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

IF 2.1 4区医学 Q3 CHEMISTRY, MULTIDISCIPLINARY

Drug and Chemical Toxicology Pub Date : 2025-01-27 DOI:10.1080/01480545.2025.2454279

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

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引用次数: 0

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 LD₅₀ 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% LD₅₀) 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.

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来源期刊

Drug and Chemical Toxicology 医学-毒理学

CiteScore

6.00

自引率

3.80%

发文量

审稿时长

3 months

期刊介绍： Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.