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Titolo:
Replenishment of glutathione levels improves mucosal function in experimental acute colitis
Autore:
Ardite, E; Sans, M; Panes, J; Romero, FJ; Pique, JM; Fernandez-Checa, JC;
Indirizzi:
CSIC, Inst Invest Biomed August Bi Suner, Inst Malalties Digest, E-08036 Barcelona, Spain CSIC Barcelona Spain E-08036 Malalties Digest, E-08036 Barcelona, Spain Hosp Clin & Prov Barcelona, Liver Unit, E-08036 Barcelona, Spain Hosp Clin& Prov Barcelona Barcelona Spain E-08036 8036 Barcelona, Spain Univ Valencia, Sch Med & Dent, Dept Physiol, Expt Toxicol & Neurotoxicol Unit, Valencia, Spain Univ Valencia Valencia Spain xicol & Neurotoxicol Unit, Valencia, Spain
Titolo Testata:
LABORATORY INVESTIGATION
fascicolo: 5, volume: 80, anno: 2000,
pagine: 735 - 744
SICI:
0023-6837(200005)80:5<735:ROGLIM>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
INFLAMMATORY BOWEL-DISEASE; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; TRINITROBENZENE SULFONIC-ACID; PLATELET-ACTIVATING FACTOR; ELECTRON-TRANSPORT CHAIN; HEAVY SUBUNIT CHAIN; TRANSCRIPTIONAL REGULATION; OXIDATIVE STRESS; EPITHELIAL-CELLS; RAT MODEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Fernandez-Checa, JC CSIC, Inst Invest Biomed August Bi Suner, Inst Malalties Digest, Villarroel 170, E-08036 Barcelona, Spain CSIC Villarroel 170 Barcelona Spain E-08036 na, Spain
Citazione:
E. Ardite et al., "Replenishment of glutathione levels improves mucosal function in experimental acute colitis", LAB INV, 80(5), 2000, pp. 735-744

Abstract

Because reactive oxygen species (ROS) have been implicated as mediators ofinflammatory bowel disease (IBD), the purpose of the present work was to determine the functional role of mucosal GSH in the trinitrobenzenesulfonic acid in 50% ethanol (TNBS+ethanol)-induced colitis in rats. Mucosal sampleswere taken to evaluate the temporal relationship between the extent of injury, the levels of glutathione (GSH) during acute colitis induced by TNBS+ethanol, and the effect of N-acetylcysteine (NAC) administration. In vitro assays revealed the interaction of TNBS with GSH leading to the almost instantaneous disappearance of GSH, while the reductive metabolism of TNBS by GSSG reductase generated ROS. Mucosal samples from TNBS+ethanol-treated rats indicated a direct correlation between GSH depletion and injury detected assoon as 30 minutes after TNBS+ethanol administration that persisted 24 hours post treatment. Although, short term depletion of mucosal GSH per se by diethylmaleate did not result in mucosal injury, the oral administration ofNAC (40 mM) 4 hours after TNBS+ethanol treatment increased GSH stores (2-fold), decreasing the extent of mucosal injury (60-70%) examined at 24 hourspost treatment. However, an equimolar dose of dithiothreitol failed to increase GSH levels and protect mucosa from TNBS+ethanol-induced injury. Interestingly, GSH levels in TNBS+ethanol-treated rats recovered by 1-2 weeks. an effect that was accounted for by an increase of gamma-glutamylcysteine synthetase (gamma-GCS) activity due to an induction of gamma-GCS-heavy subunit chain mRNA. Thus, TNBS promotes two independent mechanisms of injury, GSHdepletion and ROS generation, both being required for the manifestation ofmucosal injury as GSH limitation renders intestine susceptible to the TNBS-induced ROS overgeneration. Accordingly, in vivo administration of NAC attenuates the acute colitis through increased mucosal GSH levels, suggesting that GSH precursors may be of relevance in the acute relapse of IBD.

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Documento generato il 25/01/20 alle ore 03:18:43