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Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms

artículo científico
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Date
2021-11
Author
Durán Blanco, Gina
Solano Blanco, María Gabriela
Gómez Argüello, Aarón
Cordero Vásquez, Daniel
Sánchez Sánchez, Adriana
Villalta Arrieta, Mauren
Sánchez Chaves, Melvin
Díaz Oreiro, Cecilia
Gutiérrez, José María
León Montero, Guillermo
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Abstract
The lethality neutralization assay in mice is the gold standard for the evaluation of the preclinical efficacy and specification fulfillment of snake antivenoms. However, owing to the animal suffering involved, this assay is a candidate to be replaced by in vitro alternatives or, at least, improved by the reduction of the number of animals used per experiment, the introduction of analgesia, and the refinement of the test. Since these tests are usually run for 24 or 48 h, one possibility to refine it is to shorten the endpoint observation time of the assay and so limiting the duration of suffering. To assess the effect of this modification of the standard procedure on the analytical properties of the assay, we compared the median lethal dose (LD50) and median effective dose (ED50) values, estimated through observation times of 6, 24 and 48 h. We used African and Latin American snake venoms and several batches of two polyspecific antivenoms. A significant correlation was found between LD50 and ED50 values estimated at the three observation times. Although some LD50 and ED50 values were significantly different at these time points, results of 6 h were robust enough to be used in the characterization of new antivenoms, the verification of specification compliance, and the parallel comparison of formulations. Our observations support the modification of the standard procedures used for assessing neutralizing ability of antivenoms by carrying out the observations at 6 h instead of 24 or 48 h, with the consequent reduction in the suffering inflicted upon mice during these assays. However, the shortening of the observation time in the lethality tests must be validated for each venom and antivenom before its introduction in the routine procedures.
URI
https://hdl.handle.net/10669/86545
External link to the item
10.1016/j.toxcx.2021.100087
www.sciencedirect.com/science/article/pii/S2590171021000230
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  • Repositorios universitarios

  • Repositorio del SIBDI-UCR
  • Biblioteca Digital del CIICLA
  • Repositorio Documental Rafael Obregón Loría (CIHAC)
  • Biblioteca Digital Carlos Melendez (CIHAC)
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  • Colección de videos de UPA-VAS
  • Sitios recomendados

  • Buscador regional de LA Referencia
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  • Scientific Electronic Library Online (SciELO)
  • Directory of Open Access Journals (DOAJ)
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Repositorio Institucional de la Universidad de Costa Rica. Algunos derechos reservados. Este repositorio funciona con DSpace.