Protective action of NADPH oxidase inhibitors and role of NADPH oxidase in pathogenesis of colon inflammation in mice

Ramonaitė, Rima; Skiecevičienė, Jurgita; Juzėnas, Simonas; Šaltenienė, Violeta; Kupčinskas, Juozas; Matusevičius, Paulius; Borutaitė, Vilmantė; Kupčinskas, Limas

doi:10.3748/wjg.v20.i35.12533

Cited by 21 publications

(17 citation statements)

References 36 publications

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“…Specifically, the expression of NOX1 was upregulated in the inflamed colon during dextran sulfate sodium (DSS)-and tumor necrosis factor (TNF)-a-induced colitis. Inhibition of ROS production by apocynin, an antioxidant and a nonselective NOX inhibitor in leukocytes (Heumuller et al, 2008), reduced the severity of colonic inflammation (Mouzaoui et al, 2014;Ramonaite et al, 2014). We also reported that NOX1-deficient mice exhibited resistance to intestinal mucositis induced by an anticancer agent, 5-fluorouracil (Yasuda et al, 2012).…”

Section: Introductionmentioning

confidence: 66%

“…Apocynin, an antioxidant and inhibitor of phagocytic NADPH oxidase, decreased colonic inflammation in DSS-and TNF-a-induced experimental murine colitis models (Mouzaoui et al, 2014;Ramonaite et al, 2014). Because the main source of ROS during colitis has been considered to be macrophages and neutrophils recruited into the inflamed colonic mucosa, the phagocytic isoform NOX2, rather than the nonphagocytic/ colonic isoform NOX1, appears to play an important role in the pathogenesis of IBD (Grisham and Granger, 1988;Maloy and Powrie, 2011).…”

Section: Discussionmentioning

confidence: 99%

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NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid–Induced Murine Colitis

Yokota

Tsuzuki

Shimada

et al. 2016

J Pharmacol Exp Ther

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NOX1/NADPH oxidase, a nonphagocytic isoform of reactive oxygen species-producing enzymes, is highly expressed in the colon, but the physiologic and pathophysiologic roles of this isoform are not fully understood. The present study investigated the role of NOX1 in the development of colonic inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. Intrarectal injection of TNBS caused severe colitis accompanied by body weight loss, diarrhea, and increased myeloperoxidase (MPO) activity in wild-type (WT) mice. In contrast, the severity of colitis was significantly attenuated in NOX1-deficient (NOX1KO) mice (the inhibitions of macroscopic damage score, body weight loss, diarrhea score, and MPO activity were 73.1%, 36.8%, 83.3%, and 98.4%, respectively). TNBS-induced upregulation of inflammatory cytokines (tumor necrosis factor (TNF)-a and interleukin (IL)-1b), chemokines (CXCL1 and CXLC2), and inducible nitric oxide synthase (iNOS) was also significantly less in NOX1KO than in WT mice (the inhibitions were 100.8%, 89.0%, 63.5%, 96.7%, and 97.1%, respectively). Expression of NOX1 mRNA was detected not only in the lamina propria but also in peritoneal macrophages isolated from WT mice. Increased expression of TNF-a, IL-1b, and iNOS in peritoneal macrophages exposed to lipopolysaccharide was significantly attenuated in macrophages isolated from NOX1KO mice (68.1%, 67.0%, and 79.3% inhibition, respectively). These findings suggest that NOX1/NADPH oxidase plays an important role in the pathogenesis of TNBS-induced colonic inflammation via upregulation of inflammatory cytokines, chemokines, and iNOS. NOX1 in colonic macrophages may become a potential target in pharmacologic intervention for inflammatory bowel disease.

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Section: Introductionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid–Induced Murine Colitis

Yokota

Tsuzuki

Shimada

et al. 2016

J Pharmacol Exp Ther

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“…BALB/c mice used in this study come from our previous research that aimed to evaluate the role of NADPH oxidase in pathogenesis of colon inflammation [ 17 ]. Acute and chronic colon inflammation in the animals was induced by oral administration of 3.5 % dextran sulphate sodium (DSS, TdB Consultancy, Uppsala, Sweden).…”

Section: Methodsmentioning

confidence: 99%

“…Acute and chronic colon inflammation in the animals was induced by oral administration of 3.5 % dextran sulphate sodium (DSS, TdB Consultancy, Uppsala, Sweden). Detailed methods of experimental colitis induction in mice and clinical data analysis have been published in R. Ramonaite et al paper [ 17 ] and our current study included only histological samples of the colon. Lithuanian Animal Ethics Committee approved the design of experiments (Protocol no.…”

