An Antidote Screening System for Organophosphorus Poisoning Using Zebrafish Larvae.
ACS Chem Neurosci
; 12(15): 2865-2877, 2021 08 04.
Article
en En
| MEDLINE
| ID: mdl-34284583
ABSTRACT
Organophosphorus (OP) cholinesterase inhibitors, which include insecticides and chemical warfare nerve agents, are very potent neurotoxicants. Given that the actual treatment has several limitations, the present study provides a general method, called the zebrafish-OP-antidote test (ZOAT), and basic scientific data, to identify new antidotes that are more effective than the reference pyridinium oximes after acute OP poisoning. The reactivation capacity of a chemical compound can be measured using in vivo and ex vivo acetylcholinesterase (AChE) assays. We demonstrated that it is possible to differentiate between chemical compound protective efficacies in the central and peripheral nervous system via the visual motor response and electric field pulse motor response tests, respectively. Moreover, the ability to cross the brain-blood barrier can be estimated in a physiological context by combining an AChE assay on the head and trunk-tail fractions and the cellular and tissue localization of AChE activity in the whole-mount animal. ZOAT is an innovative method suitable for the screening and rapid identification of chemicals and mixtures used as antidote for OP poisoning. The method will make it easier to identify more effective medical countermeasures for chemical threat agents, including combinatorial therapies.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Reactivadores de la Colinesterasa
/
Intoxicación por Organofosfatos
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article