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dc.creatorAntonijević, Evica
dc.creatorMusilek, Kamil
dc.creatorKuca, Kamil
dc.creatorĐukić-Ćosić, Danijela
dc.creatorĆurčić, Marijana
dc.creatorČupić-Miladinović, Dejana
dc.creatorBulat, Zorica
dc.creatorAntonijević, Biljana
dc.date.accessioned2019-09-02T12:03:39Z
dc.date.available2019-09-02T12:03:39Z
dc.date.issued2018
dc.identifier.issn0278-6915
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3055
dc.description.abstractInhibition of acethylcholinesterase (AChE) as a key molecular event induced by organophosphate (OP) pesticides and nerve agents presents a human health concern. In efficacy testing of experimental oximes, potential antidotes in OP poisoning, reactivation of OP-inhibited AChE is used as specific endpoint. However, according to our best knowledge, so far oximes have not been quantitatively evaluated by comprehensive benchmark dose (BMD) approach, that would improve both identification and quantification of the effect and allow more rigorous comparison of efficacies. Thus, we have examined in vivo dose-response relationship for two promising experimental oximes, K203 and K027, concerning reactivation of erythrocyte AChE inhibited by dichlorvos (DDVP). Groups of Wistar rats were treated with six different doses of oximes (i.m) immediately after DDVP challenge (s.c) and AChE was measured 60 min later. Dose-response modeling was done by PROAST software 65.5 (RIVM, The Nederlands). BMD-covariate method resulted in four-parameter model from both exponential and Hill model families as the best estimate of relationship between AChE activity and oxime dose, with potency parameter being oxime-dependent. Oxime K027 was shown to be 1.929-fold more potent considering that 58% increase in AChE activity was achived with the dose BMD58-K027 = 52 mu mol/kg in contrast to BMD58-K203 = 100 mu mol/kg.en
dc.publisherPergamon-Elsevier Science Ltd, Oxford
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/46009/RS//
dc.rightsrestrictedAccess
dc.sourceFood and Chemical Toxicology
dc.subjectDichlorvosen
dc.subjectK027 vs K203en
dc.subjectRat erythrocytesen
dc.subjectBenchmark doseen
dc.subjectPROASTen
dc.titleDose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЧупић-Миладиновић, Дејана; Мусилек, Камил; Ћурчић, Маријана; Куца, Камил; Булат, Зорица; Ђукић-Ћосић, Данијела; Aнтонијевић, Евица; Aнтонијевић, Биљана;
dc.citation.volume121
dc.citation.spage224
dc.citation.epage230
dc.citation.other121: 224-230
dc.citation.rankM21
dc.identifier.wos000449242800023
dc.identifier.doi10.1016/j.fct.2018.08.065
dc.identifier.pmid30176309
dc.identifier.scopus2-s2.0-85052992924
dc.identifier.rcubconv_4251
dc.type.versionpublishedVersion


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