Toxic Injury to Muscle Tissue of Rats Following Acute Oximes Exposure

Vesna Jaćević,Kamil Kuča,Eugenie Nepovimova

doi:10.1038/s41598-018-37837-4

Vesna Jaćević, Kamil Kuča + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-37837-4

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Abstract

Therapeutic application of newly developed oximes is limited due to their adverse effects on different tissues. Within this article, it has been investigated which morphological changes could be observed in Wistar rats after the treatment with increasing doses of selected acetyl cholinesterase reactivators - asoxime, obidoxime, K027, K048, and K075. Subsequently, heart, diaphragm and musculus popliteus were obtained for pathohistological and semiquantitative analysis 24 hrs and 7 days after im administration of a single dose of 0.1 LD50, 0.5 LD50, and 1.0 LD50 of each oxime. Different muscle damage score was based on an estimation scale from 0 (no damage) to 5 (strong damage). In rats treated with 0.1 LD50 of each oxime, muscle fibres did not show any change. The intensive degeneration was found in all muscles after treatment with 0.5 LD50 of asoxime and obidoxime, respectively. Acute toxic muscle injury was developed within 7 days following treatment with 0.5 LD50 and 1.0 LD50 of each oxime, with the highest values in K048 and K075 group (P < 0.001 vs. control and asoxime), respectively. The early muscle alterations observed in our study seem to contribute to the pathogenesis of the oxime-induced toxic muscle injury, which probably manifests as necrosis and/or inflammation.

Highlights

Acetylcholinesterase (AChE) reactivators, called oximes, were developed for the treatment of organophosphorus poisoning (OP)[1,2,3,4]
The promising approach for the determination of acute toxicity in experimental animals is by using a single dose of a chemical wherein lethality (i.e. LD50) can be determined within 24 hrsstudies[38,39]
Our study reports the acute toxicity of asoxime, obidoxime, K027, K048, and K075 using the intramuscular route of exposure in Wistar rats

Summary

Introduction

Acetylcholinesterase (AChE) reactivators, called oximes, were developed for the treatment of organophosphorus poisoning (OP)[1,2,3,4]. In the groups of animals treated with obidoxime, K048 or K075, the presence of moderate myofibril degeneration, hyperaemia, haemorrhages and tissue accumulation of neutrophils and macrophages were noticed focally. A single administration of a median lethal dose of asoxime, obidoxime, K027, K048 or K075 caused severe, diffuse and massive degenerative and vascular alterations in all treated animals.

Results

Conclusion