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Cytotoxicity of oximes tested as antidotes in organophosphorus compound poisoning (CROSBI ID 652511)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa

Zandona, Antonio ; Zorbaz, Tamara ; Kovarik, Zrinka ; Katalinić, Maja Cytotoxicity of oximes tested as antidotes in organophosphorus compound poisoning // 12th Meeting of the Slovenian Biochemical Society with International Participation, Book of Abstracts, 20-23 September 2017, Bled, Slovenia / Goričar, Katja ; Hudler, Petra (ur.). Ljubljana: Slovenian Biochemical Society, 2017. str. 82-82

Podaci o odgovornosti

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

engleski

Cytotoxicity of oximes tested as antidotes in organophosphorus compound poisoning

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.

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

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Podaci o prilogu

82-82.

2017.

objavljeno

Podaci o matičnoj publikaciji

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

978-961-93879-4-8

Podaci o skupu

12th Meeting of the SlovenianBiochemical Society with International Participation

poster

20.09.2017-23.09.2017

Bled, Slovenija

Povezanost rada

Kemija, Biologija