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How do pyrrolizidine alkaloids damage the liver?

18/2016, 27.05.2016

Research project at the BfR promoted by DFG examines the mechanisms of action of pyrrolizidine alkaloids in the human body

Pyrrolizidine alkaloids are natural ingredients formed by many different plants as protection against pests. As tests conducted by the German Federal Institute for Risk Assessment and examination authorities of the federal states show, pyrrolizidine alkaloids can occur as contaminants in foods such as tea, salad mixes and honey, sometimes in high concentrations. Due to their liver-damaging and possibly carcinogenic effects, however, they are not desired here. Little is currently known about the intake routes, distribution and mechanism of action of pyrrolizidine alkaloids in the human body. In the research project "Identification of the structure-dependent toxicity of hepatotoxic pyrrolizidine alkaloids" sponsored by the German Research Foundation (DFG), scientists at the German Federal Institute for Risk Assessment (BfR) are examining the ways in which the various pyrrolizidine alkaloids are ingested by the body, how they are transported inside the body to the various target cells and in which way they damage the cells and organs. "Research into the precise mechanisms of action of food contaminants of this kind is an important contribution to the assessment of the health risk posed by these substances," says Professor Dr. Dr. Andreas Hensel, President of the German Federal Institute for Risk Assessment. "When people are exposed to pyrrolizidine alkaloids, we can estimate the health effects more precisely thanks to the knowledge acquired". The sponsoring of the research project by the DFG underscores the fact that the BfR is attempting to close major knowledge gaps here and lay important foundations for consumer health protection, both of which will help to minimise health risks for the consumer.

The interest of the BfR scientists focuses on the molecular mechanisms of intake and toxicity of pyrrolizidine alkaloids. The main goal here is to identify which of the numerous compounds of this substance group are damaging to the organism and which toxic mechanisms are responsible for this. In two research projects already funded and conducted by the BfR, it could be proven using methods of molecular toxicology that the body has a transport system which transports at least some pyrrolizidine alkaloids out of the body, depending on their specific chemical structure. For this reason, these specific compounds presumably have lower damage potential. It was also shown in these tests that the toxic pyrrolizidine alkaloids affect liver cells in different ways. They disturb fatty acid metabolism and bile acid secretion, for instance. On the basis of this BfR-internal research, the DFG has now approved a follow-on research project scheduled to last for three years. Under the title "Identification of the structure-dependent toxicity of hepatotoxic pyrrolizidine alkaloids", structure-specific differences of the various pyrrolizidine alkaloids are to be determined and the resultant differences in the toxic effect further examined. The focus of this project is on intake into the body and the different molecular effects on the liver depending on the structure of the pyrrolizidine alkaloids. In-vitro cell culture models are to be used her on the one hand while on the other, the toxic effect of the pyrrolizidine alkaloids on mouse liver is also to be observed in real time using modern imaging methods. The molecular toxicity mechanisms on certain liver cell types are to be identified by means of these analyses. The study is intended to contribute towards enabling a more precise and complete assessment of the health risk of pyrrolizidine alkaloids and help to minimise the risk of health-damaging effects for humans.

The first results of the BfR research on the effect of pyrrolizidine alkaloids in the body were published in the magazines "Molecular Nutrition & Food Research" 2014 May;58(5):995-1004 (http://www.ncbi.nlm.nih.gov/pubmed/24375927)

and "Toxicology in Vitro" 2015 Oct;29(7):1669-82 (http://www.ncbi.nlm.nih.gov/pubmed/26100227).

About the BfR

The German Federal Institute for Risk Assessment (BfR) is a scientific institution within the portfolio of the Federal Ministry of Food and Agriculture (BMEL) in Germany. It advises the Federal Government and Federal Laender on questions of food, chemical and product safety. The BfR conducts its own research on topics that are closely linked to its assessment tasks.

This text version is a translation of the original German text which is the only legally binding version.

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