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Query: UMLS:C0021390 (
inflammatory bowel disease
)
23,302
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Because reactive oxygen species (ROS) have been implicated as mediators of
inflammatory 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 samples were 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 as soon 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 of NAC (40 mM) 4 hours after TNBS+ethanol treatment increased GSH stores (2-fold), decreasing the extent of mucosal injury (60-70%) examined at 24 hours post 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, GSH depletion and ROS generation, both being required for the manifestation of mucosal 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
.
...
PMID:Replenishment of glutathione levels improves mucosal function in experimental acute colitis. 1083 Jul 84
Glutathione is a nonenzymatic antioxidant synthesized by most animal cells and is depleted in
inflammatory bowel disease
. The effects of glutathione depletion on intestinal histology and inhibitory neurochemicals was examined in a mouse model. Glutathione depletion in A/J mice involved inhibition of
gamma-glutamylcysteine synthetase
using L-buthionine-(S,R)-sulfoximine (BSO) for 10 days. Ileum and colon were obtained from saline-control mice, BSO-treated mice, and BSO-treated mice receiving ascorbate or glutathione monoethylester. Glutathione, lipid peroxides, and nicotineamide adenine dinucleotide phosphate diaphorase activity were measured by colorimetric assays. Vasoactive intestinal peptide was measured by radioimmunoassay. Glutathione depletion induced enlargement of mucosal-submucosal lymphoid aggregates without germinal centers in ileum and colon. These aggregates were prevented by supplementation with glutathione monoethylester but not ascorbate. Tissue levels of inhibitory neurochemicals were unchanged. Depletion of glutathione appears to induce enlarged lymphoid aggregates by recruitment of lymphocytes from the peripheral circulation. A component of the inflammation that develops in
inflammatory bowel disease
could be related to depletion of tissue levels of glutathione.
...
PMID:Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model. 1121 24
Glycine protects mammalian intestine against oxidative damage caused by ischaemia-reperfusion (IR) injury and prevents or reverses experimentally-induced colitis. However the mechanism of protection remains largely unknown. The objectives of the current study were to demonstrate directly glycine-mediated protection of human intestinal epithelial cells and to determine the requirement for glycine uptake by the specific transporter GLYT1. Exogenous glycine protected human intestinal Caco-2 and HCT-8 cells against the oxidative agent tert-butylhydroperoxide and reduced the intracellular concentration of reactive oxygen species, when applied prior to but not concomitant with the oxidative challenge. Glycine given prior to oxidative challenge preserved intracellular glutathione concentration but had no effect on the rate of glycine uptake. Protection was dependent on GLYT1 activity, being blocked by a specific GLYT1 inhibitor, supporting a requirement for intracellular glycine accumulation. Maintained intracellular glutathione content is indicated as a mechanism through which the protective effect may in part be mediated. However expression of the genes encoding GLYT1 and the glutathione synthesising enzymes
glutamate-cysteine ligase
, both catalytic and modifier subunits, and glutathione synthetase was not altered by glycine or tert-butylhydroperoxide, suggesting transcriptional regulation is not involved. This work has demonstrated a novel role of GLYT1 in intestine and shown that intestinal epithelial cells respond directly to oxidative challenge without reliance on extra-epithelial tissues or functions such as neurone, blood-flow or immune responses for antioxidant defence. The protective actions of glycine and maintenance of epithelial antioxidant defences suggest it may be beneficial in treatment of
inflammatory bowel disease
.
...
PMID:Glycine transporter GLYT1 is essential for glycine-mediated protection of human intestinal epithelial cells against oxidative damage. 2036 26
The gastrointestinal tract is exposed to pro-oxidants from food, host immune factors, and microbial pathogens, which may induce oxidative damage. Oxidative stress has been shown to play an important role in the onset of
inflammatory bowel disease
. This study aimed to use a novel model to evaluate the effects of a screened natural component and explore its possible mechanism. An in vitro oxidative stress Caco2 cell model induced by H
2
O
2
was established using a real-time cellular analysis system and verified by addition of glutathione (GSH). A variety of plant components were chosen for the screening. Quercetin was the most effective phytochemical to alleviate the decreased cell index caused by H
2
O
2
among the tested plant components. Furthermore, quercetin ameliorated dextran sulfate sodium salt (DSS)-induced colitis and further increased the serum GSH. The mechanism of quercetin protection was explored in Caco2. Reversed H
2
O
2
-induced cell damage and decreased reactive oxygen species and apoptosis ratio were observed in quercetin-treated cells. Also, quercetin increased expression of the
glutamate-cysteine ligase
catalytic subunit (GCLC), the first rate-limiting enzyme of glutathione synthesis, and increased intracellular GSH concentration under H
2
O
2
treatment. This effect was abolished by the GCLC inhibitor buthionine sulfoximine. These results indicated that quercetin can improve cell proliferation and increase intracellular GSH concentrations by upregulating transcription of GCLC to eliminate excessive reactive oxygen species (ROS). Increased extracellular H
2
O
2
concentration induced by quercetin under oxidative stress was related to the inhibition of AQP3 and upregulation of NOX1/2, which may contribute to the observed protective effects of quercetin. Moreover, the novel H
2
O
2
-induced oxidative stress cell model based on the real-time cellular analysis system was an effective model to screen natural products to deal with intestinal oxidative damage and help accelerate the discovery of new drugs for
inflammatory bowel disease
(
IBD
).
...
PMID:Quercetin Alleviates Intestinal Oxidative Damage Induced by H
2
O
2
via Modulation of GSH: In Vitro Screening and In Vivo Evaluation in a Colitis Model of Mice. 3230 44
