Assessment of the oxidative cellular toxicity of a κ-carrageenan oxidative degradation product towards Caco-2 cells

Carrageenan, especially degraded carrageenan (poligeenan) has been known to induce colonic inflammation for a long time. We isolated an oxidized degradation product (κ-CODP) from κ-poligeenan. To explore the toxic potential of this byproduct on human colonic epithelial cells, we examined the oxidative toxicity and pro-inflammatory effects on Caco-2 cells. κ-CODP showed cytotoxicity against Caco-2 cells with concentration higher than 40 μg/mL, and this event was accompanied by the increase of reactive oxygen species (ROS), while the addition of the antioxidant N-acetyl-l-cysteine was able to rescue the fatal effects of κ-CODP on cell growth and apoptosis. The molecular signals following κ-CODP exposure were shown as: the increased secretion of two inflammatory molecules, namely, IL-8 and TNF-α; the activation of NF-κB translocation; and the up-regulation of expression of p-JNK and p-ERK protein. It was suggested that κ-CODP may activate the MAPK signaling pathway and the pro-inflammatory transcription factor NF-κB, leading to phosphorylation of transcription factors that participate in the regulation of cell inflammatory action. These findings suggest that κ-CODP generated during food or medicine processing may influence the cell function of colonic epithelial cell by inducing apoptosis and inflammatory response through ROS production.