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)
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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. #
Experimental pathophysiology of systemic alterations induced by Bothrops asper snake venom
Toxicon, 2009
Moderate and severe envenomations by the snake Bothrops asper provoke systemic alterations, such as systemic bleeding, coagulopathy, hypovolemia, hemodynamic instability and shock, and acute renal failure. Systemic hemorrhage is a typical finding of these envenomations, and is primarily caused by the action of P-III snake venom metalloproteinases (SVMPs). This venom also contains a thrombin-like serine proteinase and a prothrombin-activating P-III SVMP, both of which cause defibrin(ogen)ation. Thrombocytopenia, predominantly induced by a C-type lectin-like protein, and platelet hypoaggregation, caused by the two defibrin(ogen)ating enzymes, also contribute to hemostatic disturbances, which potentiate the systemic bleeding induced by hemorrhagic SVMPs. Cardiovascular disturbances leading to shock are due to the combined effects of hemorrhagic toxins, other venom components that increase vascular permeability, the action of hypotensive agents in the venom and of endogenous mediators, and the potential cardiotoxic effect of some toxins. Renal alterations are likely to be caused by direct cytotoxicity of venom components in the kidney, and by renal ischemia resultant from hypovolemia and hypoperfusion. Lethality induced by B. asper venom is the consequence of several combined effects among which the action of P-III SVMPs is especially relevant.
Tissue damage and inflammation induced by snake venoms
Some characteristics of the local tissue damage and inflammatory reactions induced by snake venoms were analyzed in a mouse model. Tissue damage was studied by intravital, light, and electron microscopic techniques, and by the use of biochemical markers. Detailed information on the early development and dynamics of local tissue damage was obtained by intravital microscopy. Main alterations were microvascular plasma leakage, hemorrhage, blood flow disturbances, thrombosis, and myonecrosis. A new technique for the quantification of myonecrosis in vivo was established, based on the principle of MTT reduction. The method was tested for its usefulness in the evaluation of antibody-mediated neutralization of myotoxicity.
Snake antivenoms: adverse reactions and production technology
Journal of Venomous Animals and Toxins including Tropical Diseases, 2009
Antivenoms have been widely used for more than a century for treating snakebites and other accidents with poisonous animals. Despite their efficacy, the use of heterologous antivenoms involves the possibility of adverse reactions due to activation of the immune system. In this paper, alternatives for antivenom production already in use were evaluated in light of their ability to minimize the occurrence of adverse reactions. These effects were classified according to their molecular mechanism as: anaphylactic reactions mediated by IgE, anaphylactoid reactions caused by complement system activation, and pyrogenic reactions produced mainly by the presence of endotoxins in the final product. In the future, antivenoms may be replaced by humanized antibodies, specific neutralizing compounds or vaccination. Meanwhile, improvements in antivenom quality will be focused on the obtainment of a more purified and specific product in compliance with good manufacturing practices and at an affordable cost.
Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology
Journal of Translational Autoimmunity, 2021
Snake venoms have components with diverse biological actions that are extensively studied to identify elements that may be useful in biomedical sciences. In the field of autoimmunity and rheumatology, various findings useful for the study of diseases and potential drug development have been reported. The study of disintegrins, proteins that block the action of integrins, has been useful for the development of antiplatelet agents and principles for the development of immunosuppressants and antineoplastics. Several proteins in snake venoms act on the coagulation cascade, activating factors that have allowed the development of tests for the study of coagulation, including Russell's viper venom time, which is useful in the diagnosis of antiphospholipid syndrome. Neurotoxins with either pre-or postsynaptic effects have been used to study neurogenic synapses and neuromuscular plaques and the development of analgesics, muscle relaxants and drugs for neurodegenerative diseases. Various components act by inhibiting cells and proteins of the immune system, which will allow the development of anti-inflammatory and immunosuppressive drugs. This review summarizes the usefulness of the components of snake venoms in the fields of autoimmunity and rheumatology, which can serve as a basis for diverse translational research.
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.