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dc.creatorAntonijević, Evica
dc.creatorMusilek, Kamil
dc.creatorKuca, Kamil
dc.creatorĐukić-Ćosić, Danijela
dc.creatorVučinić, Slavica
dc.creatorAntonijević, Biljana
dc.date.accessioned2019-09-02T11:53:43Z
dc.date.available2019-09-02T11:53:43Z
dc.date.issued2016
dc.identifier.issn0161-813X
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/2655
dc.description.abstractAs oxime-based structures are the only causal antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE), the majority of studies on these have been directed towards their synthesis and testing. In this study, experimental bispyridinium oximes K027 and K203, which have shown promising results in the last decade of research, were examined in vivo for their therapeutic and reactivating ability in acute poisoning by the direct AChE-inhibitor dichlorvos (DDVP), used as a dimethyl OP structural model. Additionally, the efficacy of oximes K027 and K203 was compared with the efficacy of four oximes (pralidoxime, trimedoxime, obidoxime and HI-6), already used in efficacy experiments and human medicine. To evaluate therapeutic efficacy, groups of Wistar rats were treated with equitoxic doses of oximes (5% LD50, i.m.) and/or atropine (10 mg/kg, i.m.) immediately after s.c. DDVP challenge (4-6 doses). Using the same antidotal protocol, AChE activity was measured in erythrocytes, diaphragm and brain 60 min after s.c. DDVP exposure (75% LD50). The oxime K027 was the most efficacious in reducing the DDVP induced lethal effect in rats, while the oxime K203 was more efficacious than trimedoxime, pralidoxime and HI-6. Significant reactivation of DDVP inhibited AChE was achieved only with oxime K027 or its combination with atropine in erythocytes and the diaphragm. Moreover, the acute i.m. toxicity of oxime K027 in rats was lower than all other tested oximes. The results of this study support previous studies considering the oxime K027 as a promising experimental oxime structure for further testing against structurally-different OP compounds.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/46009/RS//
dc.relationAgency of the Czech Republic - GA15-16701S
dc.relationUniversity of Hradec Kralove (Faculty of Science) - SV2110/2016
dc.rightsrestrictedAccess
dc.sourceNeurotoxicology
dc.titleTherapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitoren
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМусилек, Камил; Ђукић-Ћосић, Данијела; Aнтонијевић, Евица; Aнтонијевић, Биљана; Куца, Камил; Вучинић, Славица;
dc.citation.volume55
dc.citation.spage33
dc.citation.epage39
dc.citation.other55: 33-39
dc.citation.rankM22
dc.identifier.wos000380385800005
dc.identifier.doi10.1016/j.neuro.2016.05.006
dc.identifier.pmid27177985
dc.identifier.scopus2-s2.0-84969560264
dc.type.versionpublishedVersion


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