کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599941 1133242 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro detoxification of cyclosarin in human blood pre-incubated ex vivo with recombinant serum paraoxonases
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
In vitro detoxification of cyclosarin in human blood pre-incubated ex vivo with recombinant serum paraoxonases
چکیده انگلیسی

An ex vivo protocol was developed to assay the antidotal capacity of rePON1 variants to protect endogenous acetylcholinesterase and butyrylcholinesterase in human whole blood against OP nerve agents. This protocol permitted us to address the relationship between blood rePON1 concentrations, their kinetic parameters, and the level of protection conferred by rePON1 on the cholinesterases in human blood, following a challenge with cyclosarin (GF). The experimental data thus obtained were in good agreement with the predicted percent residual activities of blood cholinesterases calculated on the basis of the rate constants for inhibition of human acetylcholinesterase and butyrylcholinesterase by GF, the concentration of the particular rePON1 variant, and its kcat/Km value for GF. This protocol thus provides a rapid and reliable ex vivo screening tool for identification of rePON1 bioscavenger candidates suitable for protection of humans against organophosphorus-based toxicants. The results also permitted the refinement of a mathematical model for estimating the efficacious dose of rePON1s variants required for prophylaxis in humans.


► Ex vivo nerve agents detoxification capacity of rePON1 variants in human blood.
► Protection of AChE and BChE in human blood challenged ex vivo with cyclosarin.
► Screening for identification of rePON1 bioscavenger of organophosphate toxicants.
► Refinement of kinetic input for toxicokinetic models for estimating rePON1s dose.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 206, Issue 1, 25 September 2011, Pages 24–28
نویسندگان
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