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[Study the effect and mechanism of thalidomide in model of inflammatory bowed disease].
Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Jul; 36(4):548-51.SD

Abstract

OBJECTIVE

To assess the effect of thalidomide on Trinitrobenzensulphonic acid (TNBS)-induced or oxazolone-induced colitis and discuss the possible mechanism of its action.

METHODS

Transmural colitis was induced by TNBS in three groups of rats (n=6 each), and distal colitis was induced by oxazolone in three groups of rats (n=6 each). Then the rats of the groups were treated with thalidomide [200 mg/(kg x d)], prednisone [5 mg/(kg x d)] or vehicle (olive oil) respectively by oral gavage. The colitis was allowed to run its course for 7 d after gavage and at that time the following endpoints were assessed. Colitis was evaluated by macroscopic and microscopic score; the expression of NF-kappaB P65 was examined by immunohistchemical (IHC); the expression of TNF-alpha mRNA was assayed by hybridization in situ (ISH); the cytokine TNF-alpha, IL-4, IFN-gamma were estimated by enzyme-linked immunoadsordent assay (ELISA).

RESULTS

With respect to TNBS model, in the control, prednisone-treatment and thalidomide-treatment groups, the macroscopic and microscopic scores were 6.33 +/- 1.03, 1.67 +/- 0.82, 2.00 +/- 0.89 and 7.33 +/- 1.03, 2.67s +/- 0.82, 3.17 +/- 0.75 respectively; the expression levels of NF-kappaB P65 and TNF-alpha mRNA in the three groups were 62.45 +/- 12.38, 23.62 +/- 8.54, 34.18 +/- 9.65 and 12.42 +/- 4.63, 9.86 +/- 3.29, 4.35 +/- 1.74 respectively; the levels of TNF-alpha, IL-4, IFN-gamma were 540.32 +/- 80.76, 94.58 +/- 14.45, 486.18 +/- 68.47; 396.53 +/- 92.42, 78.45 +/- 12.69, 347.56 +/- 82.94; and 385.68 +/- 88.57, 123.68 +/- 38.15, 378.27 +/- 90.65 respectively. The results indicated that thalidomide treatment significantly reduced colonic inflammation, suppressed NF-kappaB activation,enhanced TNF-alpha mRNA degradation, inhibited the synthesis of the TNF-alpha, IEN-gamma and increased the production of IL-4. However, with respect to oxazolone model, the macroscopic score and microscopic score were 2.00 +/- 0.89, 0.33 +/- 0.52, 1.83 +/- 0.75 and 7.83 +/- 1.47, 3.33 +/- 0.82, 6.50 +/- 1.22 respectively. Thalidomide appeared not to be effective in reducing the oxazolone-induced chronic colitis.

CONCLUSION

Thalidomide may be proposed as a useful drug for Crohn's disease, but further work is needed to clarify whether it is an efficacious agent for ulcerative colitis.

Authors+Show Affiliations

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.No affiliation info available

Pub Type(s)

English Abstract
Journal Article

Language

chi

PubMed ID

16078585

Citation

Wang, Xuan, and Qin Ouyang. "[Study the Effect and Mechanism of Thalidomide in Model of Inflammatory Bowed Disease]." Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition, vol. 36, no. 4, 2005, pp. 548-51.
Wang X, Ouyang Q. [Study the effect and mechanism of thalidomide in model of inflammatory bowed disease]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005;36(4):548-51.
Wang, X., & Ouyang, Q. (2005). [Study the effect and mechanism of thalidomide in model of inflammatory bowed disease]. Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition, 36(4), 548-51.
Wang X, Ouyang Q. [Study the Effect and Mechanism of Thalidomide in Model of Inflammatory Bowed Disease]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005;36(4):548-51. PubMed PMID: 16078585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Study the effect and mechanism of thalidomide in model of inflammatory bowed disease]. AU - Wang,Xuan, AU - Ouyang,Qin, PY - 2005/8/5/pubmed PY - 2006/2/4/medline PY - 2005/8/5/entrez SP - 548 EP - 51 JF - Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition JO - Sichuan Da Xue Xue Bao Yi Xue Ban VL - 36 IS - 4 N2 - OBJECTIVE: To assess the effect of thalidomide on Trinitrobenzensulphonic acid (TNBS)-induced or oxazolone-induced colitis and discuss the possible mechanism of its action. METHODS: Transmural colitis was induced by TNBS in three groups of rats (n=6 each), and distal colitis was induced by oxazolone in three groups of rats (n=6 each). Then the rats of the groups were treated with thalidomide [200 mg/(kg x d)], prednisone [5 mg/(kg x d)] or vehicle (olive oil) respectively by oral gavage. The colitis was allowed to run its course for 7 d after gavage and at that time the following endpoints were assessed. Colitis was evaluated by macroscopic and microscopic score; the expression of NF-kappaB P65 was examined by immunohistchemical (IHC); the expression of TNF-alpha mRNA was assayed by hybridization in situ (ISH); the cytokine TNF-alpha, IL-4, IFN-gamma were estimated by enzyme-linked immunoadsordent assay (ELISA). RESULTS: With respect to TNBS model, in the control, prednisone-treatment and thalidomide-treatment groups, the macroscopic and microscopic scores were 6.33 +/- 1.03, 1.67 +/- 0.82, 2.00 +/- 0.89 and 7.33 +/- 1.03, 2.67s +/- 0.82, 3.17 +/- 0.75 respectively; the expression levels of NF-kappaB P65 and TNF-alpha mRNA in the three groups were 62.45 +/- 12.38, 23.62 +/- 8.54, 34.18 +/- 9.65 and 12.42 +/- 4.63, 9.86 +/- 3.29, 4.35 +/- 1.74 respectively; the levels of TNF-alpha, IL-4, IFN-gamma were 540.32 +/- 80.76, 94.58 +/- 14.45, 486.18 +/- 68.47; 396.53 +/- 92.42, 78.45 +/- 12.69, 347.56 +/- 82.94; and 385.68 +/- 88.57, 123.68 +/- 38.15, 378.27 +/- 90.65 respectively. The results indicated that thalidomide treatment significantly reduced colonic inflammation, suppressed NF-kappaB activation,enhanced TNF-alpha mRNA degradation, inhibited the synthesis of the TNF-alpha, IEN-gamma and increased the production of IL-4. However, with respect to oxazolone model, the macroscopic score and microscopic score were 2.00 +/- 0.89, 0.33 +/- 0.52, 1.83 +/- 0.75 and 7.83 +/- 1.47, 3.33 +/- 0.82, 6.50 +/- 1.22 respectively. Thalidomide appeared not to be effective in reducing the oxazolone-induced chronic colitis. CONCLUSION: Thalidomide may be proposed as a useful drug for Crohn's disease, but further work is needed to clarify whether it is an efficacious agent for ulcerative colitis. SN - 1672-173X UR - https://www.unboundmedicine.com/medline/citation/16078585/[Study_the_effect_and_mechanism_of_thalidomide_in_model_of_inflammatory_bowed_disease]_ DB - PRIME DP - Unbound Medicine ER -