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Journal of Lipid Research, Vol. 45, 1418-1428, August 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells

Sònia Roig-Pérez^*, Francesc Guardiola, Miquel Moretó^* and Ruth Ferrer^2,*

^* Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
Departament de Nutrició i Bromatologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain

² To whom correspondence should be addressed. e-mail: rutferrer{at}ub.edu

Dietary enrichment with docosahexaenoic acid (DHA) has numerous beneficial effects on health. However, the intake of high doses of polyunsaturated fatty acids can promote lipid peroxidation and the subsequent propagation of oxygen radicals. The purpose of this study was to evaluate the effect of DHA on lipid peroxidation and tight junction structure and permeability in Caco-2 cell cultures. Moreover, the effects of taurine, a functional ingredient with antioxidant properties, were also tested. Differentiated Caco-2 cell monolayers were maintained in DHA-supplemented conditions with or without added taurine. Incubation with 100 µM DHA increased lipid peroxidation and paracellular permeability, in parallel with a redistribution of the tight junction proteins occludin and ZO-1. Taurine partially prevented all of these effects. The participation of reactive oxygen and nitrogen species in increased paracellular permeability was also examined using various agents that modify the formation of superoxide radical, hydrogen peroxide, nitric oxide, and peroxynitrite.

We conclude that hydrogen peroxide and peroxynitrite may be involved in the DHA-induced increase in paracellular permeability and that the protective role of taurine may be in part related to its capacity to counteract the effects of hydrogen peroxide.

Abbreviations: BHT, butylated hydroxytoluene; CAT, catalase; CPTIO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; DDC, diethyldithiocarbamate; DEF, deferoxamine; DHA, docosahexaenoic acid; GEN, genistein; iNOS, inducible nitric oxide synthase; L-NIL, L-N ⁶-(1-iminoethyl)lysine; mBCl, monochlorobimane; MDA, malondialdehyde; ^•NO, nitric oxide; O₂^•–, superoxide; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; TBA, 2-thiobarbituric acid; TEP, 1,1,3,3-tetraethoxypropane; TER, transepithelial electrical resistance; Tiron, 4,5-dihydroxy-1,3-benzene-disulfonic acid; UR, urate

Supplementary key words docosahexaenoic acid • tight junctions • occludin • ZO-1 • superoxide radical • hydrogen peroxide • nitric oxide • peroxynitrite • reactive oxygen and nitrogen species • free radicals • polyunsaturated fatty acid

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