Deoxynivalenol (DON) is well-known enteropathogenic mycotoxin which can alter intestinal barrier functions. Consistently, Ochratoxin A (OTA) ingestion has been found to induce intestinal injuries, including inflammation and diarrhea. However, little is known whether OTA aggravates DON-induced toxicity. This study is designed to explore the effects of OTA on DON-induced intestinal barrier function and involved mechanism. Our results showed either DON or OTA could disrupt intestinal barrier function in a time- and dose-dependent manner, as demonstrated by decreased transepithelial electrical resistance (TEER) and increased paracellular permeability to 4 kDa dextran. However, to eliminate the involvement of cell death, nonlethal concentrations of DON and OTA were used in following experiments. The nontoxic concentration of OTA was observed to aggravate DON-induced intestinal barrier dysfunction, accompanied with tight junction disruption (Claudin-3 and Claudin-4). Moreover, nontoxic concentrations of OTA aggravated DON-induced up-regulation of pro-inflammatory cytokines expression and activated nuclear factor-κB (NF-κB) in IPEC-J2 cells. Adding NF-κB inhibitor (PDTC) alleviated the aggravating effects of nontoxic concentrations of OTA on DON-induced intestinal barrier dysfunction and inflammation. These findings indicate that nontoxic concentrations of OTA promoted DON-induced barrier dysfunction via NF-κB signaling pathway. Our experiment suggests that exposure to nontoxic concentrations of toxins also poses potentially harmful effects.
Keywords: Barrier function; Deoxynivalenol; Nuclear factor-κB; Ochratoxin A; Tight junction.
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