Neutralizacion de los efectos locales del veneno de Bothrops asper por un antiveneno polivalente

Gutiérrez, José Marı́a; Cháves, Fernando; Bolaños, Ronald Eduardo Díaz; Cerdas, Luis; Rojas, Ermila; Arroyo, Olga; Portilla, E.

doi:10.1016/0041-0101(81)90007-6

Cited by 102 publications

(36 citation statements)

References 8 publications

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“…Only when antivenom was injected before venom was neutralization achieved. In the case of B. asper venom, polyvalent antivenom produced in Costa Rica was ineffective in neutralizing edema or hyperalgesia when administered either before or after envenomation, in agreement with prior observations in mice (8,10). Moreover, Rucavado and Lomonte (24) demonstrated that the presence of antibodies in the circulation before injection of B. asper venom in mice reduces, but does not abolish, local tissue damage.…”

Section: Discussionsupporting

confidence: 75%

“…We selected venom doses which caused an increase in the sensitivity to pain (hyperalgesia) and local edema, without inducing macroscopically evident hemorrhage or tissue damage. Such doses have been validated and used in previous pharmacological stud- (8)(9)(10). It has been suggested that the observed poor neutralization is based on the fact that hyperalgesia and edema develop at an extremely rapid rate after venom injection, associated with the release of endogenous mediators involved in these pharmacological effects (15,16,25,26).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical investigations have demonstrated the efficacy of these products on the neutralization of life-threatening systemic effects associated with these envenomations (3,5,14). However, experimental and clinical evidence indicates that local effects in Bothrops sp envenomations are poorly neutralized by these and other antivenoms (3,8,10,13). The present results further demonstrate the complete ineffectiveness of these antivenoms in neutralizing the local edema and hyperalgesia induced by B. asper and B. jararaca venoms when antivenoms are administered to rats after envenomation.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental studies have suggested that there is significant, albeit partial, neutralization of hemorrhage, edema, dermonecrosis and myonecrosis only when antivenom is administered rapidly after envenomation (8)(9)(10), even when using antibody fragments F(ab') 2 and Fab which have a larger volume of distribution and reach the interstitial fluid at a faster rate (11,12). Clinical observations also indicate that local tissue damage is only partially halted by antivenoms (2,3,13).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

Picolo

Chacur

Gutiérrez

et al. 2002

Braz J Med Biol Res

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Neutralization of hyperalgesia induced by Bothrops jararaca and B. asper venoms was studied in rats using bothropic antivenom produced at Instituto Butantan (AVIB, 1 ml neutralizes 5 mg B. jararaca venom) and polyvalent antivenom produced at Instituto Clodomiro Picado (AVCP, 1 ml neutralizes 2.5 mg B. aspar venom). The intraplantar injection of B. jararaca and B. asper venoms caused hyperalgesia, which peaked 1 and 2 h after injection, respectively. Both venoms also induced edema with a similar time course. When neutralization assays involving the independent injection of venom and antivenom were performed, the hyperalgesia induced by B. jararaca venom was neutralized only when bothropic antivenom was administered iv 15 min before venom injection, whereas edema was neutralized when antivenom was injected 15 min or immediately before venom injection. On the other hand, polyvalent antivenom did not interfere with hyperalgesia or edema induced by B. asper venom, even when administered prior to envenomation. The lack of neutralization of hyperalgesia and edema induced by B. asper venom is not attributable to the absence of neutralizing antibodies in the antivenom, since neutralization was achieved in assays involving preincubation of venom and antivenom. Cross-neutralization of AVCP or AVIB against B. jararaca and B. asper venoms, respectively, was also evaluated. Only bothropic antivenom partially neutralized hyperalgesia induced by B. asper venom in preincubation experiments. The present data suggest that hyperalgesia and edema induced by Bothrops venoms are poorly neutralized by commercial antivenoms even when antibodies are administered immediately after envenomation. Correspondence

