Biomarkers for Assessing Mucosal Barrier Dysfunction Induced by Chemotherapy: Identifying a Rapid and Simple Biomarker

Kong, Wencheng; Wang, Jian; Ping, Xiaochun; Shen, Jing Nan; Ni, Xiaoqing; Liu, Fangnan; Bao-jun, YU; Li, Yousheng

doi:10.7754/clin.lab.2014.140712

Cited by 9 publications

(9 citation statements)

References 28 publications

(67 reference statements)

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“…Thus, increased DAO levels represent increased gut permeability. DAO has been used as a biomarker for intestinal barrier dysfunction in various diseases and has been cross validated with other markers of gut permeability 37 38 39 40 41 42 43 .…”

Section: Discussionmentioning

confidence: 99%

Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease

Lemesch

Ribitsch

Schilcher

et al. 2016

Sci Rep

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Bacterial infection and sepsis are common complications of chronic kidney disease (CKD). A vicious cycle of increased gut permeability, endotoxemia, inadequate activation of the innate immune system and resulting innate immune dysfunction is hypothesized. We assessed endotoxemia, neutrophil function and its relation to oxidative stress, inflammation and gut permeability in patients with CKD grade 3–5 without renal replacement therapy (CKD group, n = 57), patients with CKD stage 5 undergoing haemodialysis (HD, n = 32) or peritoneal dialysis (PD, n = 28) and patients after kidney transplantation (KT, n = 67) in a cross-sectional observational study. In HD patients, endotoxin serum levels were elevated and neutrophil phagocytic capacity was decreased compared to all other groups. Patients on HD had a significantly higher mortality, due to infections during follow up, compared to PD (p = 0.022). Oxidative stress, neutrophil energy charge, systemic inflammation and gut permeability could not completely explain these differences. Our findings suggest that dialysis modality and not renal function per se determine the development of neutrophil dysfunction and endotoxemia in CKD-patients. HD patients are particularly prone to neutrophil dysfunction and endotoxemia whereas neutrophil function seems to improve after KT. Multi-target approaches are therefore warranted to improve neutrophil function and potentially reduce the rate of infections with patients undergoing haemodialysis.

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Section: Discussionmentioning

confidence: 99%

Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease

Lemesch

Ribitsch

Schilcher

et al. 2016

Sci Rep

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“…The increase in small intestinal permeability is likely to represent in part the effect of the circulating inflammatory mediators, such as IL-1β, TNF-α, IFN-γ, and lipopolysaccharide, which cause an increase in intestinal permeability. As intestinal permeability markers are hydrophilic and do not permeate across the bilipid enterocyte plasma membrane, changes in intestinal permeability are reflective of relative “tightness” or “leakiness” of the intestinal TJ barrier or the paracellular pathways ( 68 , 69 ). The abnormal increase in intestinal permeability in inflammatory diseases of the gut may be due to the intrinsic structural defect of the TJ barrier related to the underlying disease state or secondary to the effects of inflammatory process or inflammatory mediators, including IL-1β and TNF-α ( 7 , 26 , 46 , 58 , 68 , 70 , 71 ).…”

Section: Il-1β and Its Receptorsmentioning

confidence: 99%

“…As intestinal permeability markers are hydrophilic and do not permeate across the bilipid enterocyte plasma membrane, changes in intestinal permeability are reflective of relative “tightness” or “leakiness” of the intestinal TJ barrier or the paracellular pathways ( 68 , 69 ). The abnormal increase in intestinal permeability in inflammatory diseases of the gut may be due to the intrinsic structural defect of the TJ barrier related to the underlying disease state or secondary to the effects of inflammatory process or inflammatory mediators, including IL-1β and TNF-α ( 7 , 26 , 46 , 58 , 68 , 70 , 71 ). IL-1β at physiologically and clinically relevant concentrations, as seen in IBD and NEC, has been shown to cause an increase in intestinal epithelial TJ permeability ( 33 , 34 , 38 , 72 – 74 ).…”

