The Role of Glutathione in Intestinal Dysfunction

Jefferies, Heather; Bot, Joan; Coster, Jane; Khalil, Alizan Abdul; Hall, John C.; Mccauley, Rosalie

doi:10.1080/08941930390250214

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…Glutamate is an important precursor and intermediate in the synthesis and metabolic recycling of other amino acids, and with the urea cycle, in the gut [ 38 , 39 , 47 , 48 ]. Amino acids closely interlinked with glutamate metabolism include arginine, which also contributes to epithelium restitution, preserves barrier function, prevents accumulation of ammonia in the gut, and attenuates intestinal tissue damage [ 49 – 51 ], and glutathione, which protects the epithelium from damage by oxidative stress [ 52 , 53 ]. Altogether, major functions of glutamate in the gut appear to be its role as a key intermediate in gut amino acid metabolism and nitrogen cycling, maintenance of epithelial integrity, and preservation of barrier function.…”

Section: Resultsmentioning

confidence: 99%

Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota

et al. 2015

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BackgroundChronic malnutrition, termed stunting, is defined as suboptimal linear growth, affects one third of children in developing countries, and leads to increased mortality and poor developmental outcomes. The causes of childhood stunting are unknown, and strategies to improve growth and related outcomes in children have only had modest impacts. Recent studies have shown that the ecosystem of microbes in the human gut, termed the microbiota, can induce changes in weight. However, the specific changes in the gut microbiota that contribute to growth remain unknown, and no studies have investigated the gut microbiota as a determinant of chronic malnutrition.ResultsWe performed secondary analyses of data from two well-characterized twin cohorts of children from Malawi and Bangladesh to identify bacterial genera associated with linear growth. In a case-control analysis, we used the graphical lasso to estimate covariance network models of gut microbial interactions from relative genus abundances and used network analysis methods to select genera associated with stunting severity. In longitudinal analyses, we determined associations between these selected microbes and linear growth using between-within twin regression models to adjust for confounding and introduce temporality. Reduced microbiota diversity and increased covariance network density were associated with stunting severity, while increased relative abundance of Acidaminococcus sp. was associated with future linear growth deficits.ConclusionsWe show that length growth in children is associated with community-wide changes in the gut microbiota and with the abundance of the bacterial genus, Acidaminococcus. Larger cohorts are needed to confirm these findings and to clarify the mechanisms involved.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0089-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota

et al. 2015

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“…The epithelial cells of the gut are highly dependent on GSH, the deficiency of which leads to a marked cellular degeneration, suggesting that enhanced GSH might be of therapeutic value in protecting the gastrointestinal epithelia against toxicity associated with oxidative damage such as seen with chemotherapy and radiation (9,10,11). For example, adriamycin and methotrexate, commonly used in breast cancer treatment, promote free radical formation and decrease GSH in various organs (12,13).…”

Section: Introductionmentioning

confidence: 99%

Glutamine Affects Glutathione Recycling Enzymes in a DMBA-Induced Breast Cancer Model

Kaufmann

Тодорова

Luo

et al. 2008

Nutrition and Cancer

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Malignancy depletes host glutathione (GSH) levels to increase treatment-related toxicity and increases itself to resist the treatments. Our previous studies have shown that dietary glutamine (GLN) prevented 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors through enhancing gut GSH release and reducing tumor GSH level. In addition, GSH synthesis, metabolism, and recycling are accomplished in gamma-glutamyl cycle. We hypothesized that the GLN prevention might be through a differential regulation of the gamma-glutamyl cycle enzymes. Female Sprague-Dawley rats were randomized into DMBA-tumor bearing, DMBA-treated, and control groups subdivided into GLN and water groups. GLN supplementation was given at 1 g/kg/day by gastric gavage. The activities and messenger RNA levels of gamma-glutamyl transpeptidase (GTP), gamma-glutamylcysteine synthetase (GCS), 5-oxo-L-prolinase (OPase), gamma-glutamyl transferase (GTF), and glutaminase (GLNase) were determined in gut mucosa and breast tumor using specific enzyme assays and semiquantitative reverse transcription polymerase chain reaction. GLN upregulated gut GTP, GCS, OPase, and GLNase in DMBA-tumor bearing, DMBA-treated, and/or control rats; however, it downregulated these enzymes in the tumor. The paradoxical effect of GLN on key GSH recycling enzymes in the gut versus tumor suggests that dietary supplemental GLN could be used in the clinical practice to increase the therapeutic index of cancer treatments by protecting normal tissues from, and sensitizing tumor cells to, chemotherapy and radiation-related injury.

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“…SAME is a precursor of glutathione, an antioxidant. Glutathione is a powerful cytoprotectant in the intestine, and glutathione supplementation has been proposed as a promising therapy for I/R injury [16]. In this study, SAME reduced intestinal I/R injury, the associated transaminase elevations, lipid peroxidation, and increased serum TAC.…”

Section: Discussionmentioning

confidence: 65%

Comparative Effects of Triflusal, S-Adenosylmethionine, and Dextromethorphan over Intestinal Ischemia/Reperfusion Injury

Cámara-Lemarroy

Garza

Cordero-Pérez

et al. 2011

The Scientific World JOURNAL

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Ischemia/reperfusion (I/R) is a condition that stimulates an intense inflammatory response. No ideal treatment exists. Triflusal is an antiplatelet salicylate derivative with anti-inflammatory effects. S-adenosylmethionine is a metabolic precursor for glutathione, an endogenous antioxidant. Dextromethorphan is a low-affinity N-methyl-D-aspartate receptor inhibitor. There is evidence that these agents modulate some of the pathways involved in I/R physiopathology. Intestinal I/R was induced in rats by clamping the superior mesenteric artery for 60 minutes, followed by 60 minutes of reperfusion. Rats either received saline or the drugs studied. At the end of the procedure, serum concentrations of tumor necrosis factor-alpha (TNF-alpha), malonaldehyde (MDA), and total antioxidant capacity (TAC) were determined and intestinal morphology analyzed. I/R resulted in tissue damage, serum TNF-alpha and MDA elevations, and depletion of TAC. All drugs showed tissue protection. Only triflusal reduced TNF-alpha levels. All drugs lowered MDA levels, but only triflusal and S-adenosylmethionine maintained the serum TAC.

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The Role of Glutathione in Intestinal Dysfunction

Cited by 12 publications

References 47 publications

Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota

Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota

Glutamine Affects Glutathione Recycling Enzymes in a DMBA-Induced Breast Cancer Model

Comparative Effects of Triflusal, S-Adenosylmethionine, and Dextromethorphan over Intestinal Ischemia/Reperfusion Injury

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