Specific type IV phosphodiesterase inhibitor rolipram mitigates experimental colitis in mice.

Details

Serval ID
serval:BIB_BB160EA214F8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Specific type IV phosphodiesterase inhibitor rolipram mitigates experimental colitis in mice.
Journal
Journal of Pharmacology and Experimental Therapeutics
Author(s)
Hartmann G., Bidlingmaier C., Siegmund B., Albrich S., Schulze J., Tschoep K., Eigler A., Lehr H.A., Endres S.
ISSN
0022-3565 (Print)
ISSN-L
0022-3565
Publication state
Published
Issued date
2000
Volume
292
Number
1
Pages
22-30
Language
english
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
The specific type IV phosphodiesterase inhibitor rolipram is a potent suppressor of tumor necrosis factor-alpha (TNF) synthesis. We examined the efficacy of rolipram for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulfate sodium in their drinking water continuously for up to 11 days. Colitis was quantified by a clinical activity score assessing weight loss, stool consistency, and rectal bleeding (range from 0 to 4); by colon length; by a semiquantitative histologic score (range from 0 to 6); and by detecting TNF concentration in colonic tissue by enzyme-linked immunosorbent assay. In a first protocol, rolipram (10 mg/kg b.wt./day i.p.) was started on the same day as dextran sulfate sodium. Rolipram reduced the clinical activity of colitis (score 1.1 +/- 0.3) compared with mice that did not receive rolipram (2.4 +/- 0.4; P =.041). Rolipram also partially reversed the reduction of colon length (without rolipram, 12.4 +/- 0. 3 cm; with rolipram, 15.4 +/- 0.7 cm; P =.004) and improved the histologic score (1.5 +/- 0.6 in rolipram-treated mice versus 4.6 +/- 0.5; P =.020). Rolipram suppressed colonic tissue TNF concentrations. The beneficial effect of rolipram was confirmed in a second protocol in which dextran sulfate sodium exposure was discontinued on day 7 and rolipram was administered from day 8 through day 15. These three series of experiments on a total of 153 mice documented the efficacy of rolipram in both the prevention and treatment of experimental colitis.
Keywords
Animals, Body Weight/drug effects, Colitis/chemically induced, Colitis/drug therapy, Dextran Sulfate, Feces/chemistry, Female, Hemorrhage/chemically induced, Mice, Mice, Inbred BALB C, Phosphodiesterase Inhibitors/pharmacology, Rolipram/pharmacology, Time Factors, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Create date
25/11/2011 19:50
Last modification date
20/08/2019 15:29
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