| Autor: |
Weithmann, K. U., Schlotte, V., Jeske, V., Seiffge, D., Laber, A., Haase, B., Schleyerbach, R. |
| Zdroj: |
Inflammation Research; Jul1997, Vol. 46 Issue 7, p246-252, 7p |
| Abstrakt: |
Objective and Design: To study the effects of tiaprofenic acid and doxycycline on urinary pyridinium crosslinks and paw swelling in adjuvant arthritic rats, and to gain additional information on the drugs' inhibitory potential vs. in vitro targets, such as enzyme activity of matrix metalloproteinases and cytokine generation.¶ Material: 124 male Wistar Lewis rats; for the in vitro studies human matrix metalloproteinases and human mononuclear cells were used.¶ Treatment: Arthritis was induced by injection of complete Freund adjuvant. Drugs (2, 15, 50 mg tiaprofenic acid/kg; 5, 15, 30 mg doxycycline/kg) were administered daily p.o. until day 21. In the in vitro studies 10-1000 mmoles/l of these drugs were used.¶ Methods: Urinary levels of pyridinoline and deoxypyridinoline, determined by HPLC/fluorescence, and paw volumes were the measurements in the rat study. In the in vitro studies enzyme activities were assessed using fluorogenic peptide substrates; cytokines were determined by ELISA.¶ Results: On day 21 of disease crosslink excretion was about twofold higher compared to the healthy controls. After administering daily 15 or 30 mg/kg tiaprofenic acid p.o. this increase was almost completely prevented whereas the paw volumes were suppressed by about 50%. Up to 50 mg/kg doxycycline did not display significant suppressive effects on crosslinks and paw volumes. In vitro 50-100 μmol/l of both drugs inhibited the activities of selected metalloproteinases, but only doxycycline suppressed the generation of IL-1β/TNFα in human mononuclear cells, whereas tiaprofenic acid was virtually inactive in that model.¶ Conclusions: In arthritic rats tiaprofenic acid has not only the capability to suppress paw inflammation, but also to prevent with high potency the excretion of pyridinium crosslinks. Doxycycline without inherent antiinflammatory activity does not exhibit such preserving effects on collagen degradation in this model. Thus the mode of action of cartilage protecting drugs within the complex pathogenesis of arthritis will need further elucidation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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