Distribution and Anti‐inflammatory Effect of Mesalazine on Carrageenan‐induced Colitis in the Rabbit

Kitano, Atsuo; Matsumoto, Takayuki; Oshitani, Nobuhide; Nakagawa, M.; Yasuda, K; Watanabe, Yozo; Tomobuchi, M.; Ōbayashi, M.; Tabata, A; Fukushima, Ryuji; Okabe, H; Nakamura, Shirô; Obata, Akishige; Okawa, Kiyotaka; Kobayashi, Kenzo

doi:10.1111/j.1440-1681.1996.tb02828.x

Cited by 14 publications

(9 citation statements)

References 13 publications

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Effect of bucillamine on the trinitrobenzene sulfonic acid induced rat model of colitis 493 CD [7], however dose responsiveness was not confirmed by the present results. This might be due to relatively wide standard deviation of the colonic damage score in the group treated by 150mg/kg of bucillamine, or may indicate absence of dose responsiveness in the pharmacological efficacy of the agent [13].

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confidence: 82%

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Effect if bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis

Kitano¹,

Oshitani²,

Okabe³

et al. 1996

Inflamm Res

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Salicylazosulphapyridine and corticosteroids are the only remedies for inflammatory bowel disease currently in clinical use. They do not, however, necessarily bring about satisfactory therapeutic benefits, so that new agents are needed. In this study, we evaluated the effect of bucillamine, a new antirheumatic agent, in experimental rat colitis induced by trinitrobenzene sulfonic acid enema. Wistar rats were given vehicle alone (n = 16) or treated with 50 (n = 20) or 150 (n = 20) mg/kg of bucillamine daily for three weeks after induction of colitis. Conventional histological sections of the colon stained by haematoxylin and eosin were prepared and observed under a light microscope to determine colonic damage scores. The determinations were significantly lower in the group treated with 50 mg/kg of bucillamine and tended to be lower in the group treated with 150 mg/kg of bucillamine than in the untreated group, which implied that the experimentally induced colonic inflammatory changes and ulcerations were alleviated by bucillamine. Blood tests showed no abnormal values at the end of the treatment. The present observations suggest that bucillamine should be developed further as a possible therapy for inflammatory bowel disease.

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confidence: 82%

“…That bucillamine induced nephrotic syndrome aroused concern [14]. In carrageenan induced rabbit colitis, an elevation of BUN following sensitization was recognized in both of the bucillamine treated and untreated groups [7]. In the present experiment, however, such an abnormality in renal function was not noted.…”

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confidence: 64%

Effect if bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis

Kitano¹,

Oshitani²,

Okabe³

et al. 1996

Inflamm Res

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“…Cell proliferation, measured by increases in thymidine kinase activity, increased severalfold in the colon of rats when fed 5% degraded or undegraded CGN in solid food or water (4, 9, 41). Responding to concerns about the safety of CGN in the human diet, the European Union recently modified their recommendations with regard to incorporation of CGN in processed foods (8), endorsing a molecular weight limit of not more than 5% CGN below 50 kDa into the specification, to reduce exposure to degraded CGN.CGN causes a reproducible inflammatory reaction and remains a standard chemical for examining acute inflammation and effects of anti-inflammatory drugs (22,25). CGN-induced edema of rat hind paw has been an extensively used model of inflammation (42).…”

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confidence: 99%

“…CGN causes a reproducible inflammatory reaction and remains a standard chemical for examining acute inflammation and effects of anti-inflammatory drugs (22,25). CGN-induced edema of rat hind paw has been an extensively used model of inflammation (42).…”

