Marine toxins, food safety threats and One Health approach: cytotoxicity and intestinal bioavailability of okadaic acid in the porcine IPEC-J2 intestinal cell line

In the context of One Health approach, which recognizes the interconnection between human, animal, and environmental health, marine biotoxins pose an increasing threat to food safety. Among these ones, okadaic acid (OA), a potent lipophilic toxin produced by marine dinoflagellates, is responsible for Diarrhetic Shellfish Poisoning (DSP) in humans through the consumption of contaminated shellfish. OA primarily acts by inhibiting serine/threonine protein phosphatases, leading to alterations in cell viability and intestinal epithelial homeostasis. This study aimed at evaluating the cytotoxic effects of OA on a porcine intestinal epithelial cell line (IPEC-J2), which represent a commonly used comparative in vitro model due to its close morphological and functional similarities with human enterocytes. OA cytotoxicity was assessed by using Alamar Blue and Neutral Red Uptake assays, which allowed the determination of IC₅₀ values across different exposure times (24 and 48h). Additionally, the integrity of the epithelial barrier was evaluated either measuring the transepithelial electrical resistance (TEER) than changes in paracellular permeability using the Lucifer Yellow (LY) assay. The results demonstrate that OA induces cytotoxic effects in a dose- and time-dependent manner, with notable impairment of both metabolic activity and lysosomal integrity. However, TEER and LY permeability results did not show significant differences between control cells (treated with DMSO 0.1%) and cells exposed to 5 nM (non-toxic concentration), 20 nM (subtoxic concentration), and 80 nM (IC₅₀ of OA in IPEC-J2 cells) These preliminary findings contribute to the understanding of OA mechanisms of toxicity and support the relevance of IPEC-J2 cells as a model for evaluating foodborne toxin-induced intestinal damage, with implications for public health risk assessment.