Caracterização dos efeitos inflamatorios induzidos pelo veneno bruto e pela LmTX-I de Lachesis muta muta (Surucucu) em ratos / Characterization of inflamatory effects induced by Lachesis muta muta (Surucucu) and LmTX-I in rats

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

The ability of crude venom and a basic phospholipase A2 (LmTX-I) from Lachesis muta muta venom to increase the microvascular permeability in the rat paw and skin has been investigated. Crude venom or LmTX-I were injected subplantarly or intradermically, after which oedema was measured at selected times thereafter. Paw volume was measured using a hydropletismometer, whereas skin extravasation at the skin sites was measured as accumulation of i.v. injected 125I-human serum albumin. Histamine liberation from rat mast cell was measured spectrofluorometrically. Crude venom (0.3-3 µg/paw) or LmTX-I (0.1-1 µg/paw) induced a dose-dependent rat paw oedema. Intradermal injection of crude venom (0.03-10 µg/site) or LmTX-I (0.003-0.3 µg/site) in the dorsal skin also resulted in dosedependent plasma extravasation. Crude venom-induced plasma extravasation was significantly inhibited by the histamine H1 receptor antagonist mepyramine (6 mg/kg), the histamine/5-hydroxytriptamine antagonist cyproheptadine (2 mg/kg), the nitric oxide synthesis inhibitor N?-L-nitro-arginine methyl ester (L-NAME; 100 nmol/site), the tachykinin NK1 receptor antagonist SR140333 (1 nmol/site), the bradykinin B2 receptor antagonist Icatibant (0.6 mg/kg) and the cyclooxygenase inhibitor indomethacin (5 mg/kg). The platelet-activating factor receptor antagonist PCA4248 (5 mg/kg) had no significant effect. LmTX-I-induced skin extravasation was significantly inhibited by cyproheptadine, mepyramine, indomethacin and PCA4248, while L-NAME, SR140333 and Icatibant had no effect. Additionally, both Lachesis muta muta venom and LmTX-I concentration-dependently induced histamine release from rat peritoneal mast cells. In conclusion, Lachesis muta muta venom and LmTX-I increase microvascular permeability by mechanisms involving mast cell activation and both had arachidonic acid metabolites participation. Crude venom-induced responses also involves substance P, bradykinin and nitric oxide release, whether LmTX-I-induced response involves PAF

ASSUNTO(S)

venenos de cobra mast cells lachesis muta muta permeabilidade vascular snake venon vascular permeability mastocitos

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