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confidence: 99%

Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells

Borthakur

Bhattacharyya²,

Dudeja³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

140

153

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Borthakur A, Bhattacharyya S, Dudeja PK, Tobacman JK. Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 292: G829 -G838, 2007. First published November 9, 2006; doi:10.1152/ajpgi.00380.2006.-Carrageenan is a high molecular weight sulfated polygalactan used to improve the texture of commercial food products. Its use increased markedly during the last half century, although carrageenan is known to induce inflammation in rheumatological models and in intestinal models of colitis. We performed studies to determine its direct effects on human intestinal cells, including normal human intestinal epithelial cells from colonic surgeries, the normal intestinal epithelial cell line NCM460, and normal rat ileal epithelial cells. Cells were treated with high molecular weight -carrageenan at a concentration of 1 g/ml for 1-96 h. IL-8, IL-8 promoter activity, total and nuclear NF-B, IB␣, phospho-IB␣, and Bcl10 were assessed by immunohistochemistry, Western blot, ELISA, and cDNA microarray. Increased Bcl10, nuclear and cytoplasmic NF-B, IL-8 promoter activation, and IL-8 secretion were detected following carrageenan exposure. Knockdown of Bcl10 by siRNA markedly reduced the increase in IL-8 that followed carrageenan exposure in the NCM460 cells. These results show, for the first time, that exposure of human intestinal epithelial cells to carrageenan triggers a distinct inflammatory pathway via activation of Bcl10 with NF-B activation and upregulation of IL-8 secretion. Since Bcl10 contains a caspase-recruitment domain, similar to that found in NOD2/CARD15 and associated with genetic predisposition to Crohn's disease, the study findings may represent a link between genetic and environmental etiologies of inflammatory bowel disease. Because of the high use of carrageenan as a food additive in the diet, the findings may have clinical significance. inflammation; colon; NF-B; IB␣ CARRAGEENANS ARE HIGH MOLECULAR weight sulfated polygalactans derived from several species of red seaweeds (Rhodophyceae). The most common forms of carrageenan (CGN) are lambda (), kappa (), and iota (). CGN has alternating disaccharide units composed of D-galactose-2-sulfate and D-galactose-2,6-disulfate. CGN is composed predominantly of alternating D-galactose-4-sulfate and 3,6-anhydro-D-galactose residues. CGN varies from CGN by sulfation of the 3,6-anhydro-D-galactose at the second carbon. Galactose residues are joined by ␣-1,3 and ␤-1,4 linkages. CGNs resemble to some extent the naturally occurring glycosaminoglycans owing to their backbone composition of sulfated disaccharides. CGNs are extracted from specific seaweeds, including Gigartina, Chondrus, and Eucheuma, and are used by the food industry to improve the texture of food products by acting to thicken, stabilize, or emulsify dairy products, salad dressings, infant formulas, processed meat, soy milk, and other food products (37,38). In addition to incorporation in foods, CGN has been used a...

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“… 2–4 At a pharmacologically attainable concentration, bucillamine strongly suppresses B cell function. 5 We have recently found bucillamine to be effective in a model of colitis in rabbits 6 and rats 7 assessed by conventional histological methods. In the present study, we report on the efficacy of bucillamine in a rat model of colitis induced by hapten.…”

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confidence: 99%

Down‐regulation by Bucillamine of Lamina Propria Leucocytes in the Rat Colitis Model

Oshitani¹,

Matsumoto²,

Nakamura³

et al. 1999

Clin Exp Pharma Physio

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1. The efficacy of bucillamine has been reported in various inflammatory models. 2. In the present study, the effects of 2 weeks administration of bucillamine on hapten-induced experimental rat colitis were analysed. The gross morphological damage score was evaluated and the expression of CD4, CD8, CD11a, CD11b, CD25, CD54 and class II major histocompatibility complex (MHC) antigen was investigated by immunohistochemical methods. 3. Mean bodyweight was significantly increased in colitic rats given 750 micrograms bucillamine compared with colitic rats given vehicle (distilled water). Gross morphological damage was significantly less in colitic rats given 250 or 750 micrograms bucillamine compared with rats given vehicle. 4. Immunohistological studies revealed that CD4, CD11a, CD11b, CD54 and class II MHC antigen expression of infiltrating leucocytes was significantly lower in rat colonic mucosa treated with bucillamine. 5. From these findings, it appears that bucillamine may act through the down-regulation of the activation of lamina propria leucocytes in hapten-induced rat colitis.

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Distribution and Anti‐inflammatory Effect of Mesalazine on Carrageenan‐induced Colitis in the Rabbit

Cited by 14 publications

References 13 publications

Effect if bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis

Effect if bucillamine on the rat trinitrobenzene sulfonic acid induced model of colitis

Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells

Down‐regulation by Bucillamine of Lamina Propria Leucocytes in the Rat Colitis Model

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