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, 1–2mM) and above (4–8mM) 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 2mM TDC. Exposure to 2mM TDC was associated with 10% higher tissue levels of total glutathione (GSH, basal values: 33.7±3.3 nmol/mg prot). With TDC 8mM, 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 activitieswere 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 2mM TDC pre-treated tissues, the subsequent incubation with 8mM TDC induced a lower loss of tissue GSH, and a lower release of LDH and GSSG. Preincubation with 2mMTDC partly protected against t-BH toxicity, while glutathione ester protected against 8mM 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.