Possible Mechanisms Of The Copper Effect On Intestinal Tight Junctions

5.1. Copper and Oxidative Stress

Like other transition metals, copper is able to produce reactive oxygen species in aqueous solutions and hence to produce oxidative damage to the cell. The toxic oxygen metabolites have many intracellular effects, including enhanced lipid peroxidation, DNA damage, and altered calcium and sulfhydryl homeostasis (71).

To test whether the effect of copper ions on tight-junction permeability was mediated by the production of reactive oxygen species (ROS) we used a set of antioxidants (mannitol, dimethylsulfox-ide, and a soluble derivative of vitamin E). None of these ROS scavengers, added during the treatment of Caco-2 cells with 30 | M CuCl2 at pH 6.0 for 4 h in the AP compartment, was able to counteract the effect of copper ions on the tight junctions as measured by 3H-mannitol passage and by TEER measure (50).

It had previously been demonstrated that hydrogen peroxide was able to increase paracellular permeability in Caco-2 cells via activation of protein tyrosine phosphorylation (72). In a more recent work, this group further demonstrated that hydrogen peroxide but not superoxide anions nor the

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