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. 2002 Nov;61(Suppl 2):ii19–ii24. doi: 10.1136/ard.61.suppl_2.ii19

Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitis

R Boismenu, Y Chen, K Chou, A El-Sheikh, R Buelow
PMCID: PMC1766705  PMID: 12379615

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Figure 1 .

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Orally administered RDP58 reduces the severity of clinical symptoms during acute DSS colitis. Severity of colitis in DSS treated mice (n= 4) and DSS treated mice receiving RDP58 (n= 4). Results are expressed as the mean clinical activity scores for each group. Control groups included mice kept on regular drinking water and mice receiving regular water and given RDP58 by gavage. A higher value indicates more severe disease. Control groups including those receiving RDP58 in the absence of DSS treatment had a clinical activity scores between 0 and 1 (data not shown). The data shown are representative of three separate experiments.

Figure 2 .

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RDP58 dramatically lessens macroscopic evidence of DSS induced colonic damage. Representative colon from a control untreated mouse (left), a mouse fed DSS for six days (middle), and from a DSS treated mouse given RDP58 (right). The colon from DSS treated mice showed evidence of atrophy and profuse bleeding. In contrast, the colon from DSS treated mice receiving RDP58 remained relatively normal.

Figure 3 .

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Histological presentation of colitis in DSS treated mice and protective effect of orally administered RDP58 (Allotrap 1258). (A) RDP58 preserves the architecture and minimises ulceration of the colon in DSS treated mice. Representative histology from the colon of a control untreated mouse (top panel), a mouse fed DSS for six days (middle panel), and from a DSS treated mouse given RDP58 (bottom panel). Original magnifications x200. (B) Quantitative analysis of crypt damage. The crypt damage score is described in "Materials and methods" and by Boismenu and Chen20. *p<0.0001 compared with DSS treated mice.

Figure 4 .

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RDP58 inhibits TNF production in the colon of DSS treated mice. (A) TNF mRNA expression was evaluated by RT-PCR as described in "Materials and methods", and the data were measured with a fluorescence imager (Molecular Dynamics, CA). *p<0.05 compared with control mice and **p<0.005 when compared with DSS treated mice. (B) TNF protein expression was measured from 18 hour culture supernatants of colon biopsy specimens as described in "Materials and methods". *p<0.05 when compared with DSS treated mice. Original magnification x200.

Figure 5 .

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RDP58 reduces neutrophil infiltration in the colon of DSS treated mice. Tissue myeloperoxidase content was measured from colon samples removed from mice killed six days after initiation of DSS treatment as described in "Materials and methods". *p<0.05 compared with DSS treated mice. Comparison of values between DSS treated mice given RDP58 and control mice showed no significant differences.

Figure 6 .

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RDP58 preserves colonic epithelial cell proliferation in DSS treated mice. Epithelial cell proliferation was measured by in vivo BrdU administration as described in "Materials and methods". *p<0.01 compared with DSS treated mice.

Figure 7 .

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RDP58 blocks colonic epithelial cell apoptosis in DSS treated mice. Apoptosis was evaluated by the TUNEL assay as described in "Materials and methods". Representative TUNEL stained sections from the colon of a control untreated mouse (top panel), a mouse fed DSS for six days (middle panel), and from a DSS treated mouse given RDP58 (bottom panel). Original magnifications x200.

Selected References

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