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Pregled bibliografske jedinice broj: 690540

In Vivo Evaluation of Cholinesterase Activity, Oxidative Stress Markers, Cyto- and Genotoxicity of K048 Oxime – a Promising Antidote against Organophosphate Poisoning


Žunec, Suzana; Kopjar, Nevenka; Želježić, Davor; Kuča, Kamil; Musilek, Kamil; Lucić Vrdoljak, Ana
In Vivo Evaluation of Cholinesterase Activity, Oxidative Stress Markers, Cyto- and Genotoxicity of K048 Oxime – a Promising Antidote against Organophosphate Poisoning // Basic & clinical pharmacology & toxicology, 114 (2014), 4; 344-351 doi:10.1111/bcpt.12158 (međunarodna recenzija, članak, znanstveni)


Naslov
In Vivo Evaluation of Cholinesterase Activity, Oxidative Stress Markers, Cyto- and Genotoxicity of K048 Oxime – a Promising Antidote against Organophosphate Poisoning

Autori
Žunec, Suzana ; Kopjar, Nevenka ; Želježić, Davor ; Kuča, Kamil ; Musilek, Kamil ; Lucić Vrdoljak, Ana

Izvornik
Basic & clinical pharmacology & toxicology (1742-7835) 114 (2014), 4; 344-351

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cholinesterase activity; Cytotoxicity; Genotoxicity; In vivo; K048; Oxidative stress markers; Oxime; Rat

Sažetak
K048 is a member of K-oximes, a new oxime class that has recently been confirmed effective against poisoning by the nerve agent tabun and several pesticides. The toxicity profile of the K048 oxime has not been fully characterized and its optimal therapeutic dose has not yet been established. Earlier studies report excellent results with K048 in reactivating tabun-phosphorylated AChE and in the therapy of tabun-poisoned mice. It possesses a low acute toxicity and exerts an acceptable toxicity profile on isolated human peripheral blood lymphocytes in vitro. Intraperitoneal administration of K048 in rats resulted in an LD50 of 238.3 mg/kg. In this in vivo study, we investigated cholinesterase (ChE) activity and oxidative stress marker levels (lipid peroxidation and superoxide dismutase activity) in the plasma of exposed rats after administering the compound at 25% of its LD50. Lymphocyte viability was evaluated using an acridine orange/ethidium bromide in situ fluorescent assay. The levels of primary DNA damage in rat white blood cells were measured using the alkaline comet assay. The compound applied at 25% of its LD50 did not significantly affect ChE activity and lipid peroxidation and did not cause significant changes in the SOD activity in plasma. The cytotoxicity profile of K048 in the tested dose was also acceptable, and it did not possess significant DNA-damaging potential. The obtained results are promising for further evaluations of the K048 oxime, which should include tests on a broader concentration range and longer incubation times.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Farmacija



POVEZANOST RADA


Projekt / tema
022-0222148-2137 - Genotoksičnost kemijskih i fizikalnih agensa prirodnog i antropogenog podrijetla (Vilena Kašuba, )
022-0222148-2139 - Terapijski učinak novosintetiziranih spojeva pri otrovanju organofosfatima (Ana Lucić Vrdoljak, )

Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • BIOSIS Previews (Biological Abstracts)
  • CAB Abstracts
  • EMBASE (Excerpta Medica)
  • MEDLINE
  • Neurosciences Abstracts


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