The estimation of oxime efficiency is affected by the experimental design of phosphylated acetylcholinesterase reactivation. (1st September 2018)

• Record Type: Journal Article
• Authors: Maček Hrvat, Nikolina; Zorbaz, Tamara; Šinko, Goran; Kovarik, Zrinka
• Is Part Of: Toxicology letters. Volume 293(2018)
• Page Start: 222
• Page End: 228
• Publication Date: 2018-09-01
• Subjects: Cholinesterase -- 2-PAM -- HI-6 -- Sarin -- Nerve agent -- Ellman assay; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.11.022
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: A wide oxime concentration range is needed for an accurate evaluation of reactivation constants. Reactivation efficiency depends on the enzyme concentration in the assay. Oxime side-reactions could affect the reactivation. Abstract: Reactivation of acetylcholinesterase (AChE), an essential enzyme in neurotransmission, is a key point in the treatment of acute poisoning by nerve agents and pesticides, which structurally belong to organophosphorus compounds (OP). Due to the high diversity of substituents on the phosphorous atom, there is a variety of OP-AChE conjugates deriving from AChE inhibition, and therefore not only is there no universal reactivator efficient enough for the most toxic OPs, but for some nerve agents there is still a lack of any reactivator at all. The endeavor of many chemists to find more efficient reactivators resulted in thousands of newly-designed and synthesized oximes−potential reactivators of AChE. For an evaluation of the oximés reactivation efficiency, many research groups employ a simple spectrophotometric Ellman method. Since parameters that describe reactivator efficiency are often incomparable among laboratories, we tried to emphasize the critical steps in the determination of reactivation parameters as well as in the experimental design of a reactivation assay. We highlighted the important points in evaluation of reactivation kinetic parameters with an aim to achieve better agreement and comparability between the results obtained by different laboratories and overall, a more efficient evaluation of in vitro reactivation potency.