N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice

Amrouche-Mekkioui, I.; Djerdjouri, Bahia

doi:10.1016/j.ejphar.2012.06.014

Cited by 75 publications

(65 citation statements)

References 52 publications

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“…Administration of DSS in drinking water produces acute or chronic colitis, which leads to weight loss, diarrhea, rectal bleeding, and RONS production. 3,6,34,35 The keratin 8 (K8) knockout (K8 2/2 ) mouse develops an early Th2-type ulcerative colitis similar to humans, with epithelial hyperproliferation. 1,4,36-39 K8 2/2 mice display an alteration in ion transport, leading to chloride secretion caused by epithelial ion transporter mistargeting and mild diarrhea.…”

mentioning

confidence: 98%

In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

Asghar

Emani²,

Alam

et al. 2014

Inflammatory Bowel Diseases

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mentioning

confidence: 98%

In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

Asghar

Emani²,

Alam

et al. 2014

Inflammatory Bowel Diseases

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“…Within the damaged epithelium, neutrophils and macrophages are the most common immune cells present. Therapies that target the downstream mediators of these cells, such as reactive oxygen species, are therefore protective (Krieglstein et al 2001;Amrouche-Mekkioui and Djerdjouri 2012;Vong et al 2012;Yasukawa et al 2012). While the acute chemical-induced colitis models typically only incorporate features of innate biology (both epithelial and immune), the chronic and progressive models typically illustrate a complex interplay between innate biology and adaptive immune responses.…”

Section: Considerations For Choosing a Preclinical Modelmentioning

confidence: 99%

Murine Models of Inflammatory Bowel Disease (IBD)

DeVoss¹,

Diehl²

2013

Toxicol Pathol

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Animal models of human disease are a critical tool in both basic research and drug development. The results of preclinical efficacy studies often inform progression of therapeutic candidates through the drug development pipeline; however, the extent to which results in inflammatory bowel disease (IBD) models predict human drug response is an ongoing concern. This review discusses how murine models are currently being used in IBD research. We focus on the considerations and caveats for commonly used models in preclinical efficacy studies and discuss the value of models that utilize specific pathogenic pathways of interest rather than model all aspects of human disease.

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“…Recent reports demonstrated that NF-κB may regulate iNOS expression and NO production [49]–[51]. NAC has been shown to modulate inflammatory responses through signaling pathways that control pro-inflammatory NF-κB activation [29], [52]. Since the results of this study show significantly increased iNOS protein and mRNA expression following TCE exposure, it was, therefore, of interest to analyze NF-κB activation.…”

Section: Resultsmentioning

confidence: 69%

“…Interestingly, NAC supplementation not only ameliorated the TCE-induced nitrosative stress, GSH and NF-κB p65 activation, but also the markers of autoimmune response, as evident from decreased levels of autoantibodies in the sera. NAC treatment can reduce the formation of ONOO - possibly by a simultaneous inhibition of ROS and NO via the suppression of NF-κB-mediated induction of iNOS expression [29], [33], [53]. Based on these findings, we conclude that TCE exposure activated iNOS and generated free radicals (RONS) leading to increased ONOO - , which led to increased formation of modified proteins (NT or nitrated proteins) which can act as immunogen or neoantigens.…”

Section: Discussionmentioning

confidence: 70%

“…These immunogen/neoantigens might activate lymphocytes or cause break in immune tolerance, leading to autoimmune response [6]-[8], [21]. NAC supplementation could ameliorate TCE-induced autoimmunity potentially via suppressing/averting NF-κB and iNOS activity or by directly scavenging free radicals (O 2 .- , NO and ONOO - ) leading to reduction in neoantigen formation and thus, an autoimmune response [29], [32], [33], [54], [55]. Fig.…”

Section: Discussionmentioning

confidence: 99%

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Nitrosative Stress and Nitrated Proteins in Trichloroethene-Mediated Autoimmunity

Wang

Luo

et al. 2014

PLoS ONE

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Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC) supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼250 mg/kg/day via drinking water). TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT) in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.

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N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice

Cited by 75 publications

References 52 publications

In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

Murine Models of Inflammatory Bowel Disease (IBD)

Nitrosative Stress and Nitrated Proteins in Trichloroethene-Mediated Autoimmunity

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