Inflammatory mediators of experimental colitis in rats

Rachmilewitz, Daniel; Simon, P L; Schwartz, Lester W.; Griswold, Don E.; Fondacaro, Joseph D.; Wasserman, Martin A.

doi:10.1016/0016-5085(89)90068-1

Cited by 242 publications

(101 citation statements)

References 21 publications

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“…Increased macroscopic colitis score (ulcer score), ulcer area and ulcer index with marked erythema of the colonic wall indicate mucosal damage and ulceration due to AA (Table 2 and Figure 3). The significant increase in wet weight of the colon and colon w/L ratio reflect the severity of UC, degree of inflammation, swelling, thickening of intestinal walls due to ulceration (Thippeswamy et al 2011;Rachmilewitz et al 1989) and suggest the inflammatory nature of AA-induced UC. This is further evident from histopathological observations (Table 4 and Figure 5) and confirmed the AA-induced inflammatory changes and necrosis of tissue as mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Dey

Sharma

Wanjari

et al. 2016

Pharmaceutical Biology

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Context: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders. Objective: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats. Materials and methods: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon. Results: APME or APAE pretreatment significantly (p < .05-.001) prevented AA-induced reduction in body weight and increase in colitis parameters viz. stool consistency, colon weight/length ratio and ulcer score, area and index. Extracts treatment attenuated (p < .001) increase in alkaline phosphatase and lactate dehydrogenase in serum and myeloperoxidase activity and cytokines in colon tissue due to AA administration. Extracts treatment prevented AA-induced elevation in lipid peroxidation and decline in activities of superoxide dismutase and catalase and reduced-glutathione content (p < .05-.001) along with histopathological alterations. PRDS also showed similar ameliorative effect on colitis. Discussion and conclusion: APME and APAE showed a preventive effect on UC, and ameliorated inflammation and oxidative damage in colon. The effects may be attributed to presence of phytochemicals, betulinic acid, b-sitosterol, and glucomannan. In conclusion, the tuber of Amorphophallus paeoniifolius exhibited an anticolitic effect through anti-inflammatory and antioxidant action. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Dey

Sharma

Wanjari

et al. 2016

Pharmaceutical Biology

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“…Tissue MPO activity was determined by a standard enzymatic procedure as described previously, 17 with minor modifications. Briefly, after the samples were weighed, a tissue sample (approximately 300 mg) was homogenized in a buffer (0.5% hexadecyltrimethylammonium bromide in 50 mM potassium phosphate buffer, pH 6.0) three times for 30 s each on ice.…”

Section: Measurement Of Myeloperoxidase Activitymentioning

confidence: 99%

Protective role of tumor necrosis factor (TNF) receptors in chronic intestinal inflammation: TNFR1 ablation boosts systemic inflammatory response

Wang¹,

Han²,

Chen³

et al. 2013

Laboratory Investigation

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Tumor necrosis factor-a (TNF-a) acts as a key factor for the development of inflammatory bowel diseases (IBDs), whose function is known to be mediated by TNF receptor 1 (TNFR1) or TNFR2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, chronic colitis was established by oral administration of dextran sulfate sodium (DSS) in TNFR1 or TNFR2 À / À mice. Unexpectedly, TNFR1 or TNFR2 deficiency led to exacerbation of signs of colitis compared with wild-type (WT) counterparts. Of note, TNFR1 ablation rendered significantly increased mortality compared with TNFR2 and WT mice after DSS. Aggravated pathology of colitis in TNFR1 À / À or TNFR2 À / À mice correlated with elevated colonic expression of proinflammatory cytokines and chemokines. Importantly, ablation of TNFR1 or TNFR2 increased apoptosis of colonic epithelial cells, which might be due to the heightened ratio of Bax/Bcl-2 and increased expression of caspase-8. Intriguingly, despite comparable intensity of intestinal inflammation in TNFR-deficient mice after DSS, systemic inflammatory response (including splenomegaly and myeloid expansion) was augmented dramatically in TNFR1 À / À mice, instead of TNFR2 À / À mice. Granulocyte macrophage colony-stimulating factor (GMCSF) was identified as a key mediator in this process, as neutralization of GMCSF dampened peripheral inflammatory reaction and reduced mortality in TNFR1 À / À mice. These data suggest that signaling via TNFR1 or TNFR2 has a protective role in chronic intestinal inflammation, and that lacking TNFR1 augments systemic inflammatory response in GMCSF-dependent manner.

