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Pregled bibliografske jedinice broj: 257491

The toxic effects of irinotecan on human erythrocyte AChE in vitro


Lucić Vrdoljak, Ana; Radić, Božica; Kopjar, Nevenka; Želježić, Davor; Milas, Ivan; Petek, Maja Jelena
The toxic effects of irinotecan on human erythrocyte AChE in vitro // Abstracts of the EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries ; u: Toxicology Letters. Supllement 164 (2006) (S1) S1-S324 / Kniewald, Jasna (ur.).
Cavtat, Hrvatska, 2006. str. S218-S219 (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
The toxic effects of irinotecan on human erythrocyte AChE in vitro

Autori
Lucić Vrdoljak, Ana ; Radić, Božica ; Kopjar, Nevenka ; Želježić, Davor ; Milas, Ivan ; Petek, Maja Jelena

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

Izvornik
Abstracts of the EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries ; u: Toxicology Letters. Supllement 164 (2006) (S1) S1-S324 / Kniewald, Jasna - , 2006, S218-S219

Skup
Congress of the European Societies of Toxicology (43 ; 2006) ; Congress of Toxicology in Developing Countries (6 ; 2006)

Mjesto i datum
Cavtat, Hrvatska, 20.-24.09.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Irinotecan; in vitro toxicity; AChE; physostigmine

Sažetak
The best-characterised function of AChE is the hydrolysis of acetylcholine (ACh) at cholinergic synapses. Inhibition of its enzyme leads to an accumulation of ACh resulting in an over-stimulation of the whole cholinergic system. Muscular and nerve AChE are only present in the synaptic cleft and cannot be measured directly. Since erythrocyte AChE has a similar structure as the synaptic enzyme, it appears to be a suitable parameter to reflect the various reactions at the synaptic site. Therefore its 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. Irinotecan is one of the most important new anticancer drugs developed in the last few decades. It has undergone extensive clinical investigation worldwide and demonstrated potent activity against many types of human cancer, in particular, gastrointestinal and pulmonary malignancies, but also leukemia and lymphomas, as well as central nervous system malignant gliomas. The principal dose-limiting toxicity of irinotecan is diarrhoea related to a cholinergic surge from inhibition of AChE. In our experiments, the inhibitory power (IC50) of irinotecan on AChE of human erythrocytes is determined and compared with physostigmine which is tested as reference drug. IC50 values were 5.0 x 10^-7 for irinotecan and 2.0 x 10^-8 mol/l for physostigmine. Also, a continuous decrease of catalytic activity of human erythrocyte AChE was obtained 10, 30, 60, 120, 150 and 180 minutes after addition doses of irinotecan recommended as monotherapy in adult patients (9.0 and 4.6 μ g/ml). A higher dose of irinotecan inhibited the AChE activity with potency similar to that estimated for the physostigmine, and there was a slight reduction in the inhibition of AChE by both of doses of irinotecan with increased incubation times. In conclusion, the inhibition of AChE activity seems to be connected with administration of irinotecan. Judging from experimental in vitro data, we believe that in addition to the measurement of AChE activity, it would be appropriate to control acute cholinergic syndrome in patients with carcinoma.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
0022015
0022019

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