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Synthesis and Evaluation of Halogenated Pralidoximes in Reactivation of Organophosphate-Inhibited Cholinesterases.
ACS Med Chem Lett
December 2024
University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic.
Organophosphorus compounds are highly toxic irreversible inhibitors of cholinesterases, causing the disruption of cholinergic functions. Treatment of poisoning includes causal antidotes (oximes) used as reactivators of inhibited cholinesterases, such as pralidoxime. In this work, new halogenated oxime reactivators derived from pralidoxime were developed.
View Article and Find Full Text PDFAcute Paraoxon-Induced Neurotoxicity in a Mouse Survival Model: Oxidative Stress, Dopaminergic System Alterations and Memory Deficits.
Int J Mol Sci
November 2024
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.
Article Synopsis
- The study investigates the secondary neurotoxicity resulting from severe organophosphorus (OP) poisoning, specifically paraoxon (POX), and its impact on cognitive functions in surviving mice.
- Mice were injected with POX followed by various treatments, resulting in high survival rates but significant neurological changes such as increased lipid peroxidation and alterations in neurotransmitter levels in key brain areas linked to memory.
- Despite no signs of depression or anxiety, the study found long-term memory impairments in the mice, highlighting the model's usefulness for exploring the effects of OP exposure and strategies to combat associated cognitive deficits.
Rational design to enhance the catalytic activity of acetylcholinesterase and mitigate trichlorfon toxicity in vitro.
Int J Biol Macromol
December 2024
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Li-Hu Road, Bin-Hu District, Wuxi, Jiangsu, China. Electronic address:
Trichlorfon (TCF) is a widely used organophosphate pesticide whose inhibition of acetylcholinesterase (AChE) results in neurotoxicity and significant biosafety risks. Addressing these concerns requires effective strategies to mitigate TCF-induced toxicity and safeguard exposed organisms. In this study, we explored the potential of a catalytic activity enhanced Culex pipiens AChE mutant to mitigate TCF-induced cytotoxicity through rational design.
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