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Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its possible cyto / genotoxicity in vitro (CROSBI ID 133916)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Radić, Božica ; Lucić Vrdoljak, Ana ; Želježić, Davor ; Fuchs, Nino ; Berend, Suzana ; Kopjar, Nevenka Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its possible cyto / genotoxicity in vitro // Acta biochimica Polonica, 54 (2007), 3; 583-593

Podaci o odgovornosti

Radić, Božica ; Lucić Vrdoljak, Ana ; Želježić, Davor ; Fuchs, Nino ; Berend, Suzana ; Kopjar, Nevenka

engleski

Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its possible cyto / genotoxicity in vitro

The function of acetylcholinesterase (AChE) is the rapid hydrolysis of the neurotransmitter acetylcholine (ACh), which is involved in the numerous cholinergic pathways in both, the central and the peripheral nervous system. Therefore, AChE measurement is of high value for therapy management, especially during the course of the intoxication with different chemicals or drugs that inhibits activity of enzyme. Different substances, pyridinium or bispyridinium aldoximes (oximes) among them, are able for the recovery of inhibited enzyme. Since their adverse effects are not well elucidated, in this study the efficiency of HI-6 oxime in protection and/or reactivation of human erythrocyte (AChE) inhibited by antineoplastic drug irinotecan as well as its cyto / genotoxicity in vitro were investigated. HI-6 increases the activity of AChE to 30% ; residual activity after irinotecan inhibition was 7%. Also, it reactivated the enzyme previously inhibited by irinotecan (4.6 mg/ml) by 50% when applied in a concentration of ¼ of the IC50 value. Tested concentrations of HI-6 exhibited acceptable genotoxicity on white blood cells, as estimated by the alkaline comet assay, DNA diffusion assay and cytogenetic endpoints (structural chromosome aberrations and cytokinesis-block micrunucleus assay). The results obtained sustain the further investigation of HI-6 in vivo, as well as its development for possible application in chemotherapy.

Hi-6; Acetylcholinesterase; Irinotecan; Protection; Reactivation; Comet assay; Chromosome aberrations; apoptosis; Micronuclei

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Podaci o izdanju

54 (3)

2007.

583-593

objavljeno

0001-527X

Povezanost rada

Temeljne medicinske znanosti

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