Naslov
Irinotecan Side Effects Relieved by the Use of HI-6 Oxime : In Vivo Experimental Approach

Autori
Lucić Vrdoljak, Ana ; Berend, Suzana ; Želježić, Davor ; Žegarac-Piljac, Jasenka ; Pleština, Stjepko ; Kuča, Kamil ; Radić, Božica ; Mladinić, Marin ; Kopjar, Nevenka

Izvornik
Basic and Clinical Pharmacology and Toxicology (1742-7835) 105 (2009), 6; 401-409

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

Ključne riječi
irinotecan; HI-6; oxidative stress markers; DNA damage

Sažetak
Some compounds, although not primarily designed as supportive drugs in chemotherapy, are promising candidates for clinical use. The ability of HI-6 oxime to relieve the side effects of irinotecan was recently determined in vitro. In this animal study, we investigated the efficacy of HI-6 in vivo, when given as a pre-treatment and concomitantly with irinotecan. We evaluated the cholinesterase (ChE)/acetylcholinesterase (AChE) activity, the levels of oxidative stress markers, DNA damage and the radical scavenging capacity of HI-6. Both HI-6 and irinotecan inhibited ChE/AChE activity but showed different levels of ChE inhibition in plasma and AChE inhibition in the liver and brain tissue. We also observed a weak antioxidant capacity of HI-6, undiscovered until now, and found an acceptable genotoxicity profile in three types of somatic cells in rats. The in vivo erythrocyte micronucleus assay showed that HI-6 did not significantly change either the frequency of micronuclei or the ratio of polychromatic and normorchromatic erythrocytes. Taken together, our results provide a good argument in favour of HI-6 as a promising molecule for further studies and eventual use in humans.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA