Interspecies and intergender differences in acute toxicity of K-oximes drug candidates
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
31153983
DOI
10.1016/j.cbi.2019.05.035
PII: S0009-2797(19)30368-0
Knihovny.cz E-zdroje
- Klíčová slova
- Acute toxicity, K-oximes, LD(50), Mice, Rats,
- MeSH
- acetylcholinesterasa chemie metabolismus MeSH
- krysa rodu Rattus MeSH
- LD50 MeSH
- myši MeSH
- obidoxim chlorid toxicita MeSH
- oximy toxicita MeSH
- potkani Wistar MeSH
- prekurzory léčiv toxicita MeSH
- reaktivátory cholinesterasy chemie metabolismus toxicita MeSH
- testy akutní toxicity metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- obidoxim chlorid MeSH
- oximy MeSH
- prekurzory léčiv MeSH
- reaktivátory cholinesterasy 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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