Section: Il-1β and Its Receptorsmentioning

confidence: 99%

IL-1β and the Intestinal Epithelial Tight Junction Barrier

2021

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The intestinal epithelial tight junction (TJ) barrier controls the paracellular permeation of contents from the intestinal lumen into the intestinal tissue and systemic circulation. A defective intestinal TJ barrier has been implicated as an important pathogenic factor in inflammatory diseases of the gut including Crohn’s disease, ulcerative colitis, necrotizing enterocolitis, and celiac disease. Previous studies have shown that pro-inflammatory cytokines, which are produced during intestinal inflammation, including interleukin-1β (IL-1β), tumor necrosis factor-α, and interferon-γ, have important intestinal TJ barrier-modulating actions. Recent studies have shown that the IL-1β-induced increase in intestinal TJ permeability is an important contributing factor of intestinal inflammation. The IL-1β-induced increase in intestinal TJ permeability is mediated by regulatory signaling pathways and activation of nuclear transcription factor nuclear factor-κB, myosin light chain kinase gene activation, and post-transcriptional occludin gene modulation by microRNA and contributes to the intestinal inflammatory process. In this review, the regulatory role of IL-1β on intestinal TJ barrier, the intracellular mechanisms that mediate the IL-1β modulation of intestinal TJ permeability, and the potential therapeutic targeting of the TJ barrier are discussed.

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“…Many biomarkers have been considered for assessment of intestinal mucosal injury, but no standard approach for the use of such markers has yet been established. Previous studies have shown that sequential monitoring of DAO and citrulline levels is useful for evaluating intestinal mucosal injury in inflammatory bowel disease, ischemic intestinal disease, and cytotoxic chemotherapy 18,19 . Most of these studies showed that the degree of reduction in the levels of these substances reflects the severity of intestinal mucosal damage.…”

Section: Discussionmentioning

confidence: 99%

Monitoring of citrulline and diamine oxidase levels as biomarkers for intestinal mucositis during early-phase hematopoietic cell transplantation

2018

BCT

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Background： Gastrointestinal tract mucositis is a common side effect in the early phase of hematopoietic cell transplantation (HCT) , although reliable biomarkers have not yet been established. Since blood levels of citrulline and diamine oxidase(DAO)have been reported as specific markers of intestinal mucosal injury during cytotoxic cancer chemotherapy, we aimed to evaluate the relationship between circulating citrulline／DAO levels and the severity of gastrointestinal mucosal injury in patients with hematologic diseases who had undergone various types of HCT. Methods： Forty patients who received autologous(n＝21)and allogeneic HCT(n＝19； cord blood(n＝16) , peripheral blood(n＝3) )were enrolled in the study. Serial monitoring of plasma citrulline and serum DAO levels was prospectively performed from the day prior to the start of the conditioning regimen until day 28 post-HCT. Results： Citrulline and DAO levels significantly decreased after the start of conditioning. The recovery of citrulline and DAO levels tended to be delayed in cord blood transplant recipients, compared with autologous and allogeneic peripheral blood transplant groups, probably reflecting the severity of mucosal injury during the prolonged neutropenic period. The nadir levels for both markers were inversely associated with peak C-reactive protein levels. Discussion： There was a slight difference in the time-dependent courses of these biomarker levels between each type of HCT. The change of DAO levels was more parallel to the clinical parameters. Serially monitored citrulline and DAO levels may be promising biomarkers for assessing intestinal mucosal injury in the early phase of various types of HCT, although prospective studies including larger number of patients are warranted to confirm our observations.

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Biomarkers for Assessing Mucosal Barrier Dysfunction Induced by Chemotherapy: Identifying a Rapid and Simple Biomarker

Cited by 9 publications

References 28 publications

Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease

Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease

IL-1β and the Intestinal Epithelial Tight Junction Barrier

Monitoring of citrulline and diamine oxidase levels as biomarkers for intestinal mucositis during early-phase hematopoietic cell transplantation

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