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Publications

Journal Article Ahead of print

PubMed: 39871446 DOI: 10.1080/01480545.2025.2454279

Novel chlorinated oxime K870 protects rats against paraoxon poisoning better than obidoxime.

Drug Chem Toxicol

Authors: Žana M Maksimović, Sonja T Marinković, Đorđe Đukanović, Nebojša Mandić-Kovačević, Snežana Uletilović, Mladen Duran, Kamil Kuča, Kamil Musilek, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković

Affiliations

  • Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina.
  • Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina.
  • Paediatric Clinic, University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina.
  • Department of Pharmacy, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina.
  • Department of Medical Biochemistry and Chemistry, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina.
  • Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
  • Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
  • Department of Anaesthesiology and Reanimatology, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina.

Abstract

The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.

MeSH

Erythrocytes, Organophosphates, Poisoning, Brain, Paraoxon, Liver, Cerebellum, Brain Stem, Toxicology, Diaphragm, Atropine, Plasma, Cerebrum, Oximes