  • Pyrrolizidine alkaloids

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