Comparative study on the ability of IgG and Fab sheep antivenoms to neutralize local hemorrhage, edema and myonecrosis induced by Bothrops asper (terciopelo) snake venom (original) (raw)
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Toxicon, 2000
The ability of sheep antivenoms, consisting of whole IgG molecules or Fab fragments, to neutralize local hemorrhage, edema and myonecrosis induced by Bothrops asper venom was comparatively studied in mice. The two antivenoms were produced from the same batch of hyperimmune plasma and were adjusted to the same neutralizing potency against these eects in assays where venom and antivenoms were incubated prior to injection. Thus, if dierences are observed in experiments involving independent injection of venom and antivenoms, they would depend on the pharmacokinetic pro®les of the products. Despite the observation that both antivenoms neutralized the three eects if preincubated with venom, neutralization was only partial when antivenoms were administered i.v. at various time intervals after envenomation. No signi®cant dierences were observed between IgG and Fab antivenoms concerning neutralization of hemorrhagic and edema-forming activities, whereas IgG antivenom was slightly more eective in neutralizing myotoxic activity in experiments involving independent injection of venom and antivenom. These results do not support the hypothesis that Fab fragments are more eective than whole IgG molecules in the neutralization of locally-acting toxins from B. asper venom. #
Toxicon, 2001
Whole IgG and F(ab H) 2 equine-derived polyvalent (Crotalinae) antivenoms, prepared from the same batch of hyperimmune plasma, were compared in terms of neutralization of the lethal and de®brinating activities induced by Bothrops asper venom, their ability to reach the muscle tissue compartment in envenomated mice, and their potential for the induction of adverse reactions. Both preparations were adjusted to the same potency against the lethal effect of B. asper venom in experiments involving preincubation of venom and antivenom. Then, ªrescueº experiments were performed, i.e. antivenom was administered either intravenously or intramuscularly at various times after envenomation. IgG and F(ab H) 2 antivenoms were equally effective in the neutralization of lethality, both being more effective when administered i.v. than after i.m. injection. Neutralization decreased as the time lapse between envenomation and treatment increased. No signi®cant differences were observed in the ability of antivenoms to neutralize de®brinating activity of B. asper venom in experiments involving independent injection of venom and antivenoms. There was a much higher accumulation of equine antibodies in muscle tissue that had been injected with B. asper venom than in non-envenomated tissue, indicating that venom-induced microvessel damage probably favors a prominent and similar extravasation of both IgG and F(ab H) 2 antibodies. This may explain the similar effectiveness of both types of antivenom in previously reported studies on the neutralization of venom-induced local tissue damage. Both IgG and F(ab H) 2 antivenoms activate human complement in vitro and induce an anti-equine immunoglobulin response in mice, indicating that Fc removal per se does not eliminate the potential for inducing adverse reactions. However, IgG antivenom had higher anticomplementary activity and induced a stronger anti-immunoglobulin response than F(ab H) 2 antivenom.
The American Journal of Tropical Medicine and Hygiene, 1999
A comparative study was performed on the ability of IgG and F(abЈ) 2 antivenoms to neutralize lethal and myotoxic activities of Micrurus nigrocinctus venom. Both antivenoms were adjusted to a similar neutralizing potency in experiments where venom and antivenoms were preincubated prior to injection. No significant differences were observed between IgG and F(abЈ) 2 antivenoms concerning neutralization of lethal effect in rescue experiments, i.e., when antivenom was administered intravenously after envenomation. However, F(abЈ) 2 antivenom was more effective in prolonging the time of death when subneutralizing doses were administered immediately after venom injection. Both products partially reversed the binding of M. nigrocinctus ␣-neurotoxins to acetylcholine receptor in vitro. The IgG and F(abЈ) 2 antivenoms effectively neutralized venom-induced myotoxicity when administered intravenously immediately after envenomation, although neutralization was poor if antivenom injections were delayed. Intramuscular injection of venom promoted diffusion of antivenom antibodies throughout muscle tissue, and F(abЈ) 2 diffused to a higher extent than IgG molecules. Thus, despite the observation that F(abЈ) 2 antivenom was more effective than IgG antivenom in prolonging the time of death when subneutralizing doses were administered immediately after envenomation, no major differences were observed in antivenom neutralization of lethal and myotoxic effects or in their capacity to reverse neurotoxin binding to the acetylcholine receptor.
Toxicon, 1996
A. Rucavado and B. Lomonte. Neutralization of myonecrosis, hemorrhage, and edema induced by Bothrops asper snake venom by homologous and heterologous pre-existing antibodies in mice. Toxicon, 34, 567-577, 1996.-The ability of pre-existing antibodies to neutralize locally-acting toxins of Bothrops asper snake venom was investigated. Hemorrhage, myonecrosis, and edema were markedly reduced in actively immunized mice, although none of these effects was completely abolished. In mice passively immunized with equine antivenom, hemorrhage was prevented completely, while myonecrosis and edema were partially reduced. Pre-existing antibodies did not modify the early stage ( < 3 hr) of venom-induced edema, but significantly accelerated the normalization of this effect within 24 hr. Passive administration of antivenom either 5 or 120 min before venom injection gave similar results, suggesting that the presence of antibodies in the intravascular compartment may fully neutralize locally acting toxins, in this experimental animal model. Overall, the homologous or heterologous origin of antibodies was not a significant factor influencing their in uit,o neutralizing efficiency against local venom effects. Antibody titrations by enzyme-immunoassay using purified toxins and whole venom indicated that serum from actively-immunized mice had a higher proportion of anti-myotoxin antibodies than equine antivenom. Copyright 0 1996 Elsevier Science Ltd. 567 568 A. RUCAVADO and B. LOMONTE
Journal of Pharmacology and Experimental Therapeutics, 1997
Antivenomous immunotherapy is still used empirically. To improve the efficacy and safety of immunotherapy, we studied the effects of administering antivenom antibodies (F(abЈ) 2 ) on the pharmacokinetics of the Vipera aspis venom in rabbits. Free venom levels were measured by enzyme-linked immunosorbent assay and total concentrations were quantified by measuring the radioactivity of trichloroacetic acid-precipitable radioiodinated venom. The intravenous infusion of 125 mg of antivenom 7 h after intramuscular injection with 700 g⅐kg Ϫ1 of V. aspis venom produced a redistribution of the venom antigens from the extravascular to the vascular space. Moreover, antivenom antibodies were able to neutralize the totality of venom antigens in the vascular space, because no free plasma venom ABBREVIATIONS: AUC, area under the curve; AUMC, area under the mean curve; BSA, bovine serum albumin; ELISA, enzyme-linked immunosorbent assay; HMWP, high molecular weight protein; LMWP, low molecular weight polypeptide; PBS, phosphate buffer saline; TCA, trichloroacetic acid; Vd ss , volume of distribution at steady state.
Basic & Clinical Pharmacology & Toxicology, 2015
The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab 0) 2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab 0) 2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab 0) 2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.