Neutralization of Bothrops mattogrossensis snake venom from Bolivia: experimental evaluation of llama and donkey antivenoms produced by caprylic acid precipitation.
Abstract: Polyspecific bothropic/crotalic and bothropic/lachesic antivenoms were produced in Bolivia by immunizing two donkeys with the venoms of Bothrops mattogrossensis and Crotalus durissus terrificus and one llama with the venoms of B. mattogrossensis and Lachesis muta. These antivenoms are currently being used for snakebite envenomation in Bolivia. The rationale for using these animals is that donkeys and llamas are better adapted than horses to the high altitudes in South America and constitute good alternatives for antivenom production in these regions. Plasma was fractionated by caprylic acid precipitation of non-immunoglobulin plasma proteins, to obtain whole IgG preparations. Donkey-derived antivenom showed one band of 150 kDa when analyzed by SDS-PAGE, whereas llama antivenom presented two immunoglobulin bands, of 170 kDa and 120 kDa, the latter corresponding to the heavy-chain antibodies present in camelid sera. The effectiveness of these antivenoms to neutralize lethal, hemorrhagic, myotoxic, edema-forming, and defibrinogenating activities of the venom of B. mattogrossensis from Bolivia, a species formerly known as Bothrops neuwiedii, was assessed at the experimental level. Although llama antivenom has a total protein concentration four times lower than donkey antivenom, both preparations have similar neutralizing capacity against all toxic activities assessed. Llama and donkey IgG-based antivenoms are effective in the neutralization of B. mattogrossensis venom and represent valuable alternatives for antivenom manufacture in highland regions of South America.
Copyright 2009 Elsevier Ltd. All rights reserved.
Publication Date: 2009-08-05 PubMed ID: 19647761DOI: 10.1016/j.toxicon.2009.07.031Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article is about the development of effective antivenoms for the venom of Bothrops mattogrossensis snake, using llamas and donkeys for the production of the antivenoms, due to their better acclimatization to high altitudes in South America.
Production of Antivenoms
- The researchers produced antivenoms by immunizing two donkeys with the venom of Bothrops mattogrossensis and Crotalus durissus terrificus snakes. Additionally, they also immunized a llama with venoms from B. mattogrossensis and Lachesis muta snake.
- The use of donkeys and llamas as a source for immunizing venom was based on the assumption that these animals are better adapted to the high altitudes of South America, making them favourable choices for antivenom production in these regions.
- The plasma from these animals was then divided by means of caprylic acid precipitation, a method used to segregate non-immunoglobulin plasma proteins, which in turn aided in procuring IgG preparations in whole.
Analysis of Antivenoms
- The produced antivenoms were examined by SDS-PAGE, a common lab technique for the separation of proteins. The donkey-derived antivenom showed a single band of 150 kDa whereas the llama’s antivenom displayed two immunoglobulin bands, 170 kDa and 120 kDa, with the latter believed to belong to the heavy-chain antibodies found in camelid sera.
Effectiveness of Antivenoms
- The antivenoms’ ability to neutralize the lethal effects of the venom of B. mattogrossensis was tested on a lab-scale. The toxic activities that were measured include causing death, uncontrolled bleeding (hemorrhagic), muscle injury (myotoxic), occurrence of swelling and inflammation (edema-forming) and blood clotting (defibrinogenating).
- Although the llama antivenom had a total protein concentration four times lower than the donkey antivenom, the efficacy to neutralize the toxic effects was similar for both.
- The antivenoms made from IgG derived from both llama and donkey were found to be effective in neutralizing B. mattogrossensis venom, therefore providing a valuable alternative for antivenom production in the highland regions of South America.
Cite This Article
APA
Fernández GP, Segura A, Herrera M, Velasco W, Solano G, Gutiérrez JM, León G.
(2009).
Neutralization of Bothrops mattogrossensis snake venom from Bolivia: experimental evaluation of llama and donkey antivenoms produced by caprylic acid precipitation.
