A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin A in human intestinal cells

Abstract

Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.

Highlights: Patulin (PAT) and ochratoxin A (OTA) combined effects were studied in Caco-2 cells; To ascertain putative interactive effects conceptual mathematical models were used; Cytotoxicity data revealed a dose-ratio deviation; Genotoxicity results showed interactive DNA damaging effects; Gastrointestinal barrier integrity effects suggested a synergism at low levels of both mycotoxins.