Differential copper transport and redox responses in Caco-2 and mucus-producing intestinal epithelial coculture models.

Copper is an essential trace element whose intestinal handling and associated cellular responses are tightly regulated. However, the role of the intestinal mucus layer in these processes remains insufficiently characterized. In this study, epithelial responses to ionic copper (Cu²⁺) and histidine-complexed copper were investigated using a conventional Caco-2 monoculture and a mucus-producing Caco-2/HT29-MTX coculture model. Under low-level copper conditions reflecting dietary concentrations, cell-associated copper levels, transepithelial copper transport, and redox-related cellular responses were assessed in parallel. Both copper forms resulted in comparable cell-associated copper levels and basolateral copper concentrations in mucus-free and mucus-containing models, indicating that overall copper uptake and transport were similar between the two models under the conditions examined. In contrast, redox responses differed between models. The mucus-producing coculture exhibited lower baseline glutathione peroxidase activity and malondialdehyde levels, together with moderated and temporally delayed oxidative responses, compared with the Caco-2 monoculture. Responses to ionic and histidine-complexed copper also tended to be more similar in the coculture model. These findings indicate that comparable copper uptake and transport can be accompanied by distinct redox response patterns in different intestinal epithelial models and suggest that a mucus-producing epithelial interface may influence downstream cellular responses to copper.