Toxicon, 55(2-3), 642-645.
https://doi.org/10.1016/j.toxicon.2009.07.031 Publication
Researcher Affiliations
- Laboratorio de Producción de Antiveninas, Instituto Nacional de Laboratorios de Salud, La Paz, Bolivia.
MeSH Terms
- Animals
- Antivenins / biosynthesis
- Antivenins / chemistry
- Antivenins / pharmacology
- Bolivia
- Bothrops / physiology
- Camelids, New World / immunology
- Caprylates / chemistry
- Edema / chemically induced
- Edema / prevention & control
- Electrophoresis, Polyacrylamide Gel
- Equidae / immunology
- Fibrinogen / antagonists & inhibitors
- Hemorrhage / blood
- Hemorrhage / chemically induced
- Hemorrhage / prevention & control
- Mice
- Muscular Diseases / chemically induced
- Muscular Diseases / prevention & control
- Viper Venoms / antagonists & inhibitors
Citations
This article has been cited 9 times.- Zhang J, Cui D, Zuo Y, Zheng Z, Wu F, Li W, Zhang Y, Huo S, Li N, Li L, Guan Y, Zhong F. Donkey-derived anti-CDV IgG, as a passive immunotherapy agent, can effectively increase survival rates of the experimental CDV-infected dogs. BMC Vet Res 2021 Aug 6;17(1):266.
- Di Fabio JL, Cortés Castillo MLÁ, Griffiths E. Landscape of research, production, and regulation in venoms and antivenoms: a bibliometric analysis. Rev Panam Salud Publica 2021;45:e55.
- Salvador GHM, Gomes AAS, Bryan-Quirós W, Fernández J, Lewin MR, Gutiérrez JM, Lomonte B, Fontes MRM. Structural basis for phospholipase A(2)-like toxin inhibition by the synthetic compound Varespladib (LY315920). Sci Rep 2019 Nov 20;9(1):17203.
- de Moura AA, Kayano AM, Oliveira GA, Setúbal SS, Ribeiro JG, Barros NB, Nicolete R, Moura LA, Fuly AL, Nomizo A, da Silva SL, Fernandes CF, Zuliani JP, Stábeli RG, Soares AM, Calderon LA. Purification and biochemical characterization of three myotoxins from Bothrops mattogrossensis snake venom with toxicity against Leishmania and tumor cells. Biomed Res Int 2014;2014:195356.
- Khamehchian S, Zolfagharian H, Dounighi NM, Tebianian M, Madani R. Study on camel IgG purification: a new approach to prepare Naja Naja Oxiana antivenom as passive immunization for therapy. Hum Vaccin Immunother 2014;10(6):1633-8.
- Richard G, Meyers AJ, McLean MD, Arbabi-Ghahroudi M, MacKenzie R, Hall JC. In vivo neutralization of α-cobratoxin with high-affinity llama single-domain antibodies (VHHs) and a VHH-Fc antibody. PLoS One 2013;8(7):e69495.
- Sánchez A, Cerdas M, Gutiérrez J, Vargas M, Segura Á, Herrera M, Chaves-Araya S, Sánchez R, Villalta M, Durán G, Sánchez A, Solano G, Cordero D, Sánchez P, Gutiérrez JM, León G. Pilot-scale evaluation of a dynamic body-feed filtration system for primary clarification of snake antivenoms produced by the caprylic acid method. Toxicon X 2024 Sep;23:100202.
- Wang W-C, Chang J, Lee C-H, Chiang Y-W, Leu S-J, Mao Y-C, Chiang J-R, Yang C-K, Wu C-J, Yang Y-Y. Phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation. Appl Environ Microbiol 2024 Aug 21;90(8):e0012124.
- Gamulin E, Mateljak Lukačević S, Halassy B, Kurtović T. Snake Antivenoms-Toward Better Understanding of the Administration Route. Toxins (Basel) 2023 Jun 15;15(6).
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