In vitro cytotoxic effect of wheat gliadin-derived peptides on the Caco-2 intestinal cell line is associated with intracellular oxidative imbalance: implications for coeliac disease

Coeliac disease (CD) is an inflammatory disorder of the upper small intesti ne in which gluten acts as an essential factor in its pathogenesis. Althoug h it is generally accepted that cereal protein activation of the immune sys tem is involved in CD progression, a non-immunomediated cytotoxic activity of gliadin-derived peptides on the jejunal/duodenal tract cannot be exclude d. In this work, considering that (a) little has been reported about the in tracellular metabolic events associated with gliadin toxicity, and (b) an i mportant role for free radicals in a number of gastrointestinal disease has been demonstrated, we investigated the in vitro effects of gliadin-derived peptides on redox metabolism of Caco-2 intestinal cells during a kinetic s tudy in which cells were exposed to peptic-tryptic digest of bread wheal up to 48 h. We found that the antiproliferative effects displayed by gliadin exposure was associated with intracellular oxidative imbalance, characteris ed by an increased presence of lipid peroxides, an augmented oxidised (GSSC )/reduced (GSH) glutathione ratio and a loss in protein-bound sulfhydryl gr oups. Significant structural perturbations of the cell plasma membrane were also detected. Additional experiments performed by using the specific GSH- depleting agent buthionine sulfoximine provide evidence that the extent of gliadin-induced cell growth arrest critically depends upon the 'basal' redo x profile of the enterocytes. On the whole, these findings seem to suggest that, besides the adoption of a strictly gluten-free diet, the possibility for an adjuvant therapy with antioxidants may be considered for CD patients . (C) 1999 Elsevier Science B.V. All rights reserved.