Experimental and established oximes as pretreatment before acute exposure to azinphos-methyl

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F21%3A50017953" target="_blank" >RIV/62690094:18470/21:50017953 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/22/6/3072" target="_blank" >https://www.mdpi.com/1422-0067/22/6/3072</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms22063072" target="_blank" >10.3390/ijms22063072</a>

Result language

angličtina

Original language name

Experimental and established oximes as pretreatment before acute exposure to azinphos-methyl

Original language description

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International journal of molecular sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

22

Issue of the periodical within the volume

6

Country of publishing house

CH - SWITZERLAND

Number of pages

12

Pages from-to

"Article number 3072"

UT code for WoS article

000645732900001

EID of the result in the Scopus database

2-s2.0-85102551214