In vitro detoxification of cyclosarin (GF) by modified cyclodextrins. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Toxicology Letters Année : 2011

In vitro detoxification of cyclosarin (GF) by modified cyclodextrins.

Résumé

Developing potent detoxification strategies for prophylaxis and therapy against organophosphate (OP) intoxication still represents a challenging task. Clinical application of numerous investigated substances including enzymes and low molecular scavengers like metal ions or nucleophiles could not yet be realised due to profound disadvantages. Presenting a promising attempt, cyclodextrins (CDs) efficiently enhance the degradation of some organophosphorus compounds. The present study examined the in vitro GF degradation mediated by three CDs and a nucleophilic precursor performed by mass spectrometric detection with ammonia chemical ionisation. All four compounds caused a notable enhancement of GF detoxification that was synergistically accelerated in the case of 2-O-(3-carboxy-4-iodosobenzyl)-β-cyclodextrin (IBA-β-CD) with the alpha-nucleophile 2-iodosobenzoic acid (IBA) grafted on the secondary face of β-cyclodextrin (β-CD). In vitro toxicokinetic investigations of CD derivatives are needed to evaluate the effect of slow terminal elimination phase of the more toxic (-)-GF shown for two CD-derivatives underlining the necessity of detecting the complete kinetic course of inactivation. The observed effect of fast high affinity binding (20-30%) represents an additional therapeutic option of an extremely rapid reduction of GF concentration in vivo. Distinctive differences in the course of reaction are detected depending on β-CD-derivatives, allowing a first inference of possible mechanisms and relevance of attached substituents. However, further profound investigation needs to be done to evaluate the basis of a clinical application of substituted CDs as potential detoxification agents.

Domaines

Chimie organique

Dates et versions

hal-00992063 , version 1 (16-05-2014)

Identifiants

Citer

Susanne Müller, Marianne Koller, Romain Le Provost, Olivier Lafont, François Estour, et al.. In vitro detoxification of cyclosarin (GF) by modified cyclodextrins.. Toxicology Letters, 2011, 200 (1-2), pp.53-58. ⟨10.1016/j.toxlet.2010.10.014⟩. ⟨hal-00992063⟩
26 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More