A comparative analysis of two models of colitis in rats

Yamada, Tamaki; Marshall, Steven J.; Specian, Robert D.; Grisham, Matthew B.

doi:10.1016/0016-5085(92)91710-l

Cited by 237 publications

(122 citation statements)

References 17 publications

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“…MPO, an enzyme predominantly found in the azurophilics granules of neutrophils, is a biochemical marker of neutrophil infiltration, and its activity measurement has been widely used to detect intestinal inflammatory process. 28,29) Reduction of this enzyme activity can be interpreted as a manifestation of the anti-inflammatory property of a given compound. 25) Colonic tissue MPO activity, markedly elevated in TNBS control animals, was significantly decreased in rats pretreated with coumarin (5 mg/kg) and 4-hydroxycoumarin (25 mg/kg), suggesting an anti-inflammatory activity of these coumarins.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Luchini

Rodrigues-Orsi

Cestari

et al. 2008

Biological & Pharmaceutical Bulletin

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Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.

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Section: Discussionmentioning

confidence: 99%

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Luchini

Rodrigues-Orsi

Cestari

et al. 2008

Biological & Pharmaceutical Bulletin

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“…All animal treatments were performed according to a protocol approved by the Institutional Animal Care and Use Committee of Virginia Commonwealth University. The induction of chronic intestinal inflammation with TNBS was performed according to wellestablished methods (7,25,26,32,34,35). Briefly, rats were deeply anaesthetized with diethyl ether.…”

Section: Induction Of Chronic Intestinal Inflammation With Tnbs In Thmentioning

confidence: 99%

Endogenous IGF-I and α_vβ₃ integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis

Hazelgrove

Flynn²,

Qiao³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hazelgrove KB, Flynn RS, Qiao LY, Grider JR, Kuemmerle JF. Endogenous IGF-I and ␣v␤3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 296: G1230 -G1237, 2009. First published April 9, 2009 doi:10.1152/ajpgi.90508.2008.-Endogenous insulinlike growth factor-I (IGF-I) regulates intestinal smooth muscle growth by concomitantly stimulating proliferation and inhibiting apoptosis. IGF-I-stimulated growth is augmented by the ␣v␤3 integrin ligands vitronectin and fibronectin. IGF-I expression in smooth muscle is increased in both TNBS-induced colitis and Crohn's disease. We hypothesized that intestinal inflammation increased vitronectin and fibronectin expression by smooth muscle and, along with IGF-I upregulation, increased intestinal muscle growth. Intestinal smooth muscle cells were examined 7 days following the induction of TNBS-induced colitis. Although ␣ v␤3 integrin expression was not altered by TNBSinduced colitis, vitronectin and fibronectin levels were increased by 80 Ϯ 10% and 90 Ϯ 15%, above control levels, respectively. Basal IGF-I receptor phosphorylation in inflamed muscle from TNBStreated rats was increased by 86 Ϯ 8% over vehicle-treated controls. Basal ERK1/2, p70S6 kinase, and GSK-3␤ phosphorylation in muscle cells of TNBS-treated rats were also increased by 140 -180%. TNBS treatment increased basal muscle cell proliferation by 130 Ϯ 15% and decreased apoptosis by 20 Ϯ 2% compared with that in vehicletreated controls. The changes in proliferation and apoptosis were reversed by an IGF-I receptor tyrosine kinase inhibitor or an ␣v␤3 integrin antagonist. The results suggest that smooth muscle hyperplasia in TNBS-induced colitis partly results from the upregulation of endogenous IGF-I and ligands of ␣ v␤3 integrin that mediate increased smooth muscle cell proliferation and decreased apoptosis. This paper has identified one mechanism regulating smooth muscle hyperplasia, a feature of stricture formation that occurs in the chronically inflamed intestine of TNBS-induced colitis and potentially Crohn's disease.

