Glutathione supplementation improves oxidative damage in experimental colitis

Loguercio, C.; D’Argenio, Giuseppe; Cave, M. Delle; Cosenza, V.; Valle, Nicola Della; Mazzacca, G; Blanco, C. Del Vecchio

doi:10.1016/s1590-8658(03)00379-7

Cited by 59 publications

(38 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We therefore propose that flavins and thiols act as redox mediators in the human gut and that electrons are finally transferred to oxygen (Figure 3b). Accordingly, F. prausnitzii rim formation in basal medium with riboflavin was also facilitated by glutathione, which is a primary thiolcontaining antioxidant in the gut (Loguercio, 2003;Burrin and Stoll, 2007). To measure the consumption of oxygen, cells were grown in a vial containing yeast extract, casitone, SCFAs including acetate and glucose (YCFAG) broth with oxygen in the gas phase.…”

Section: Resultsmentioning

confidence: 99%

The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases

et al. 2012

View full text Add to dashboard Cite

Faecalibacterium prausnitzii is one of the most abundant bacteria in the human gut ecosystem and it is an important supplier of butyrate to the colonic epithelium. Low numbers of faecalibacteria have been associated with inflammatory bowel disease. Despite being extremely oxygen sensitive, F. prausnitzii is found adherent to the gut mucosa where oxygen diffuses from epithelial cells. This paradox is now explained on the basis of gas tube experiments, flavin-dependent reduction of 5,5′-dithiobis-2-nitrobenzoate and microbial fuel cell experiments. The results show that F. prausnitzii employs an extracellular electron shuttle of flavins and thiols to transfer electrons to oxygen. Both compounds are present in the healthy human gut. Our observations may have important implications for the treatment of patients with Crohn's disease, for example, with flavin- or antioxidant rich diets, and they provide a novel key insight in host–microbe interactions at the gut barrier.

show abstract

Section: Resultsmentioning

confidence: 99%

The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases

et al. 2012

View full text Add to dashboard Cite

show abstract

“…13,37,38) Indeed, it has been reported that GSH supplementation improved oxidative damage in TNBS colitis. 39) Pretreatment with coumarin (5 mg/kg) and 4-hydroxycoumarin (5, 10, 25 mg/kg) in the acute phase of the inflammatory process induced by TNBS/ethanol, protected against colonic GSH depletion and restored the levels toward the normal value. This counteraction on colonic GSH depletion may be related to the action of these compounds as inhibitors of prostaglandin biosynthesis, 17) since one of the sources of production of free radicals is the oxidation of arachidonic acid either through the lipooxygenase or cyclooxygenase reactions.…”

Section: Discussionmentioning

confidence: 96%

“…A third possible source is the oxidation of arachidonic acid either through the lipooxygenase reaction, producing leukotrienes, or the prostaglandin generating cyclooxygenase reaction. 34) GSH plays a key role in controlling the redox state of the cell through several mechanisms, including scavenging of ROS and keeping the enzyme GSH peroxidase in a reduced state. 35) Decreased GSH levels, which are indicative of oxidant stress, have been detected in human 36) and experimental colitis.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Luchini

Rodrigues-Orsi

Cestari

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.

show abstract

“…A marked reduction of intestinal mucosa damage was also obtained in the TNBS model, both by supplementing the rats with a single dose of GSH before colitis induction (effect on disease onset) and by giving them repeated daily amounts of the tripeptide after colitis induction (effect on disease progression). In the first condition, GSH supplementation partly but significantly prevented lipid peroxidation and tissue damage; in the chronic model, daily GSH intraperitoneal injection completely restored the GSH loss and afforded good control of mucosal injury (158). In DSS-induced colitis in mice, gut mucosal levels of GSH were improved by NAC treatment, and histological damage of the colonic mucosa was partially prevented (294).…”

Section: Redox Imbalance In Ibdmentioning

confidence: 97%

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Biasi

Leonarduzzi

Oteiza

et al. 2013

Antioxidants & Redox Signaling

220

145

View full text Add to dashboard Cite

Oxidative stress is thought to play a key role in the development of intestinal damage in inflammatory bowel disease (IBD), because of its primary involvement in intestinal cells' aberrant immune and inflammatory responses to dietary antigens and to the commensal bacteria. During the active disease phase, activated leukocytes generate not only a wide spectrum of pro-inflammatory cytokines, but also excess oxidative reactions, which markedly alter the redox equilibrium within the gut mucosa, and maintain inflammation by inducing redoxsensitive signaling pathways and transcription factors. Moreover, several inflammatory molecules generate further oxidation products, leading to a self-sustaining and auto-amplifying vicious circle, which eventually impairs the gut barrier. The current treatment of IBD consists of long-term conventional anti-inflammatory therapy and often leads to drug refractoriness or intolerance, limiting patients' quality of life. Immune modulators or anti-tumor necrosis factor a antibodies have recently been used, but all carry the risk of significant side effects and a poor treatment response. Recent developments in molecular medicine point to the possibility of treating the oxidative stress associated with IBD, by designing a proper supplementation of specific lipids to induce local production of anti-inflammatory derivatives, as well as by developing biological therapies that target selective molecules (i.e., nuclear factor-jB, NADPH oxidase, prohibitins, or inflammasomes) involved in redox signaling. The clinical significance of oxidative stress in IBD is now becoming clear, and may soon lead to important new therapeutic options to lessen intestinal damage in this disease.

show abstract

Glutathione supplementation improves oxidative damage in experimental colitis

Cited by 59 publications

References 19 publications

The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases

The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Contact Info

Product

Resources

About