Immunoglobulin G and F(ab′) 2 polyvalent antivenoms do not differ in their ability to neutralize hemorrhage, edema and myonecrosis induced by Bothrops asper (terciopelo) snake venom (original) (raw)
Toxicon, 2013
Snake antivenoms are formulations of immunoglobulins, or immunoglobulin fragments, purified from the plasma of animals immunized with snake venoms. Their therapeutic success lies in their ability to mitigate the progress of toxic effects induced by snake venom components, when administered intravenously. However, due to diverse factors, such as deficient manufacturing practices, physicochemical characteristics of formulations, or inherent properties of heterologous immunoglobulins, antivenoms can induce undesirable adverse reactions. Based on the time lapse between antivenom administration and the onset of clinical manifestations, the World Health Organization has classified these adverse reactions as: 1 -Early reactions, if they occur within the first hours after antivenom infusion, or 2late reactions, when occurring between 5 and 20 days after treatment. While all late reactions are mediated by IgM or IgG antibodies raised in the patient against antivenom proteins, and the consequent formation of immune complexes, several mechanisms may be responsible for the early reactions, such as pyrogenic reactions, IgEmediated reactions, or non IgE-mediated reactions. This work reviews the hypotheses that have been proposed to explain the mechanisms involved in these adverse reactions to antivenoms. The understanding of these pathogenic mechanisms is necessary for the development of safer products and for the improvement of snakebite envenomation treatment.
Cross reactivity of three antivenoms against North American snake venoms
Toxicon, 2003
The antivenom in the United States today is in short supply, expensive and may not even be the most effective in neutralizing venoms from snakes in certain geographical locations. The ED 50 is considered to be the best indicator of antivenom efficacy, however, other tests are needed. In this study, three antivenoms (Antivipmyn (Fab 2 H), Crotalidae Polyvalent Immune Fab (Ovine) (FabO) and UCV (FabV) were used to test the effectiveness of neutralization of eight venoms (Agkistrodon piscivorus piscivorus, Bothrops asper, Crotalus adamanteus, C. durissus durissus, C. horridus atricaudatus, C. h. horridus, C. atrox, and C. molossus molossus). Four different assays were used to study the efficacy of the antivenoms: the antihemorrhagic, antigelatinase, antifibrinolytic and antihide powder azure. Fab 2 H antivenom was more effective in neutralizing the enzymatic activities of these eight venoms than FabO and FabV antivenoms.
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.
Toxicon, 2007
Despite preventing death after snakebites, there is little evidence that polyvalent antivenoms (PAVs) protect against myotoxicity and local damages. We evaluated antibothropic Brazilian PAVs from three manufacturers against the myotoxicity and hemorrhagic activity of Bothrops jararacussu and B. jararaca venoms, respectively, by using two protocols: preincubation of PAVs with venom, and i.v. pretreatment with PAVs, prior to the venom inoculation. In this investigation, we used doses of PAVs ranging from 0.4 to 4.0 mL/mg of venom equivalent up to 10 times the amount recommended by the producers for the clinical practice in Brazil. In our preincubation protocol in vivo, PAVs antagonized myotoxicity of B. jararacussu venom by 40–95%, while our pretreatment protocol antagonized myotoxic activity by 0–60%. Preincubation of antivenoms with B. jararaca venom antagonized its hemorrhagic activity by 70–95%, while pretreatment antagonized hemorrhagic activity by 10–50%. Although all PAVs demonstrated partial antagonism against both venoms, the magnitude of these effects varied greatly among the manufactures. The results suggest that the current clinical doses of these PAVs may have negligible antimyotoxic effect.
Pro-inflammatory activities in elapid snake venoms
British Journal of Pharmacology, 1994
1 Snake venoms from the genera Micrurus (M. ibiboboca and M. spixii) and Naja (N. naja, N. melanoleuca and N. nigricollis) were analysed, using biological and immunochemical methods, to detect pro-inflammatory activities, cobra venom factor (COF), proteolytic enzymes, thrombin-like substances, haemorrhagic and oedema-producing substances. 2 The venoms of the five snake species activate the complement system (C) in normal human serum (NHS) in a dose-related fashion, at concentrations ranging from 5 jig to 200 pg ml-' serum. Electrophoretic conversion of C3 was observed with all venoms in NHS containing normal concentrations of Ca2+ and Mg2", but only by venoms from N. naja and N. melanoleuca when Ca2+ was chelated by adding Mg2+-EGTA. 3 Purified human C3 was electrophoretically converted, in the absence of other C components, by the venoms from N. naja, N. nigricollis and M. ibiboboca. However, only the venoms from N. naja and N. melanoleuca contained a 144 kDa protein revealed in Western blot with sera against COF or human C3. 4 All venoms, at minimum concentrations of 30 ng ml-', were capable of lysing sheep red blood cells, also in a dose-related fashion, when incubated with these cells in presence of egg yolk as a source of lecithin. Although the venoms from M. spixii and N. nigricollis showed detectable thrombin-like activity, these and the other venoms were free of proteolytic activity when fibrin, gelatin and casein, were used as substrates. 5 When tested on mice skin, all five venoms were capable of inducing an increase in vascular permeability and oedema, but were devoid of haemorrhagic producing substances (haemorrhagins). 6 These data provide evidence indicating that Elapidae venoms contain various pro-inflammatory factors which may be important in the spreading of neurotoxins throughout the tissues of the prey or human victim.
Molecular Immunology, 2010
Snake venoms are a complex mixture of components, which have a wide range of actions both on prey and human victims. The genus Bothrops causes the vast majority of snakebites in Central and South America, being responsible for 80% of snake envenomations in Brazil. Envenomations are characterized by prominent local effects, including oedema, haemorrhage and necrosis, which can lead to permanent disability. Systemic manifestations such as haemorrhage, coagulopathy, shock and acute renal failure may also occur.
Antibodies as Snakebite Antivenoms: Past and Future
Toxins
Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab’)2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It i...