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“…These include 1) marked increase in mucosal permeability and possible translocation of inflammatory mediators or infective organisms (9, 38); 2) neutrophil influx, MPO activity, and generation of superoxide radicals (39,40); 3) increased production of arachidonic metabolites, immunoreactive 6-ketoprostaglandin 1␣, leukotriene B 4 , or thromboxane B 2 (18,19,41). Although ACh may be the chief neurotransmitter in the enteric nervous system, it is also likely that other putative neurotransmitters may also be affected during inflammation such as tachykinins, as seen in colitis in canine or in humans (14,42).…”

Section: Colitis Inhibits Colonic Circular Musclementioning

confidence: 99%

Inflammation Inhibits Muscarinic Signaling in In Vivo Canine Colonic Circular Smooth Muscle Cells

Jadcherla

2002

Pediatr Res

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We investigated the effects of experimental colitis on the muscarinic signaling properties and contractile behavior of canine colonic circular smooth muscle. The hypotheses that inflammation 1) inhibits in vivo muscarinic receptor mediated contractions, and 2) alters receptor density or receptor-binding affinities were tested. Muscarine was infused close-intra-arterially in seven conscious dogs during normal and experimental colitis states. Colonic circular muscle contractions were recorded via surgically attached strain gauge transducers. Muscarine stimulated phasic contractions in a dose-dependent manner, whereas colitis was inhibited. The inhibitory concentration 50% dose of M 3 receptor inhibitor was several times lower than that of M 1 , M 2 , and M 4 inhibitors during normal and colitis. However, inflammation induced a significant leftward shift in the circular muscle inhibitory dose-response curve of M 2 inhibitor. Muscarinic receptor density and binding analyses in isolated circular muscle cells was done in normal and colitis states. Inflammation significantly decreased maximum binding from 4082 fmol/mg to 2708 fmol/mg, whereas affinity constant remained unaffected. The conclusions were that 1) spontaneous and muscarine-activated in vivo phasic contractile activity of colonic circular muscle cells is primarily mediated by M 3 receptors; 2) inflammation was associated with a shift in M 2 receptor potency, due chiefly to a decrease in receptor density; and 3) this inhibitory effect was seen in normal and inflamed states, suggesting the importance of M 2 receptor. These findings suggest that changes in muscarinic response during colitis may contribute to the abnormal motility seen with inflammatory bowel disease. ACh, the principal neurotransmitter of the enteric nervous system, is released not only as a result of parasympathetic activation, but also in response to many other gastrointestinal peptides (1). Atropine (nonselective muscarinic antagonist), when administered intravenously or close-intra-arterially (arterial) completely blocks all spontaneous smooth muscle contractions in the gut (1-3). In the gastrointestinal system, muscarinic receptors play a significant role in coordination of peristalsis and propulsion of luminal contents (4).The muscarinic receptors in the gut are localized at presynaptic, postsynaptic, and prejunctional and postjunctional sites (5). These receptors on smooth muscle cells mediate contractions by G-protein coupled mechanisms, whereas those at presynaptic and prejunctional sites modulate the release of ACh by negative feedback. The activation of muscarinic receptors at postsynaptic sites stimulates postsynaptic excitatory and inhibitory neurons to release neurotransmitters. The physiologic mechanisms by which muscarinic receptors stimulate in vivo colonic circular muscle contractions are not completely understood.

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A comparative analysis of two models of colitis in rats

Cited by 237 publications

References 17 publications

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Endogenous IGF-I and α_vβ₃ integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis

Inflammation Inhibits Muscarinic Signaling in In Vivo Canine Colonic Circular Smooth Muscle Cells

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A comparative analysis of two models of colitis in rats

Cited by 237 publications

References 17 publications

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Intestinal Anti-inflammatory Activity of Coumarin and 4-Hydroxycoumarin in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Endogenous IGF-I and αvβ3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis

Inflammation Inhibits Muscarinic Signaling in In Vivo Canine Colonic Circular Smooth Muscle Cells

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Endogenous IGF-I and α_vβ₃ integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis