作者
Antonio Zandona, Josip Madunić, Katarina Miš, Nikola Maraković, Pierre Dubois-Geoffroy, Marco Cavaco, Petra Mišetić, Jasna Padovan, Miguel Castanho, Ludovic Jean, Pierre-Yves Renard, Sergej Pirkmajer, Vera Neves, Maja Katalinić
发表日期
2023/8/1
期刊
Toxicology
卷号
494
页码范围
153588
出版商
Elsevier
简介
The uncharged 3-hydroxy-2-pyridine aldoximes with protonatable tertiary amines are studied as antidotes in toxic organophosphates (OP) poisoning. Due to some of their specific structural features, we hypothesize that these compounds could exert diverse biological activity beyond their main scope of application. To examine this further, we performed an extensive cell-based assessment to determine their effects on human cells (SH-SY5Y, HEK293, HepG2, HK-2, myoblasts and myotubes) and possible mechanism of action. As our results indicated, aldoxime having a piperidine moiety did not induce significant toxicity up to 300 µM within 24 h, while those with a tetrahydroisoquinoline moiety, in the same concentration range, showed time-dependent effects and stimulated mitochondria-mediated activation of the intrinsic apoptosis pathway through ERK1/2 and p38-MAPK signaling and subsequent activation of …
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