Inhibition by CaNa2EDTA of local tissue damage induced by Bothrops asper (terciopelo) venom: application in horse immunization for antivenom production.
Abstract: The ability of the chelating agent CaNa2EDTA to inhibit local tissue damage induced by Bothrops asper venom was studied in mice and in horses used for polyvalent (Crotalinae) antivenom production. CaNa2EDTA was devoid of toxicity when injected i.m. or s.c. inducing only a mild edema. Preincubation of B. asper venom with CaNa2EDTA inhibited hemorrhagic and dermonecrotic activities, but did not reduce edema-forming and myotoxic effects. A group of horses initially immunized with native venoms developed less severe local tissue reactions when injected with booster doses of venom and CaNa2EDTA than when receiving booster injections of venom alone, although they showed a similar antivenom response. Moreover, antivenoms produced from plasmas of horses that received booster injections of either venom alone or venom plus CaNa2EDTA had similar neutralizing activity against lethal, hemorrhagic and coagulant effects induced by B. asper venom. The similar antibody response was corroborated by Western blotting using crude venom and by an ELISA that estimates anti-myotoxin titer. It is concluded that the chelating agent CaNa2EDTA reduces the extent of local tissue damage induced by B. asper venom, without affecting the immune response of horses against pharmacologically-relevant venom components.
Publication Date: 1998-06-10 PubMed ID: 9620579DOI: 10.1016/s0041-0101(97)00114-1Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research explores the use of a chelating agent, CaNa2EDTA, for reducing the tissue damage induced by Bothrops asper venom in mice and horses. The findings suggest that this agent can decrease the venom’s harmful effects without impacting the immune response in horses, which is beneficial for the production of antivenom.
Overview of the Research
- The study aims to observe the capacity of the chelating agent CaNa2EDTA to inhibit the tissue damage caused by Bothrops asper, also known as terciopelo, venom in mice and horses.
- Bothrops asper venom is potent and can cause severe local tissue damage. This research looks at ways to minimize that damage, especially in horses used for polyvalent (Crotalinae) antivenom production.
Methodology and Findings
- The researchers found that CaNa2EDTA injected into the muscles or skin of mice caused only mild edema, making it non-toxic.
- It significantly lessened the hemorrhagic and dermonecrotic actions (bleeding and skin tissue death, respectively) of the venom. However, it did not reduce the venom’s edema-forming and myotoxic effects, which cause swelling and muscle damage.
- A group of horses was initially immunized with native venoms and then given a booster with venom and CaNa2EDTA. This group exhibited less severe local tissue reactions than a group treated with a booster of venom alone. Importantly, both groups had a similar immune or antivenom response.
Impact on Antivenom Production
- The antivenoms produced from the plasma of horses that received the venom and CaNa2EDTA boosters, and those that received venom alone, were equally effective against the lethal, hemorrhagic and coagulant effects of B. asper venom.
- Western blotting and ELISA tests that measure anti-myotoxin titer confirmed the similarity of the antibody response. The two tests provided corroborating results, confirming that adding CaNa2EDTA doesn’t affect the immune response of horses to the venom.
Conclusion
- The study concluded that using the chelating agent CaNa2EDTA lessens local tissue damage inflicted by Bothrops asper venom.
- Despite reducing venom-induced tissue damage, it does not hinder the immune response of horses against essential venom components. This outcome suggests that CaNa2EDTA usage could improve the process and outcomes of antivenom production in horses.
Cite This Article
APA
León G, Estrada R, Chaves F, Rojas G, Ovadia M, Gutiérrez JM.
(1998).
Inhibition by CaNa2EDTA of local tissue damage induced by Bothrops asper (terciopelo) venom: application in horse immunization for antivenom production.
Toxicon, 36(2), 321-331.
https://doi.org/10.1016/s0041-0101(97)00114-1 Publication
Researcher Affiliations
- Facultad de Microbiología, Instituto Clodomiro Picado, Universidad de Costa Rica, San José.
MeSH Terms
- Animals
- Antivenins / biosynthesis
- Bothrops
- Chelating Agents / administration & dosage
- Chelating Agents / therapeutic use
- Crotalid Venoms / antagonists & inhibitors
- Crotalid Venoms / toxicity
- Dose-Response Relationship, Drug
- Edetic Acid / administration & dosage
- Edetic Acid / therapeutic use
- Hemorrhage / drug therapy
- Horses / immunology
- Injections, Intramuscular
- Injections, Intraperitoneal
- Mice
- Necrosis
- Neutralization Tests
Citations
This article has been cited 5 times.- Werner RM, Soffa AN. Considerations for the development of a field-based medical device for the administration of adjunctive therapies for snakebite envenoming.. Toxicon X 2023 Dec;20:100169.
- Huertas RM, Arguedas M, Estrada JM, Moscoso E, Umaña D, Solano G, Vargas M, Segura Á, Sánchez A, Herrera M, Villalta M, Arroyo-Portilla C, Gutiérrez JM, León G. Clinical effects of immunization, bleeding, and albumin-based fluid therapy in horses used as immunoglobulin source to produce a polyspecific antivenom (Echitab-plus-ICP) towards venoms of African snakes.. Toxicon X 2023 Jun;18:100158.
- Gómez A, Sánchez A, Durán G, Cordero D, Segura Á, Vargas M, Solano D, Herrera M, Chaves-Araya S, Villalta M, Sánchez M, Arguedas M, Díaz C, Gutiérrez JM, León G. Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of the medically most important Bitis spp. and Echis spp. African snakes.. PLoS Negl Trop Dis 2022 Aug;16(8):e0010643.
- Ratanabanangkoon K. A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms.. Front Immunol 2021;12:668328.
- Guimarães CL, Andrião-Escarso SH, Moreira-Dill LS, Carvalho BM, Marchi-Salvador DP, Santos-Filho NA, Fernandes CA, Fontes MR, Giglio JR, Barraviera B, Zuliani JP, Fernandes CF, Calderón LA, Stábeli RG, Albericio F, da Silva SL, Soares AM. Alkylation of histidine residues of Bothrops jararacussu venom proteins and isolated phospholipases A2: a biotechnological tool to improve the production of antibodies.. Biomed Res Int 2014;2014:981923.
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