Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide

Pravda, Jay

doi:10.3748/wjg.v28.i31.4263

Cited by 6 publications

(3 citation statements)

References 275 publications

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“…Previous studies showed that oxidative stress increases during the inflammatory response of UC ( 46 ). Even though, the intestine counts with antioxidants and molecules that have protective roles to counteract inflammation, a reduced expression of these agents could contribute to the enhanced inflammatory UCLD ( 47 ).…”

Section: Resultsmentioning

confidence: 98%

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring

Rivera,

Opazo,

Hernández-Armengol

et al. 2024

Front. Endocrinol.

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IntroductionGestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring).MethodsGestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10–E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment.ResultsThe HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring.DiscussionGestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.

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Section: Resultsmentioning

confidence: 98%

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring

Rivera,

Opazo,

Hernández-Armengol

et al. 2024

Front. Endocrinol.

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“…The two models of IBD here reported are based on the known role of LPS and H 2 O 2 in these intestinal disorders, CD and UC, respectively. Indeed, CD is often associated with increased levels of LPS in the serum of suffering patients [ 28 ], while in UC, a causal role of H 2 O 2 has been identified in both the pathogenesis and relapse of this IBD, and it is also a novel therapeutic target [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Toll-like Receptors and Cytokine Modulation by Goat Milk Extracellular Vesicles in a Model of Intestinal Inflammation

Ciucis

Fruscione

Paolis

et al. 2023

IJMS

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Extracellular vesicles (EVs) are nanometric spherical structures, enclosed in a lipid bilayer membrane and secreted by multiple cell types under specific physiologic and pathologic conditions. Their complex cargo modulates immune cells within an inflammatory microenvironment. Milk is one of the most promising sources of EVs in terms of massive recovery, and milk extracellular vesicles (mEVs) have immunomodulatory and anti-inflammatory effects. The aim of this study was to characterize goat mEVs’ immunomodulating activities on Toll-like receptors (TLRs) and related immune genes, including cytokines, using a porcine intestinal epithelial cell line (IPEC-J2) after the establishment of a pro-inflammatory environment. IPEC-J2 was exposed for 2 h to pro-inflammatory stimuli as a model of inflammatory bowel disease (IBD), namely LPS for Crohn’s disease (CD) and H2O2 for ulcerative colitis (UC); then, cells were treated with goat mEVs for 48 h. RT-qPCR and ELISA data showed that cell exposure to LPS or H2O2 caused a pro-inflammatory response, with increased gene expression of CXCL8, TNFA, NOS2 and the release of pro-inflammatory cytokines. In the LPS model, the treatment with mEVs after LPS determined the down-regulation of NOS2, MMP9, TLR5, TGFB1, IFNB, IL18 and IL12A gene expressions, as well as lower release of IL-18 in culture supernatants. At the same time, we observed the increased expression of TLR1, TLR2, TLR8 and EBI3. On the contrary, the treatment with mEVs after H2O2 exposure, the model of UC, determined the increased expression of MMP9 alongside the decrease in TGFB1, TLR8 and DEFB1, with a lower release of IL-1Ra in culture supernatants. Overall, our data showed that a 48 h treatment with mEVs after a pro-inflammatory stimulus significantly modulated the expression of several TLRs and cytokines in swine intestinal cells, in association with a decreased inflammation. These results further highlight the immunomodulatory potential of these nanosized structures and suggest their potential application in vivo.

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“…Increased oxidative damage is also associated with the metastatic phenotype in CRCs [12]. The intestinal peroxide radicals are also contributors to inducing ulcerative colitis by driving inflammatory events in the colon [13]. The inflammatory cascades are also associated with the promotion of various cancers including colorectal cancer [14,15].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Bis-Chalcones and Evaluation of Its Effect on Peroxide-Induced Cell Death and Lipopolysaccharide-Induced Cytokine Production

Tom,

Jacob,

Mathews

et al. 2023

Molecules

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Plant secondary metabolites are important sources of biologically active compounds with wide pharmacological potentials. Among the different classes, the chalcones form integral pharmacologically active agents. Natural chalcones and bis-chalcones exhibit high antioxidant and anti-inflammatory properties in various experiments. Studies are also underway to explore more biologically active bis-chalcones by chemical synthesis of these compounds. In this study, the effects of six synthetic bis-chalcones were evaluated in intestinal epithelial cells (IEC-6); further, the anti-inflammatory potentials were studied in lipopolysaccharide-induced cytokine production in macrophages. The synthesized bis-chalcones differ from each other first of all by the nature of the aromatic cores (functional group substitution, and their position) and by the size of a central alicycle. The exposure of IEC-6 cells to peroxide radicals reduced the cell viability; however, pre-treatment with the bis-chalcones improved the cell viability in these cells. The mechanism of action was observed to be the increased levels of glutathione and antioxidant enzyme activities. Further, these bis-chalcones also inhibited the LPS-stimulation-induced inflammatory cytokine production in RAW 264.7 macrophages. Overall, the present study indicated the cytoprotective and anti-inflammatory abilities of synthetic bis-chalcones.

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Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide

Cited by 6 publications

References 275 publications

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring

Toll-like Receptors and Cytokine Modulation by Goat Milk Extracellular Vesicles in a Model of Intestinal Inflammation

Synthesis of Bis-Chalcones and Evaluation of Its Effect on Peroxide-Induced Cell Death and Lipopolysaccharide-Induced Cytokine Production

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