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Imprint
Development of a hepatic in vitro test system for the sensitive detection of pyrrolizidine alka-loids
Project
Project code: BfR-LMS-08-1322-454
Contract period: 01.04.2010
- 31.12.2011
Purpose of research: Applied research
Unsaturated pyrrolizidine alkaloids (PA) belong to the most toxic compounds; more than 400 PAs have been described in a wide range of plants. They are also found in Senecio vulgaris L. PAs are toxic to humans and animals. Acute PA poisoning via food contamination causes severe damage to the liver; long-term, sub-lethal doses may cause cumulative damage or cancer. Animal studies revealed that PA are carcinogenic. Mutagenicity of PA was observed in several in vitro and in vivo test systems.The toxicity of these compounds is associated with enzymatic reactions by enzymes domi-nantly expressed in liver. To detect contaminations of PA in food/plant extracts classical analytical methods are used until now. However, the mode of actions of PA to generate hepatotoxicity is not identified yet.This study was planned for 2 years. In the year 2010 we investigated the influence of se-neciphyllin, senecionin, retrorsin on cellular parameters like cytotoyic effects, induction of apoptosis, proliferation, ATP content in the hepatocarcinoma cell line HepG2 as well as the mechanism of the absorption process for senecionin and its N-oxide in a model system for the human gastro-intestinal barrier (Caco-2 cell line). The characterization of the absorption should be continued in 2011. Furthermore, the cellular effects of naturally occurring N-oxides of seneciphyllin, senecionin, retrorsin should be analyzed in HepG2 cells. Addition-ally the formation of phase I and phase II conjugates and the mode of action of PA in pri-mary human hepatocytes which should be investigated by whole genome µ-array analysis are in our focus. These studies should elucidate the mode of action of the strong hepatotox-icity in humans including the identification of specific biomarkers which can further be used for the elucidation of an in vitro test system.
Section overview
Subjects
- Toxicology
