TY  - JOUR
AU  - Antonijević, Evica
AU  - Musilek, Kamil
AU  - Kuca, Kamil
AU  - Đukić-Ćosić, Danijela
AU  - Curcić, Marijana
AU  - Ćupić Miladinović, Dejana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
PY  - 2018
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1566
AB  - Inhibition 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.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Food and Chemical Toxicology
T1  - Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes
VL  - 121
SP  - 224
EP  - 230
DO  - 10.1016/j.fct.2018.08.065
ER  - 

@article{
author = "Antonijević, Evica and Musilek, Kamil and Kuca, Kamil and Đukić-Ćosić, Danijela and Curcić, Marijana and Ćupić Miladinović, Dejana and Bulat, Zorica and Antonijević, Biljana",
year = "2018",
abstract = "Inhibition 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.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Food and Chemical Toxicology",
title = "Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes",
volume = "121",
pages = "224-230",
doi = "10.1016/j.fct.2018.08.065"
}

Antonijević, E., Musilek, K., Kuca, K., Đukić-Ćosić, D., Curcić, M., Ćupić Miladinović, D., Bulat, Z.,& Antonijević, B.. (2018). Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes. in Food and Chemical Toxicology
Pergamon-Elsevier Science Ltd, Oxford., 121, 224-230.
https://doi.org/10.1016/j.fct.2018.08.065

Antonijević E, Musilek K, Kuca K, Đukić-Ćosić D, Curcić M, Ćupić Miladinović D, Bulat Z, Antonijević B. Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes. in Food and Chemical Toxicology. 2018;121:224-230.
doi:10.1016/j.fct.2018.08.065 .

Antonijević, Evica, Musilek, Kamil, Kuca, Kamil, Đukić-Ćosić, Danijela, Curcić, Marijana, Ćupić Miladinović, Dejana, Bulat, Zorica, Antonijević, Biljana, "Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes" in Food and Chemical Toxicology, 121 (2018):224-230,
https://doi.org/10.1016/j.fct.2018.08.065 . .