J Appl Biomed 12:25-29, 2014 | DOI: 10.1016/j.jab.2013.01.001

Entry of oxime K027 into the different parts of rat brain: Comparison with obidoxime and oxime HI-6

Jana Žďárová Karasová^a,c,*, Filip Zemek^b, Jiří Kassa^b, Kamil Kuča^c

^a Department of Public Health, Faculty of Military Health Sciences, Hradec Králové, Czech Republic

^b Department of Toxicology, Faculty of Military Health Sciences, Hradec Králové, Czech Republic

^c Biomedical Research Center, University Hospital, Hradec Králové, Czech Republic

Acetylcholinesterase reactivators (oximes) are highly hydrophilic compounds. This factor is considered to limit their distribution through the human body, especially into the central nervous system. However, some results contradict this hypothesis and confirm low concentrations of oximes inside the CNS. This study aims to verify oxime penetration through the blood-brain barrier, and into different brain regions.
It has been confirmed that oximes can penetrate the BBB after therapeutic dose administration (0.73%, 0.69%, and 0.52% corresponding to obidoxime, HI-6, and new oxime K027). Although the whole brain level of K027 seems to be lower compared with other oximes we have to keep in mind that these numbers represent only a percentage of the concentration found in plasma. So, for more adequate comparison it is essential to have a look at the actual concentration of oximes in the wet brain tissue: 106.6 ± 19.87 ng/g (K027), 49.88 ± 10.21 ng/g (obidoxime) and 86.51 ± 42.37 ng/g (HI-6), where concentration of K027 was one order of magnitude higher than obidoxime and HI-6.
In spite of the fact that the distribution of oximes into the CNS is minimal and concentrations differ from section to section, reasonable reactivation should still occur.

Keywords: AChE; Obidoxime; HI-6; K027; BBB; HPLC

Received: January 14, 2013; Revised: January 28, 2013; Accepted: March 18, 2013; Published: January 1, 2014  Show citation