Section: Methodsmentioning

confidence: 99%

Digital imaging of colon tissue: method for evaluation of inflammation severity by spatial frequency features of the histological images

et al. 2015

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Background The efficacy of histological analysis of colon sections used for evaluation of inflammation severity can be improved by means of digital imaging giving quantitative estimates of main diagnostic features. The aim of this study was to reveal most valuable diagnostic features reflecting inflammation severity in colon and elaborate the evaluation method for computer-aided diagnostics. Methods Tissue specimens from 24 BALB/c mice and 15 patients were included in the study. Chronic and acute colon inflammation in mice was induced by oral administration of dextran sulphate sodium (DSS) solution, while mice in the control group did not get DSS. Human samples of inflamed colon tissue were obtained from patients with ulcerative colitis ( n = 6). Non-inflamed colon tissue of control subjects ( n = 9) was obtained from patients with irritable bowel syndrome or functional obstipation. Analysis of morphological changes in mice and human colon mucosa was performed using 4-μm haematoxylin-eosin (HE) sections. The features reflecting morphological changes in the images of colon mucosa were calculated by convolution of Gabor filter bank and array of pixel values. All features were generalized by calculating mean, histogram skewness and entropy of every image response. Principal component analysis was used to construct optimal representation of morphological changes. Results First principal component (PC1) was representing the major part of features variation (97 % in mice and 71 % in human specimens) and was selected as a measure of inflammation severity. Validation of new measure was performed by means of custom-made software realizing double blind comparison of differences in PC1 with expert’s opinion about inflammation severity presented in two compared pictures. Overall accuracy of 80 % for mice and 67 % for human was reached. Conclusion Principal component analysis of spatial frequency features of histological images may provide continuous scale estimation of inflammation severity of colon tissue.

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“…A number of studies have shown the potential of apocynin as a possible antiinflammatory drug in various inflammatory conditions such as airway inflammation [Kim et al, 2010a[Kim et al, , 2012a, arthritis [Impellizzeri et al, 2011;Kim et al, 2012a], and experimental Crohn's disease [Rachmilewitz et al, 1997]. Apocynin also has protective properties in a dextran sulfate sodium (DSS)-induced ulcerative colitis model [Marin et al, 2013;Ramonaite et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

Apocynin Suppresses Lipopolysaccharide‐Induced Inflammatory Responses Through the Inhibition of MAP Kinase Signaling Pathway in RAW264.7 Cells

Hwang

Lee

Park

et al. 2016

Drug Development Research

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Apocynin, an inhibitor of NADPH oxidase, exhibits anti-inflammatory properties in ulcerative colitis. However, the underlying mechanism by which apocynin exerts this effect has not been clearly demonstrated. The objective of this study was to elucidate the anti-inflammatory mechanism of apocynin in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. Apocynin inhibited LPS-induced extracellular secretion of the pro-inflammatory mediators, nitric oxide (NO) and PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2. Apocynin also suppressed LPS-induced secretion of the pro-inflammatory cytokine, tumor necrosis factor-α and LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. To elucidate the underlying anti-inflammatory mechanism of apocynin, the involvement of the mitogen-activated protein (MAP) kinases, c-jun N-terminal kinase, extracellular signal-regulated kinases, and p38 was examined. Apocynin attenuated LPS-induced activation of all three MAP kinases in a concentration-dependent manner. The present study demonstrates apocynin exerts anti-inflammatory activity via the suppression of MAP kinase signaling pathways in LPS-challenged RAW264.7 macrophage cells. Drug Dev Res, 2016. © 2016 Wiley Periodicals, Inc.

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Protective action of NADPH oxidase inhibitors and role of NADPH oxidase in pathogenesis of colon inflammation in mice

Abstract: Our study revealed the importance of NADPH oxidase in the pathogenesis of both acute and chronic inflammation of the colon.

Cited by 21 publications

References 36 publications

NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid–Induced Murine Colitis

NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid–Induced Murine Colitis

Digital imaging of colon tissue: method for evaluation of inflammation severity by spatial frequency features of the histological images

Apocynin Suppresses Lipopolysaccharide‐Induced Inflammatory Responses Through the Inhibition of MAP Kinase Signaling Pathway in RAW264.7 Cells

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