Brief isoflurane administration as a post-exposure treatment for organophosphate poisoning.
Neurotoxicology
; 63: 84-89, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28939237
ABSTRACT
Organophosphate chemical threat agents (OP-CTA) exert toxic effects through cholinergic over-activation. However, after the initial cholinergic phase, the pathophysiology shifts to a non-cholinergic phase which leads to prolonged status epilepticus (SE), irreversible neuronal degeneration and long-term damage to the central nervous system. The efficacy of delayed treatments against OP-CTA is generally low due to the fact that most drugs fail to inhibit the later phase of non-cholinergic activation. Recently, we reported that intranasal brain delivery of obidoxime (OBD) provides complete neuroprotection against a lethal dose of paraoxon when administered 5min after intoxication. In follow-up studies, we examined the window of effectiveness and found that OBD lost effectiveness around 15min post-exposure, which corresponds to the onset of the non-cholinergic phase of intoxication. However, we observed that a brief isoflurane administration, the inhalation anesthetic used to facilitate intranasal drug administration, was effective against paraoxon-induced neurotoxicity. Thus, the present study aimed to investigate the time-course and dose-response efficacy of a brief 4min isoflurane administration as a treatment for neurotoxicity induced by OP-CTA. We found that isoflurane is a potent anti-seizure agent and neuroprotectant when administered between 20 and 30min after paraoxon exposure, stopping SE within 10min of administration and preventing acute neurodegeneration seen 24h later. We also found that the seizure blocking and neuroprotectant properties of isoflurane, when administered 30min after paraoxon, are dose-dependent. The effectiveness and current clinical use of isoflurane support its use as an innovative approach for post exposure treatment of organophosphate poisoning.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anestésicos Inalatórios
/
Intoxicação por Organofosfatos
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Isoflurano
Tipo de estudo:
Etiology_studies
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Observational_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurotoxicology
Ano de publicação:
2017
Tipo de documento:
Article