In vitro toxicological characterization of two arsenosugars and their metabolites
Article first published online: 8 APR 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 7, pages 1270–1282, July 2013
How to Cite
Leffers, L., Ebert, F., Taleshi, M. S., Francesconi, K. A. and Schwerdtle, T. (2013), In vitro toxicological characterization of two arsenosugars and their metabolites. Mol. Nutr. Food Res., 57: 1270–1282. doi: 10.1002/mnfr.201200821
- Issue published online: 1 JUL 2013
- Article first published online: 8 APR 2013
- Manuscript Accepted: 4 FEB 2013
- Manuscript Revised: 31 JAN 2013
- Manuscript Received: 12 DEC 2012
- DFG. Grant Number: SCHW 903/4-1
- Austrian Science Fund (FWF). Grant Number: I550-N17
- Graduate School of Chemistry
- Cellular and intestinal bioavailability;
- Cellular toxicity;
- Marine food
In their recently published Scientific Opinion on Arsenic in Food, the European Food Safety Authority concluded that a risk assessment for arsenosugars is currently not possible, largely because of the lack of relevant toxicological data. To address this issue, we carried out a toxicological in vitro characterization of two arsenosugars and six arsenosugar metabolites.
Methods and results
The highly pure synthesized arsenosugars, DMAV-sugar-glycerol and DMAV-sugar-sulfate, investigated in this study, as well as four metabolites, oxo-dimethylarsenoacetic acid (oxo-DMAAV), oxo-dimethylarsenoethanol (oxo-DMAEV), thio-DMAAV and thio-DMAEV, exerted neither cytotoxicity nor genotoxicity up to 500 μM exposure in cultured human bladder cells. However, two arsenosugar metabolites, namely dimethyl-arsinic acid (DMAV) and thio-dimethylarsinic acid (thio-DMAV), were toxic to the cells; thio-DMAV was even slightly more cytotoxic than arsenite. Additionally, intestinal bioavailability of the arsenosugars was assessed applying the Caco-2 intestinal barrier model. The observed low, but significant transfer rates of the arsenosugars across the barrier model provide further evidence that arsenosugars are intestinally bioavailable.
In a cellular system that metabolizes arsenosugars, cellular toxicity likely arises. Thus, in strong contrast to arsenobetaine, arsenosugars cannot be categorized as nontoxic for humans and a risk to human health cannot be excluded.