Combined effects of cadmium and ochratoxin A on intestinal barrier dysfunction in human Caco-2 cells and pig small intestinal epithelial cells

Hazardous chemicals are commonly found in cereals and cereal-based products. However, most studies focus on the individual effects of these mycotoxins or metals, rather than their combined toxicity. The main objective of this study was to evaluate the combined effects of cadmium (Cd) and ochratoxin A (OTA) on intestinal barrier integrity using Caco-2 cells and pig small intestinal epithelial (PSI) cells as models of intestinal epithelial cells and to measure alterations in cell survival and barrier integrity. The combined effects on cell viability were assessed in terms of a combination of index values. These findings showed that co-exposure to Cd + OTA had synergistic effects on Caco-2 and PSI cells at 25%, 50%, and 75% inhibitory concentrations (IC₂₅, IC₅₀, and IC₇₅, respectively) against cell viability. Individual Cd and OTA treatments had no effect, but combined Cd + OTA exposure resulted in synergistic down-regulation of paracellular apical junction complex proteins, such as claudin-1, occludin, and E-cadherin. The current findings indicate that the combined effects of OTA + Cd may have consequences at the gut level, which should not be underestimated when considering their risk to human health. Graphical abstract: [Figure not available: see fulltext.].