Toxic or beneficial? Selenoneine in human selenium metabolism

• Applicant: Professorin Dr. Tanja Schwerdtle
• Subject Area: Food Chemistry
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 276311500

Selenium supplementation is widely recommended for a myriad of health benefits, even though the therapeutic window for selenium is narrow and it is unclear which selenium compounds are responsible for the beneficial effects. Mixed outcomes from supplementation trials underline the importance of knowing the form of selenium ingested in order to fully understand its metabolism and any ensuing beneficial or toxic effects. Selenoneine, the selenium analogue of the sulfur-containing compound ergothioneine, a ubiquitous cellular compound with putative antioxidant properties, has recently been discovered as a major selenium compound in marine fish. This joint project between the Institute of Chemistry at the University of Graz and the Institute of Nutritional Science at the University of Potsdam aims to investigate whether selenoneine and its human metabolite Se-methylselenoneine are important compounds in human selenium metabolism, with a significant role in seleniums beneficial health effects. Since neither compound is commercially available, they will be chemically synthesized according to procedures modified from those used to prepare their sulfur analogues. Chemical synthesis will establish a convenient source of the pure compounds in the quantities necessary to delineate their role in human selenium metabolism. The synthesized pure compounds will be used to develop a robust high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC/ICPMS) method for their quantitative determination in complex matrices such as human blood and urine. The HPLC separation must also be compatible with electrospray mass spectrometry to unequivocally prove the presence of selenoneine and Se-methylselenoneine in various matrices. Since selenoneine is easily oxidized, special emphasis will be placed on developing a fast and quantitative reduction/derivatization sample preparation procedure. The synthesized compounds will also be used to elucidate the bioavailability and metabolism as well as the toxicity and potential protective properties of selenoneine and Se-methylselenoneine by performing in vitro studies with mammalian cell cultures (human Caco-2 intestinal cells, human HEPG2 liver cells, LUHMES human neuronal precursor cells, porcine brain capillary endothelial cells and Plexus-Choroideus cells) and first in vivo studies with the nematode C. elegans. At the end of the cell tests, total selenium and selenium metabolites will be determined in cells, C. elegans and cell culture media implementing the developed HPLC/ICPMS method. Results from this project will provide important insights into the potential protective properties, toxicity and human metabolism of these novel forms of the essential trace element selenium, and help to shed light on their contribution to seleniums ascribed health benefits.

• DFG Programme: Research Grants
• International Connection: Austria, USA
• Cooperation Partners: Professor Michael Aschner, Ph.D.; Professorin Dr. Doris Kuehnelt