ABSTRACT
AIM OF THE STUDY: This study assessed the involvement of endogenous glucocorticoids (GCs) in the anti-arthritic properties of bee venom (BV) on antigen-induced arthritis (AIA) in rabbits. MATERIALS AND METHODS: BV (1.5-6 microg/kg/day) was injected for 7 days before AIA induction, whereas the control group received sterile saline. The total and differential leukocyte count, PGE(2) levels in synovial fluid and synovial membrane cell infiltrate were evaluated. The contribution of GCs to BV action was assessed in rabbits treated with BV plus metyrapone, an inhibitor of GC synthesis, or RU-38 486, a steroid antagonist. RESULTS: Treatment with BV (1.5 microg/kg/day) reduced the leukocyte count and PGE(2) level (18571+/-1909 cells/mm(3) and 0.49+/-0.05 ng/mL, respectively) as well as the cellular infiltrate compared with the control group (40968+/-5248 cells/mm(3) and 2.92+/-0.68 ng/mL, p<0.05). The addition of metyrapone to BV treatment completely reversed the inhibition of AIA, whereas RU-38 486 was ineffective. CONCLUSION: Our data show that bee venom treatment prevents the development of antigen-induced arthritis in rabbits through the action of GCs.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antigens/administration & dosage , Arthritis, Experimental/drug therapy , Bee Venoms/pharmacology , Glucocorticoids/physiology , Animals , Anti-Inflammatory Agents/therapeutic use , Bee Venoms/therapeutic use , Dinoprostone/metabolism , Leukocyte Count , Metyrapone/administration & dosage , Mifepristone/administration & dosage , RabbitsABSTRACT
BACKGROUND: Our previous results showed that nitric oxide (NO) and bradykinin (BK) mediate the arthritis induced by Bothrops jararaca venom (BjV) in rabbits. In this study, we investigated the contribution of each receptor of BK as well as the inter-relationship between NO and eicosanoids in BjV-induced arthritis. METHODS: The arthritis was induced in rabbits with 16 microg of BjV injected intra-articularly. Prostaglandin E2 (PGE2), thromboxane B2 (TxB2), leukotriene B4 (LTB4) (radioimmunoassay) and nitrite/nitrate concentrations (NO2/NO3) (Griess reaction) were evaluated in the synovial fluid 4 h later. The animals were prior treated with NO synthase inhibitor (L-NAME; 20 mg/kg/day for 14 days), the B2 antagonist of BK (HOE-140) and the B1 antagonist of BK (des-Arg9[Leu8]-bradykinin), both at a dose of 0.3mg/kg, 30 min prior to the venom injection. RESULTS: Data show that L-NAME and HOE-140 treatment were equally able to reduce PGE2 and NO2/NO3 levels without interfering with TxB2 and LTB4 production. On the contrary, the B1 antagonist of BK inhibited TxB2 and LTB4 production, and did not alter PGE2 and NO metabolites levels in the inflamed joint. DISCUSSIONS: The results presented clarify the contribution of the kinin system, mainly through the B2 receptor, to the local inflammatory response induced by BjV, as well as its positive interaction with PGE2 and NO production.