Naslov
Cytotoxicity of oximes tested as antidotes in organophosphorus compound poisoning

Autori
Zandona, Antonio ; Zorbaz, Tamara ; Kovarik, Zrinka ; Katalinić, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
12th Meeting of the Slovenian Biochemical Society with International Participation, Book of Abstracts, 20-23 September 2017, Bled, Slovenia / Goričar, Katja ; Hudler, Petra - Ljubljana : Slovenian Biochemical Society, 2017, 82-82

ISBN
978-961-93879-4-8

Skup
12th Meeting of the Slovenian Biochemical Society with International Participation

Mjesto i datum
Bled, Slovenija, 20.09.2017. - 23.09.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Organophosphorus compounds ; Cholinesterase ; Oxime ; Cell viability ; Reactive oxygen species

Sažetak
Organophosphorus compounds (OPs) belong to a large group of compounds that include nerve agents, pesticides, industrially fire-resistant hydraulic fluids, coolants and lubricants. OPs cause irreversible inhibition of enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), thereby preventing the degradation of acetylcholine, essential in neurotransmission, which consequently leads to cholinergic crisis and death. Only compounds known as oximes have shown the ability to reactivate inhibited ChEs and are therefore used as antidotes in cases of OP poisoning. Development of more efficient oximes is currently an ongoing endeavor worldwide. However, little is known about possible effects on the cellular level of new oximes as well as about the adverse effects they could possibly induce. To improve the selection of a lead candidate for preclinical antidote development, we performed a set of cell-based assays with several oximes showing desirable ChE reactivation kinetics. We monitored cell viability and induction of reactive oxygen species (ROS) in various cell lines upon exposure to the selected oximes. Several of the newly-developed oximes significantly influenced cell viability and induced ROS changes in concentrations relevant for reactivation studies (IC50 ≤ 300 μM). The results were compared to the results obtained for oximes HI-6 and 2-PAM, currently used in practice, which did not show any cytotoxic effect or ROS induction within the studied concentration range (≤ 800 μM and 400 μM, respectively). Although the exact mechanism of the observed effects of the tested oximes is not clear and will be in the focus of our future research, such an unwanted effect on cells presents a major drawback to their further development as potential antidotes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA