Title : Irinotecan side effects relieved by the use of HI-6 oxime: in vivo experimental approach - Vrdoljak_2009_Basic.Clin.Pharmacol.Toxicol_105_401 |
Author(s) : Vrdoljak AL , Zunec S , Zeljezic D , Piljac-Zegarac J , Plestina S , Kuca K , Radic B , Mladinic M , Kopjar N |
Ref : Basic Clin Pharmacol Toxicol , 105 :401 , 2009 |
Abstract :
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. |
PubMedSearch : Vrdoljak_2009_Basic.Clin.Pharmacol.Toxicol_105_401 |
PubMedID: 19663821 |
Vrdoljak AL, Zunec S, Zeljezic D, Piljac-Zegarac J, Plestina S, Kuca K, Radic B, Mladinic M, Kopjar N (2009)
Irinotecan side effects relieved by the use of HI-6 oxime: in vivo experimental approach
Basic Clin Pharmacol Toxicol
105 :401
Vrdoljak AL, Zunec S, Zeljezic D, Piljac-Zegarac J, Plestina S, Kuca K, Radic B, Mladinic M, Kopjar N (2009)
Basic Clin Pharmacol Toxicol
105 :401