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“…Thus, stimulated inflammatory cells present in the inflamed mucosa are capable of producing superoxide anion and hydrogen peroxide (Harris et al, 1992;McKenzie et al, 1996;Simmonds and Rampton, 1993).The xantine oxidase pathway and the oxidation of arachidonic acid in colonocytes constitute additional sources of ROS (Biemond et al, 1988;Markowitz et al, 1988;Sedghi et al, 1993). The interaction of these species with specific vascular or interstitial components yield potent chemoattractants for inflammatory phagocytes, establishing a self-amplifying cycle of ROS production that may overwhelm defense strategies resulting in tissue damage (Lewis et al, 1988;Shingu and Nobunaga 1984;Zimmerman et al, 1990).One of the most commonly used experimental models of IBD is the administration of an enema containing the contact-sensitizing allergen trinitrobenzenesulfonic acid (TNBS) in ethanol resulting in the development of macroscopic, histologic, and biochemical alterations that are well-characterized (Rachmilewitz et al, 1989;Wallace, 1988;Wallace et al, 1989). Although the mechanisms whereby TNBS cause an inflammatory response are not completely defined, this response is thought to be initiated by macrophagemediated recognition and degradation of the TNBSmodified cells and proteins within the colonic interstitium (Grisham et al, 1991;Kunin and Gallily, 1983).…”

mentioning

confidence: 99%

“…One of the most commonly used experimental models of IBD is the administration of an enema containing the contact-sensitizing allergen trinitrobenzenesulfonic acid (TNBS) in ethanol resulting in the development of macroscopic, histologic, and biochemical alterations that are well-characterized (Rachmilewitz et al, 1989;Wallace, 1988;Wallace et al, 1989). Although the mechanisms whereby TNBS cause an inflammatory response are not completely defined, this response is thought to be initiated by macrophagemediated recognition and degradation of the TNBSmodified cells and proteins within the colonic interstitium (Grisham et al, 1991;Kunin and Gallily, 1983).…”

mentioning

confidence: 99%

Replenishment of Glutathione Levels Improves Mucosal Function in Experimental Acute Colitis

Ardite

Sans

Panés

et al. 2000

Laboratory Investigation

107

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SUMMARY:Because reactive oxygen species (ROS) have been implicated as mediators of inflammatory bowel disease (IBD), the purpose of the present work was to determine the functional role of mucosal GSH in the trinitrobenzenesulfonic acid in 50% ethanol (TNBSϩethanol)-induced colitis in rats. Mucosal samples were taken to evaluate the temporal relationship between the extent of injury, the levels of glutathione (GSH) during acute colitis induced by TNBSϩethanol, and the effect of N-acetylcysteine (NAC) administration. In vitro assays revealed the interaction of TNBS with GSH leading to the almost instantaneous disappearance of GSH, while the reductive metabolism of TNBS by GSSG reductase generated ROS. Mucosal samples from TNBSϩethanol-treated rats indicated a direct correlation between GSH depletion and injury detected as soon as 30 minutes after TNBSϩethanol administration that persisted 24 hours post treatment. Although, short term depletion of mucosal GSH per se by diethylmaleate did not result in mucosal injury, the oral administration of NAC (40 mM) 4 hours after TNBSϩethanol treatment increased GSH stores (2-fold), decreasing the extent of mucosal injury (60 -70%) examined at 24 hours post treatment. However, an equimolar dose of dithiothreitol failed to increase GSH levels and protect mucosa from TNBSϩethanol-induced injury. Interestingly, GSH levels in TNBSϩethanol-treated rats recovered by 1-2 weeks, an effect that was accounted for by an increase of ␥-glutamylcysteine synthetase (␥-GCS) activity due to an induction of ␥-GCS-heavy subunit chain mRNA. Thus, TNBS promotes two independent mechanisms of injury, GSH depletion and ROS generation, both being required for the manifestation of mucosal injury as GSH limitation renders intestine susceptible to the TNBS-induced ROS overgeneration. Accordingly, in vivo administration of NAC attenuates the acute colitis through increased mucosal GSH levels, suggesting that GSH precursors may be of relevance in the acute relapse of IBD. (Lab Invest 2000, 80:735-744).I nflammatory bowel disease (IBD) is a chronic inflammatory disorder whose etiology is not completely understood. Several factors are recognized to contribute to its development including an overgeneration of reactive oxygen species (ROS). Production of ROS from several sources initiate a cytotoxic cascade of events that culminate in cell death. Thus, stimulated inflammatory cells present in the inflamed mucosa are capable of producing superoxide anion and hydrogen peroxide (Harris et al, 1992;McKenzie et al, 1996;Simmonds and Rampton, 1993).The xantine oxidase pathway and the oxidation of arachidonic acid in colonocytes constitute additional sources of ROS (Biemond et al, 1988;Markowitz et al, 1988;Sedghi et al, 1993). The interaction of these species with specific vascular or interstitial components yield potent chemoattractants for inflammatory phagocytes, establishing a self-amplifying cycle of ROS production that may overwhelm defense strategies resulting in tissue damage (Lewis et al, 1988;Shingu and ...

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Inflammatory mediators of experimental colitis in rats

Cited by 242 publications

References 21 publications

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Protective role of tumor necrosis factor (TNF) receptors in chronic intestinal inflammation: TNFR1 ablation boosts systemic inflammatory response

Replenishment of Glutathione Levels Improves Mucosal Function in Experimental Acute Colitis

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