Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

Yisheng He; Lin Zhu; Jiang Ma; Ge Lin

doi:10.1007/s00204-021-03060-w

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

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

^*Corresponding author for this work

Centre for Chinese Herbal Medicine Drug Development Limited

Research output: Contribution to journal › Review article › peer-review

43 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 language	English
Pages (from-to)	1917-1942
Number of pages	26
Journal	Archives of Toxicology
Volume	95
Issue number	6
DOIs	https://doi.org/10.1007/s00204-021-03060-w
Publication status	Published - 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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10.1007/s00204-021-03060-w

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title = "Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids",

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.",

keywords = "Cytotoxicity, Genotoxicity, Metabolic activation, Metabolism-mediated hepatotoxicity, Pyrrolizidine alkaloids",

author = "Yisheng He and Lin Zhu and Jiang Ma and Ge Lin",

note = "Funding Information: The work was supported by Research Grants Council of Hong Kong Special Administrative Region (GRF Project nos. 14111816, 14106318, 14107719 and 14106120). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2021",

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AU - He, Yisheng

AU - Zhu, Lin

AU - Ma, Jiang

AU - Lin, Ge

N1 - Funding Information: The work was supported by Research Grants Council of Hong Kong Special Administrative Region (GRF Project nos. 14111816, 14106318, 14107719 and 14106120). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

KW - Cytotoxicity

KW - Genotoxicity

KW - Metabolic activation

KW - Metabolism-mediated hepatotoxicity

KW - Pyrrolizidine alkaloids

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U2 - 10.1007/s00204-021-03060-w

DO - 10.1007/s00204-021-03060-w

M3 - Review article

C2 - 34003343

AN - SCOPUS:85106247596

SN - 0340-5761

VL - 95

SP - 1917

EP - 1942

JO - Archives of Toxicology

JF - Archives of Toxicology

IS - 6

ER -

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

Abstract

Scopus Subject Areas

User-Defined Keywords

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