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Irinotecan Side Effects Relieved by the Use of HI‐6 Oxime: In Vivo Experimental Approach
Author(s) -
Vrdoljak Ana Lucić,
Berend Suzana,
Želježić Davor,
PiljacŽegarac Jasenka,
Pleština Stjepko,
Kuča Kamil,
Radić Božica,
Mladinić Marin,
Kopjar Nevenka
Publication year - 2009
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2009.00460.x
Subject(s) - in vivo , irinotecan , acetylcholinesterase , cholinesterase , micronucleus test , pharmacology , genotoxicity , butyrylcholinesterase , oxidative stress , antioxidant , chemistry , in vitro , aché , toxicity , biochemistry , biology , enzyme , medicine , cancer , genetics , colorectal cancer , organic chemistry
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.