Pharmacological evaluation of rat paw oedema induced byBothrops jararaca venom
- Cite this article as:
- Trebien, H.A. & Calixto, J.B. Agents and Actions (1989) 26: 292. doi:10.1007/BF01967293
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The mechanism involved in the genesis of the rat paw oedema caused by intraplantar (IPL) injection ofBothrops jararaca venom (BJV) has been investigated. IPL injection of BJV (1 to 30 μg/paw) caused a dose- and time-related oedematogenic effect. Oedema was maximal within 1 h after BJV injection, was partially reduced at 6 h and disappeared completely within 24 h. No systemic effect was observed. Previous heating of BJV at 100°C for 3 to 30 min caused a significant inhibition (25%) of its oedematogenic activity. Daily IPL injections of BJV (10 μg/paw) for 4 days attenuated BJV-induced oedema (26%), but did not influence oedema-induced by PAF-acether, serotonin (5-HT) and histamine (His), indicating the absence of cross desensitization. In the paw desensitized by daily IPL injections of PAF-acether, BJV induced a full oedematogenic response also indicating absence of cross desensitization. Different groups of drugs including α1- and α2-adrenoceptor antagonists (prazosin and yohimbine), inhibitors of both cyclo- and lipo-oxygenase (indomethacin, nordihydroguaiaretic acid), inhibitors of phospholiase A2 (dexamethasone and mepacrine) caused marked inhibition of BJV-induced rat paw oedema, whereas antagonists of 5-HT, PAF-acether and H1-histamine receptors were less effective. Pre-treatment with a β-adrenoceptor antagonist, a Ca2+ channel blocker and a H2-histamine antagonist failed to affect BJV-induced oedema. Pre-treatment of the animals with captopril did not interfere with BJV-induce oedema, suggesting that kinins are not insolved in the genesis of oedema. Association of BJV with 5-HT and PAF did not potentiate the BJV-induced oedema. It is concluded that BJV-induced rat paw oedema appears to be mediated primarily by cycloxygenase and lipoxygenase eicosanoid products and activation of α1- and α2-adrenoceptors, while HIS, 5-HT and PAF-acether appear to exert minor roles.