Article CC BY 4.0
refereed
published

Pyrrolizidine alkaloids induce cell death in human heparg cells in a structure-dependent manner

Affiliation
German Federal Institute for Risk Assessment (BfR), Department 5 Food Safety, Unit 51 Effect-based Analytics and Toxicogenomics, Germany
Glück, Josephin;
Affiliation
Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, Berlin, Germany
Waizenegger, Julia;
Affiliation
German Federal Institute for Risk Assessment (BfR), Department 5 Food Safety, Unit 51 Effect-based Analytics and Toxicogenomics, Germany
Braeuning, Albert;
Affiliation
German Federal Institute for Risk Assessment (BfR), Department 5 Food Safety, Unit 52 Food Toxicology, Germany
Hessel-Pras, Stefanie

Pyrrolizidine alkaloids (PAs) are a group of secondary metabolites produced in various plant species as a defense mechanism against herbivores. PAs consist of a necine base, which is esterified with one or two necine acids. Humans are exposed to PAs by consumption of contaminated food. PA intoxication in humans causes acute and chronic hepatotoxicity. It is considered that enzymatic PA toxification in hepatocytes is structure-dependent. In this study, we aimed to elucidate the induction of PA-induced cell death associated with apoptosis activation. Therefore, 22 structurally different PAs were analyzed concerning the disturbance of cell viability in the metabolically competent human hepatoma cell line HepaRG. The chosen PAs represent the main necine base structures and the different esterification types. Open-chained and cyclic heliotridine-and retronecine-type diesters induced strong cytotoxic effects, while treatment of HepaRG with monoesters did not affect cell viability. For more detailed investigation of apoptosis induction, comprising caspase activation and gene expression analysis, 14 PA representatives were selected. The proapoptotic effects were in line with the potency observed in cell viability studies. In vitro data point towards a strong structure–activity relationship whose effectiveness needs to be investigated in vivo and can then be the basis for a structure-associated risk assessment.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

Use and reproduction: