Mediação química da hiperagesia induzida pelos venenos de serpentes Bothrops jararaca e Bothrops asper e por uma miotoxina com atividade de fosfolipase A2 isolada do veneno de Bothrops asper / Chemical mediation of hyperalgesia induced by Bothrops jararaca and Bothrops asper snake venoms and by a phospholipase A2 miotoxin isolated from Bothrops asper venom.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2000

RESUMO

Bothrops venoms cause pronounced local tissue-damage characterized by hemorrhage, myonecrosis, edema and pain. Venom-induced pain has been poorly investigated, despite its clinical relevance. Furthermore, the ability of antivenom to neutralize hyperalgesia induced by these venoms is not known. In the present study the hyperalgesia and edema induced by Bothrops jararaca (BjV) and Bothrops asper (BaV) venom and by myotoxin III-MIII (Asp49- phospholipase A2), a toxin isolated from BaV, were investigated. The chemical mediators involved in these phenomena and the ability of the antivenom to neutralize the hyperalgesia and edema induced by these venoms were also investigated. Pain threshold was assessed before and at several intervals after venom injection, using the rat paw pressure test. Edema of paw was measured phethysmographically at the same periods of time. The intraplantar injection of BjV (5µg/paw), BaV (15µg/paw) or MIII (10µg/paw) caused hyperalgesia and edema, whose peak were observed at the 1st (BjV, MIII) or 2nd (BaV) hours after venom/toxin administration, decreasing thereafter. For neutralization studies, the antivenoms produced either at Instituto Butantan from Brazil (AVIB) or Instituto Clodomiro Picado from Costa Rica (AVCP) were administered intravenously 15 min prior to, or immediately before, or 15 min after venoms injection. When the antivenom from Instituto Butantan was injected 15 min. before BjV, the hyperalgesia and edema were abolished. Furthermore, partial inhibition of edema was also observed when the antivenom was injected together with BjV. On the other hand, hyperalgesia and edema induced by BaV were not modified by AVCP. Incubation of BjV and BaV, for 30 min. at 37oC, with the antivenoms in vitro, abolished the hyperalgesia and edema. The inability of the in vivo treatment with antivenom in abolishing hyperalgesia and edema induced by BaV seems not to be related to the lack of neutralizing antibodies in antivenom, because neutralization was achieved in pre-incubation experiments. In order to investigate the chemical mediation of hyperalgesia and edema induced by the venoms or toxin, animals were treated with several drugs. Pretreatment with Hoe-140, dexamethasone and NDGA blocked the hyperalgesia induced by BaV, whereas only promethazine reduced the edema induced by this venom. The MIII-induced hyperalgesia was blocked by promethazine, methysergide, Hoe-140, dexamethasone and NDGA, whereas the edema was reduced only by promethazine and dexamethasone. These results suggest that: a) MIII may contribute to the BaV-induced hyperalgesia, b) bradykinin and leukotrienes mediate the BaV- and MIII-induced pain and MIII; c) histamine and serotonin also participate in the myotoxin-induced hyperalgesia and d) the edema induced by BaV and MIII is mediated by histamine. Pre-treatment of the animals with Hoe-140 abolished BjV-induced hyperalgesia, suggesting that bradykinin may mediate the venom-induced hyperalgesia. However, this treatment did not modify the BjV-induced edema. It is important to stress that previous studies have shown that BjV-induced hyperalgesia is mediated, at least partially, by eicosanoids and PAF (TEIXEIRA et al.,1994). The data presented herein also suggest that distinct mechanisms may be involved in the development of hyperalgesia and edema induced by both venoms and myotoxin III.

ASSUNTO(S)

hyperalgesia asp-49 phospholipase a2 bothrops asper venom hiperalgesia veneno de bothrops jararaca bothrops jararaca venom oedema asp 49 - fosfolipase a2 veneno de bothrops asper edema

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