Anti-inflammatory synergy of MEN16132, a kinin B2 receptor antagonist, and dexamethasone in carrageenan-induced knee joint arthritis in rats
| Autor: | Sandro Giuliani, Claudio Valenti, Manuela Tramontana, C.A. Maggi, Cecilia Cialdai |
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| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
Pharmacology medicine.medical_specialty Bradykinin B2 Receptor Antagonists medicine.drug_class business.industry Arthritis Bradykinin Kinin medicine.disease Anti-inflammatory Carrageenan chemistry.chemical_compound Endocrinology chemistry Internal medicine medicine B2 Bradykinin Receptor business Dexamethasone medicine.drug |
| Zdroj: | British Journal of Pharmacology. 161:1616-1627 |
| ISSN: | 0007-1188 |
| Popis: | BACKGROUND AND PURPOSE Bradykinin, through its B2 receptor, is involved in inflammatory processes related to arthropathies. In carrageenan and lipopolysaccharide (LPS)-induced arthritis in rat, the anti-inflammatory activity of MEN16132, a potent and selective kinin B2 receptor antagonist, was compared with that of steroidal and nonsteroidal anti-inflammatory drugs. The interaction between MEN16132 and dexamethasone was also investigated. EXPERIMENTAL APPROACH Drugs, alone or in combination, were injected into the knee joint 30 min before intra-articular administration of carrageenan or LPS, in pentobarbital anaesthetized rats. Effects on incapacitation, oedema, neutrophil recruitment and kallikrein system activation, in the knee joint, were assessed. KEY RESULTS MEN16132 and dexamethasone (10–300 µg per knee) dose-dependently reduced carrageenan-induced joint pain, oedema and neutrophil infiltration, reaching a maximal inhibition of about 50%. Dexketoprofen exerted a similar analgesic activity, whereas it did not affect the other inflammatory responses. MEN16132 showed a partial inhibition of LPS-induced joint pain, whereas dexamethasone produced a full analgesic effect. Combination of MEN16132 and dexamethasone showed a strong synergistic interaction in inhibiting both carrageenan and LPS-induced knee joint inflammation. Dexamethasone did not prevent the contact activation of prekallikrein by carrageenan and the subsequent release of kallikreins and bradykinin in the synovium. CONCLUSIONS AND IMPLICATIONS Steroids and kinin B2 receptor antagonists appear to relieve arthritic symptoms induced by carrageenan or LPS and act synergistically to inhibit joint inflammation. This could have interesting therapeutic implications, possibly opening the way for combination therapies in the control of inflammatory arthropathies. |
| Databáze: | OpenAIRE |
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