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

Picolo

Chacur

Gutiérrez

et al. 2002

Braz J Med Biol Res

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“…The minimum edema-forming (MED), hemorrhagic (MHD) and defibrinating (MDD) doses of B. atrox venom were determined by methods described elsewhere (6)(7)(8), and modified by Gutiérrez et al (9)(10)(11). Lethality (lethal dose 50%, LD 50 ) was determined by the Spearman-Karber method (12) using the ip route.…”

Section: Pharmacological Activities Of B Atrox Venommentioning

confidence: 99%

Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: comparison with two commercial antivenoms

Otero¹,

Núñez²,

Gutiérrez³

et al. 1997

Braz J Med Biol Res

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Three horse-derived antivenoms were tested for their ability to neutralize lethal, hemorrhagic, edema-forming, defibrinating and myotoxic activities induced by the venom of Bothrops atrox from Antioquia and Chocó (Colombia). The following antivenoms were used: a) polyvalent (crotaline) antivenom produced by Instituto Clodomiro Picado (Costa Rica), b) monovalent antibothropic antivenom produced by Instituto Nacional de Salud-INS (Bogotá), and c) a new monovalent anti-B. atrox antivenom produced with the venom of B. atrox from Antioquia and Chocó. The three antivenoms neutralized all toxic activities tested albeit with different potencies. The new monovalent anti-B. atrox antivenom showed the highest neutralizing ability against edema-forming and defibrinating effects of B. atrox venom (41 ± 2 and 100 ± 32 µl antivenom/mg venom, respectively), suggesting that it should be useful in the treatment of B. atrox envenomation in Antioquia and Chocó.

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Processing of pro‐tumor necrosis factor‐α by venom metalloproteinases: A hypothesis explaining local tissue damage following snake bite

Moura-da-Silva¹,

Laing²,

Paine³

et al. 1996

Eur J Immunol

138

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Venom-induced necrosis is a common local debilitating sequela of bites by many vipers, frequently resulting in severe permanent scarring and deformity. Antivenoms are not effective under these circumstances unless administered within a few minutes of the bite; this is unlikely to occur in the rural tropics where most victims take a long time to reach medical care. We have shown that two venom zinc metalloproteinases (jararhagin from Bothrops jararaca venom and a metalloproteinase from Echis pyramidum leakeyi venom) successfully cleaved the recombinant glutathione-S-transferase-tumor necrosis factor-alpha fusion protein (GST-TNF-alpha) substrate to form biologically active TNF-alpha which was shown to be neutralized by ovine TNF-alpha Fab antibodies. This resulted in a reduction of venom-induced necrosis in mice when injected intravenously or intradermally both before and after intradermal injections of E.p.leakeyi venom. A peptidomimetic (POL 647) was also found to inhibit the Echis metalloproteinase, thus preventing the processing of the TNF precursor; this was shown using a TNF-alpha-sensitive cell culture assay and electrophoresis. These observations demonstrate the possible importance of TNF-alpha in the development of the resulting necrotic lesion and leads to the hypothesis that increased levels of venom metalloproteinases following snake bite release active TNF-alpha. This cytokine may contribute to the local necrosis and also induce the production of endogenous matrix metalloproteinases, which in turn generate a positive feedback mechanism resulting in continued cleavage of pro-TNF-alpha. The results indicate that inhibition or neutralization of endogenous TNF-alpha appears to result in a significant reduction in venom-induced necrosis. This could help to explain the clinical observations that treatment of local necrosis following snake bite by antivenom is only minimally successful.

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Neutralizacion de los efectos locales del veneno de Bothrops asper por un antiveneno polivalente

Cited by 102 publications

References 8 publications

Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

Neutralizing capacity of a new monovalent anti-Bothrops atrox antivenom: comparison with two commercial antivenoms

Processing of pro‐tumor necrosis factor‐α by venom metalloproteinases: A hypothesis explaining local tissue damage following snake bite

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