Interspecies and intergender differences in acute toxicity of K-oximes drug candidates
Language English Country Ireland Media print-electronic
Document type Journal Article
PubMed
31153983
DOI
10.1016/j.cbi.2019.05.035
PII: S0009-2797(19)30368-0
Knihovny.cz E-resources
- Keywords
- Acute toxicity, K-oximes, LD(50), Mice, Rats,
- MeSH
- Acetylcholinesterase chemistry metabolism MeSH
- Rats MeSH
- Lethal Dose 50 MeSH
- Mice MeSH
- Obidoxime Chloride toxicity MeSH
- Oximes toxicity MeSH
- Rats, Wistar MeSH
- Prodrugs toxicity MeSH
- Cholinesterase Reactivators chemistry metabolism toxicity MeSH
- Toxicity Tests, Acute methods MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Obidoxime Chloride MeSH
- Oximes MeSH
- Prodrugs MeSH
- Cholinesterase Reactivators MeSH
K-oximes were developed as modern drug candidates acting as AChE reactivators. In this study, it has been investigated which interspecies and intergender differences changes could be observed in Wistar rats and Swiss mice, both genders, after the treatment with increasing doses of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, and K075. After the 24 h, a number of died animals was counted and the median lethal dose (LD50) for each oxime was calculated. By using the intramuscular route of administration, asoxime and K027 had the least toxicity in female rats (640.21 mg/kg and 686.08 mg/kg), and in female mice (565.75 mg/kg and 565.74 mg/kg), respectively. Moreover, asoxime and K027 showed 3, 4 or 8 times less acute toxicity in comparison to K048, obidoxime and K075, respectively. Beyond, K075 had the greatest toxicity in male rats (81.53 mg/kg), and in male mice (57.34 mg/kg), respectively. Our results can help to predict likely adverse toxic effects, target organ systems and possible outcome in the event of massive human overexposure, and in establishing risk categories or in dose selection for the initial repeated dose toxicity tests to be conducted for each oxime.
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