UPLC-MS/MS analysis of ochratoxin A metabolites produced by Caco-2 and HepG2 cells in a co-culture system

González Arias, Cyndia A.; Marín Sillué, Sònia; Rojas-García, A. E.; Sanchís Almenar, Vicente; Ramos Girona, Antonio J.

doi:https://doi.org/10.1016/j.fct.2017.09.011

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Issue date

2017-09-19

Author

González Arias, Cyndia A.

Marín Sillué, Sònia

Rojas-García, A. E.

Sanchís Almenar, Vicente

Ramos Girona, Antonio J.

Suggested citation

González Arias, Cyndia A.; Marín Sillué, Sònia; Rojas-García, A. E.; Sanchís Almenar, Vicente; Ramos Girona, Antonio J.; . (2017) . UPLC-MS/MS analysis of ochratoxin A metabolites produced by Caco-2 and HepG2 cells in a co-culture system. Food and Chemical Toxicology, 2017, vol. 109, p. 333-340. https://doi.org/10.1016/j.fct.2017.09.011.

Abstract

Ochatoxin A (OTA) is one of the most important mycotoxins based on its toxicity. The oral route is the main gateway of entry of OTA into the human body, and specialized epithelial cells constitute the first barrier. The present study investigated the in vitro cytotoxic effect of OTA (5, 15 and 45 μM)

and production of OTA metabolities in Caco-2 and HepG2 cells using a co-culture Transwell System to mimic the passage through the intestinal epithelium and hepatic metabolism. The results derived from MTS cell viability assays and transepithelial electrical resistance measurements showed that OTA was slightly cytotoxic at the lowest concentration at 3 h, but significant toxicity was observed at all concentrations at 24 h. OTA metabolites generated in this co-culture were ochratoxin B (OTB), OTA methyl ester, OTA ethyl ester and the OTA glutathione conjugate (OTA-GSH). OTA methyl ester was the major metabolite found in both Caco-2 and HepG2 cells after all treatments. Our results showed that OTA can cause cell damage through several mechanisms and that the OTA exposure time is more important that the dosage in in vitro studies. OTA methyl ester is proposed as an OTA exposure biomarker, although future studies should be conducted.

URI

http://hdl.handle.net/10459.1/62976

DOI

https://doi.org/10.1016/j.fct.2017.09.011

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Food and Chemical Toxicology, 2017, vol. 109, p. 333-340

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