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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gina Durán, Gabriela Solano, Aarón Gómez, Daniel Cordero, Adriana Sánchez, Mauren Villalta, Melvin Sánchez, Cecilia Díaz, José María Gutiérrez, Guillermo León
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Antivenom potency Lethality neutralization assay Median effective dose Median lethal dose Replacement Reduction Toxicology. Poisons RA1190-1270
Acceso en línea:	https://doaj.org/article/1f4afb236e95440e81a6549442e93159
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1f4afb236e95440e81a6549442e93159
record_format	dspace
spelling	oai:doaj.org-article:1f4afb236e95440e81a6549442e931592021-11-28T04:37:58ZAssessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms2590-171010.1016/j.toxcx.2021.100087https://doaj.org/article/1f4afb236e95440e81a6549442e931592021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590171021000230https://doaj.org/toc/2590-1710The 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.Gina DuránGabriela SolanoAarón GómezDaniel CorderoAdriana SánchezMauren VillaltaMelvin SánchezCecilia DíazJosé María GutiérrezGuillermo LeónElsevierarticleAntivenom potencyLethality neutralization assayMedian effective doseMedian lethal doseReplacementReductionToxicology. PoisonsRA1190-1270ENToxicon: X, Vol 12, Iss , Pp 100087- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Antivenom potency Lethality neutralization assay Median effective dose Median lethal dose Replacement Reduction Toxicology. Poisons RA1190-1270
spellingShingle	Antivenom potency Lethality neutralization assay Median effective dose Median lethal dose Replacement Reduction Toxicology. Poisons RA1190-1270 Gina Durán Gabriela Solano Aarón Gómez Daniel Cordero Adriana Sánchez Mauren Villalta Melvin Sánchez Cecilia Díaz José María Gutiérrez Guillermo León Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
description	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.
format	article
author	Gina Durán Gabriela Solano Aarón Gómez Daniel Cordero Adriana Sánchez Mauren Villalta Melvin Sánchez Cecilia Díaz José María Gutiérrez Guillermo León
author_facet	Gina Durán Gabriela Solano Aarón Gómez Daniel Cordero Adriana Sánchez Mauren Villalta Melvin Sánchez Cecilia Díaz José María Gutiérrez Guillermo León
author_sort	Gina Durán
title	Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
title_short	Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
title_full	Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
title_fullStr	Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
title_full_unstemmed	Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
title_sort	assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1f4afb236e95440e81a6549442e93159
work_keys_str_mv	AT ginaduran assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT gabrielasolano assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT aarongomez assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT danielcordero assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT adrianasanchez assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT maurenvillalta assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT melvinsanchez assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT ceciliadiaz assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT josemariagutierrez assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms AT guillermoleon assessinga6hendpointobservationtimeinthelethalityneutralizationassayusedtoevaluatethepreclinicalefficacyofsnakeantivenoms
_version_	1718408246068248576

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

Ejemplares similares