Taurodeoxycholate-induced intestinal injury is modulated by oxidative stress-dependent pre-conditioning like mechanisms

Mechanisms by which hydrophobic bile salts cause tissue changes below their critical micellar concentration (CMC, 1-2 mM) and above (4-8 mM) remain poorly understood. In this study, rat colonic mucosa was exposed to different concentrations of taurodeoxycholate (TDC), t-butyl-hydroperoxide (t-BH) or glutathione ester with or without pre-incubation with 2 mM TDC. Exposure to 2 mM TDC was associated with 10% higher tissue levels of total glutathione (GSH, basal values: 33.7 ± 3.3 nmol/mg prot). With TDC 8 mM, GSH decreased to 16.4 ± 2.3 nmol/mg prot (P < 0.05), oxidized glutathione (GSSG) increased by 60% (P < 0.05), glutathione peroxidase (GSH-Px) and reductase activities were threefold increased, protein carbonyls fourfold increased, protein sulfhydrils decreased by 78%, lactate dehydrogenase (LDH) and GSSG release in the incubation medium were sixfold higher. In 2 mM TDC pre-treated tissues, the subsequent incubation with 8 mM TDC induced a lower loss of tissue GSH, and a lower release of LDH and GSSG. Pre-incubation with 2 mM TDC partly protected against t-BH toxicity, while glutathione ester protected against 8 mM TDC toxicity. In conclusion, TDC exposure causes opposite effects depending on CMC: induction of antioxidant protective systems including glutathione system (pre-conditioning effect) was observed with TDC below CMC, oxidative damages pointing to decreased mucosal detoxification potential with above CMC.