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 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 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. Pre-incubation with 2mM TDC 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.
Portincasa
Piero
P
Clinica Medica A. Murri, Department of Internal and Public Medicine, University of Bari, Piazza G. Cesare, 11-70124 Bari, Italy. p.portincasa@semeiotica.uniba.it
Grattagliano
Ignazio
I
Petruzzelli
Michele
M
Moschetta
Antonio
A
Debellis
Lucantonio
L
Palasciano
Giuseppe
G
D000818:Animals; D002756:Cholagogues and Choleretics / Q000737:chemistry / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008823:Micelles; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013657:Taurodeoxycholic Acid / Q000737:chemistry / Q000633:toxicity*
D002756:Cholagogues and Choleretics; D008823:Micelles; D013438:Sulfhydryl Compounds; D013657:Taurodeoxycholic Acid; D007770:L-Lactate Dehydrogenase; D005978:Glutathione