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 LD, 0.5 LD, and 1.0 LD 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 LD of each oxime, muscle fibres did not show any change. The intensive degeneration was found in all muscles after treatment with 0.5 LD of asoxime and obidoxime, respectively. Acute toxic muscle injury was developed within 7 days following treatment with 0.5 LD and 1.0 LD 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.
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| http://dx.doi.org/10.1038/s41598-018-37837-4 | DOI Listing |
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