Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel disease

Hatoum, Ossama A.; Binion, David G.; Gutterman, David D.

doi:10.1111/j.1365-2362.2005.01567.x

Cited by 46 publications

(43 citation statements)

References 153 publications

(192 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40) It has been reported that HIF-1α is overexpressed in colitis affected human and murine colon tissues. 13,41) In agreement with previous observations, HIF-1α was found to be elevated in the DSS group, but CA was found to reduce this increase, not to the same extent as SFZ. These results indicate that the inflammation observed in our DSS model is the result of both COX-2 and HIF-1α mediated response and that the inhibition of inflammatory response by CA is effective against both inflammatory molecules.…”

Section: Discussionsupporting

confidence: 81%

The Therapeutic Effect of Chelidonic Acid on Ulcerative Colitis

Kim

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Chelidonic acid (CA), a constituent of Chelidonium majus L., has many pharmacological effects, including mild analgesic and antimicrobial effects. However, the effects of CA on intestinal inflammation and the molecular mechanisms responsible are poorly understood. The aim of this study was to investigate the protective effects of CA against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Mice treated with DSS displayed obvious clinic signs, such as, body weight loss and a shortening of colon length, but the administration of CA attenuated both of these signs. Additionally, CA was found to regulate levels of interleukin-6 and tumor necrosis factor-α in serum. In colonic tissues,

show abstract

Section: Discussionsupporting

confidence: 81%

The Therapeutic Effect of Chelidonic Acid on Ulcerative Colitis

Kim

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…A number of studies have implicated the occurrence of hypoxia in mucosal inflammatory diseases such as IBD [12]. Surgical specimens from patients with IBD have revealed prominent hypoxia-inducible factor (HIF)-1 and HIF-2 activation associated with increased vascular density in diseased areas [13].…”

Section: Hypoxia and Mucosal Inflammationmentioning

confidence: 99%

“…Surgical specimens from patients with IBD have revealed prominent hypoxia-inducible factor (HIF)-1 and HIF-2 activation associated with increased vascular density in diseased areas [13]. Other studies in humans have revealed that a number of microvascular abnormalities may contribute to diminished blood flow to the intestine in IBD, including the loss of endothelial nitric oxide generation and enhanced tissue vasoconstrictor production [12]. Moreover, Vascular endothelial growth factor-dependent angiogenesis appears to be an integral part of human IBD [14].…”

Section: Hypoxia and Mucosal Inflammationmentioning

confidence: 99%

Hypoxia and gastrointestinal disease

2007

View full text Add to dashboard Cite

The gastrointestinal mucosa is a richly perfused vascular bed directly juxtaposed with the anaerobic and nonsterile lumen of the gut. As such, intestinal epithelial cells, which line the mucosa, experience a uniquely steep physiologic oxygen gradient in comparison with other cells of the body. Inflammation associated with a loss of epithelial barrier function and unregulated exposure of the mucosal immune system to luminal antigens leads to inflammatory bowel disease (IBD), a relatively common disorder with severe morbidity and a limited therapeutic repertoire. During IBD, increased tissue metabolism and vasculitis renders the chronically inflamed mucosa and particularly the epithelium hypoxic, giving rise to the activation of the hypoxia-responsive transcription factor hypoxia-inducible factor (HIF). Recent studies utilizing conditional intestinal epithelial hif1a-null mice have revealed a protective role for epithelial HIF-1α in murine models of IBD. Such protection occurs, at least in part, through HIF-dependent induction of barrier-protective genes in the epithelium. More recently, studies employing pharmacologic activation of HIF via inhibition of HIF prolyl hydroxylases revealed a profoundly protective effect of these agents in murine models of colitis. In this paper, we review this pathway in detail and examine the therapeutic potential for targeting HIF hydroxylases in intestinal mucosal inflammatory disease.

show abstract

“…A number of clinical and experimental studies showed oxygen deprivation of colonic epithelial cells in inflammatory bowel disease (IBD). 5,10,25,36 Moreover, prevention of hypoxia by heparin 37 or endothelin-1 receptor antagonist 38 significantly reduced the degree of mucosal injury and inflammatory response. In addition to endothelial damage and intravascular congestion, our present study demonstrated hypoxia in colonic surface epithelial cells that preceded the enhanced colonic EP.…”

Section: Endothelial Damage In Ulcerative Colitismentioning

confidence: 99%

Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

Tolstanova

Deng

French

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

The role of endothelial damage and increased vascular permeability (VP) in the pathogenesis of ulcerative colitis (UC) has not been investigated. We examined using functional, morphologic, and molecular biologic studies whether and to what extent the endothelial barrier dysfunction precedes enhanced epithelial permeability (EP) and the development of mucosal lesions during the early stages of experimental UC. We showed that in rats with iodoacetamide (IA)-induced UC increased colonic VP occurs early (ie, 2.6-fold increase at 15 min, Po0.01) preceding changes in epithelial barrier permeability. EP was unchanged at 15 and 30 min after IA administration and was increased 1.9-fold at 1 h and 6.7-fold at 2 h (both Po0.001) after IA. In the dextran sodium sulfate-induced slowly developing UC, colonic VP was significantly increased in 2 days (Po0.05) and EP only in 4 days (Po0.05). Mucosal endothelial injury led to hypoxia (Po0.05) of colonic surface epithelial cells 30 min after IA administration that was associated with increased expressions of transcription factors hypoxia-inducible factor-1a and early growth response-1. Electron and light microscopy demonstrated areas of colonic mucosa with perivascular edema covered by intact layer of surface epithelial cells in both rat and mouse models of UC. This is the first demonstration in four models of UC that endothelial damage, increased colonic VP, perivascular edema, and epithelial hypoxia precede epithelial barrier dysfunction that is followed by erosions, ulceration, and inflammation in UC. KEYWORDS: endothelial damage; epithelial permeability; hypoxia; inflammatory bowel disease; ulcerative colitis; vascular permeability Ulcerative colitis (UC) is characterized by chronic, recurrent ulcers and inflammation of the colonic mucosa. It has been postulated that impaired epithelial barrier function, resulting in penetration of bacteria and other antigens into the mucosa, is one of the major factors of UC pathogenesis.

show abstract

Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel disease

Cited by 46 publications

References 153 publications

The Therapeutic Effect of Chelidonic Acid on Ulcerative Colitis

The Therapeutic Effect of Chelidonic Acid on Ulcerative Colitis

Hypoxia and gastrointestinal disease

Early endothelial damage and increased colonic vascular permeability in the development of experimental ulcerative colitis in rats and mice

Contact Info

Product

Resources

About