Planta Med 2021; 87(15): 1314
DOI: 10.1055/s-0041-1736986
Abstracts
8. Poster Contributions
8.9 Recent Advances in Medicinal Plant and Natural Product Research

Studies on mechanism of genotoxicity of selected pyrrolizidine alkaloids in HepG2 cells

NS A Hadi
1   Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany
2   School of Health and Human Sciences, Pwani University, Kilifi, Kenya
,
E E Bankoglu
1   Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany
,
O Kelber
3   R&D, Phytomedicines Supply and Development Center, Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
,
H Sievers
4   PhytoLab GmbH & Co. KG, Vestenbergsgreuth, Germany
,
H Stopper
1   Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany
› Author Affiliations
OK is employee of Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany, HS of Phytolab GmbH & Co. KG, Vesterbergsgreuth, Germany. The study has been financially supported by Phytolab GmbH & Co. KG and Steigerwald Arzneimittelwerk GmbH.
› Further Information
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Introduction Pyrrolizidine alkaloids (PAs) have been discovered in food, food supplements and herbs/spices. Certain PAs are hepatotoxic and genotoxic and are potentially harmful to humans. Here we investigated the chemical structure effect relationship of several genotoxic PAs.

Methodology The genotoxicity of PAs of different esterification types, such as europine, retrorsine and lasiocarpine, was determined in HepG2 cells using the cytokinesis-block micronucleus (CBMN) assay. DNA-crosslinking activity of different PA-types was investigated using a modified comet assay. The role of metabolic enzymes such as cytochrome P450s was investigated by using the inhibitor ketoconazole.

Results An increase of micronucleus formation was found with all tested PAs of different chemical structure. The lowest concentrations at which significant induction of micronuclei were detected were 3.2µM for lasiocarpine (open diester type), 32µM for retrorsine (cyclic diester type) and 100µM for europine (monoester type). In the modified crosslink comet assay, the diester type PAs reduced tail formation after hydrogen peroxide treatment, while an equimolar concentration of the monoester europine did not significantly reduce DNA migration. In addition, micronucleus induction by lasiocarpine was abolished after pre-treatment with the cytochrome P450 inhibitor ketoconazole [1].

Conclusion The results strengthen the hypothesis that the genotoxicic potential depends on the ester type of the PAs with the open diester PA-type being the most potent while the monoester PA-type being the least potent. In the modified comet assay, the crosslinking activity was also related to the ester type of PAs.



Publication History

Article published online:
13 December 2021

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  • References

  • 1 Hadi et al., Mutation Research/Genetic Toxicology and Environmental Mutagenesis 861 (2021): 503305
    PubMed