Pyrrolizidine Alkaloids and Hepatic Toxicity

Pyrrolizidine alkaloids (PAs) are a class of plant-derived secondary metabolites found in certain Asteraceae, Boraginaceae and Fabaceae species worldwide. These compounds serve as natural defence agents against herbivores, yet their hepatotoxic and genotoxic properties pose significant health hazards to humans and livestock. Upon ingestion, PAs undergo metabolic activation predominantly by hepatic cytochrome P450 enzymes, yielding reactive pyrrolic metabolites that can alkylate cellular macromolecules, disrupt mitochondrial function and provoke oxidative stress. Clinically, exposure to high PA doses manifests as hepatic sinusoidal obstruction syndrome or veno-occlusive disease, while chronic low-level intake increases the risk of fibrosis, cirrhosis and hepatocellular carcinoma. PA contamination arises in foodstuffs such as herbal infusions, honey, cereals, spices and dietary supplements, often resulting from co-harvesting of PA-producing weeds. Regulatory bodies have set maximum limits for several regulated PAs, yet emerging analytical techniques continue to reveal previously unmonitored structures, emphasising the global need for robust surveillance, standardised extraction protocols and refined risk assessment. Integrative approaches that combine high-resolution analytics, in vitro genotoxicity assays, physiologically based kinetic modelling and benchmark dose determinations are paving the way for expeditious evaluation of toxicity and potency ranking, thereby informing policy and improving food safety standards worldwide.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Pyrrolizidine Alkaloids and Hepatic Toxicity publication trend

The graph below shows the total number of articles in pyrrolizidine alkaloids and hepatic toxicity across all publications each year (not limited to Nature Index journals).

Technical terms

Pyrrolizidine alkaloids: A group of hepatotoxic secondary plant metabolites characterised by a necine base linked to necic acids, notable for their reactive dehydro-pyrrolizidine metabolites.

Cytochrome P450: A family of haem-containing enzymes in the liver responsible for oxidative metabolism and bioactivation of many xenobiotics, including PAs.

Genotoxicity: The property of a compound to damage genetic material, often assessed by assays measuring DNA strand breaks or chromosomal alterations.

Benchmark dose modelling: A quantitative risk assessment technique that fits dose–response data to derive exposure levels associated with predefined adverse effects.

Physiologically based kinetic (PBK) modelling: A mathematical modelling approach that uses physiological and biochemical parameters to predict the absorption, distribution, metabolism and excretion of chemicals in humans or animals.

References

1. Target screening method for the quantitative determination of 118 pyrrolizidine alkaloids in food supplements, herbal infusions, honey and teas by liquid chromatography coupled to quadrupole orbitrap mass spectrometry. Food Chemistry (2023).
2. Potency ranking of pyrrolizidine alkaloids in metabolically competent human liver cancer cells and primary human hepatocytes using a genotoxicity test battery. Archives of Toxicology (2023).
3. Use of an in vitro–in silico testing strategy to predict inter-species and inter-ethnic human differences in liver toxicity of the pyrrolizidine alkaloids lasiocarpine and riddelliine. Archives of Toxicology (2019).