Naslov
Effects of oxime K048 on acetylcholinesterase activity and oxidative response in tabun exposed rats

Autori
Žunec, Suzana ; Lucić Vrdoljak, Ana ; Kopjar, Nevenka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Joint Scientific Symposium of the Austrian Societies of Toxicology (ASTOX), Pharmacy (ÖPhG), Analytic Chemistry (ASAC), and Forensic Medicine (ÖGGM), and the Comprehensive Cancer Center Vienna (CCC) / - Beč, 2013

Skup
Joint Scientific Symposium of the Austrian Societies of Toxicology (ASTOX), Pharmacy (ÖPhG), Analytic Chemistry (ASAC), and Forensic Medicine (ÖGGM), and the Comprehensive Cancer Center Vienna (CCC)

Mjesto i datum
Beč, Austrija, 21.03.2013. - 22.03.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
organophosphorous (OP) compounds; pesticides; effective antidote

Sažetak
The widespread use of organophosphorous (OP) compounds as pesticides and the misuse of nerve agents emphasize the need for effective antidotal preparedness. The toxic symptomatology of OP is caused primarily by irreversible inhibition of the serine-protease acetylcholinesterase (AChE), but the data on OP overall mechanisms of toxicity are still incomplete. Anticholinergics such as atropine and AChE reactivators - oximes are used as first aid antidotes for OP intoxications. However, reactivation by oximes is not possible in all cases of OP poisoning, especially in the case of nerve agent tabun. Objectives: To evaluate the efficiency of oxime K048 as therapy against tabun poisoning and to study whether the oxidative stress is involved in the mechanism of OP toxic effects. Methods: Male rats were injected subcutaneously with sublethal dose of tabun, and treated intraperitoneally 1 min later with K048 plus atropine. Plasma and tissue samples were analyzed for AChE activity and levels of oxidative stress and DNA damage (lipid peroxidation, superoxide dismutase and the alkaline comet assay). Results and Discussion: Tabun exposure resulted with a high degree of AChE inhibition (~90% in the plasma and 75% in the brain). Therapy combined of K048 and atropine efficiently counteracted tabun poisoning by restoring ~50% of AChE activity in plasma up to 1 h. This result indicates good reactivation potential of oxime K048. Beside anticholinesterase activity, tabun showed stressogenic effects by increasing LPO, SOD activity and primary DNA damage in the brain during 24 h exposure. We can conclude that tabun poisoning caused an excessive formation of free radicals which could associate oxidative stress with the nerve agent’s neurotoxicity.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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