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


Lucić Vrdoljak, Ana; Berend, Suzana; Želježić, Davor; Žegarac-Piljac, Jasenka; Pleština, Stjepko; Kuča, Kamil; Radić, Božica; Mladinić, Marin; Kopjar, Nevenka
Irinotecan Side Effects Relieved by the Use of HI-6 Oxime : In Vivo Experimental Approach // Basic and Clinical Pharmacology and Toxicology, 105 (2009), 6; 401-409 doi:www3.interscience.wiley.com/user/accessdenied?ID=122539342&Act=2138&Code=4719&Page=/cgi-bin/fulltext/122539342/PDFSTART (međunarodna recenzija, članak, znanstveni)


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


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, )
108-1080058-0047 - Molekularni biljezi u solidnim tumorima - prediktivni i prognostički značaj (Stjepko Pleština, )

Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Medicinski fakultet, 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


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