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DNA and RNA damage by Cu(II)-amikacin complex
Małgorzata Jezowska-Bojczuk1, Wojciech Szczepanik, Wojciech Leśniak
1Faculty of Chemistry, University of Wrocław, Wrocław, Poland; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland. MJB@wchuwr.chem.uni.wroc.pl
European Journal of Biochemistry
|November 9, 2002
Summary
The copper(II)-amikacin complex [Cu(II)-Ami] with hydrogen peroxide oxidizes DNA and RNA molecules. This reactivity is driven by hydroxyl radicals, leading to molecular damage.
Area of Science:
- Bioinorganic Chemistry
- Chemical Biology
- Molecular Toxicology
Background:
- Copper complexes can interact with biological molecules.
- Aminoglycosidic antibiotics like amikacin have unique chemical properties.
- Hydrogen peroxide is a reactive oxygen species with significant biological implications.
Purpose of the Study:
- To investigate the oxidation-promoting reactivity of the copper(II) complex of amikacin [Cu(II)-Ami].
- To identify the target molecules affected by this complex in the presence of hydrogen peroxide.
- To elucidate the reactive species responsible for the observed oxidation.
Main Methods:
- Studied the reactivity of [Cu(II)-Ami] with hydrogen peroxide at pH 7.4.
- Utilized 2'-deoxyguanosine (dG), pBR322 plasmid DNA, and yeast tRNAPhe as target substrates.
- Analyzed oxidation products and molecular damage.
Main Results:
- The [Cu(II)-Ami] complex efficiently oxidized dG to its 8-oxo derivative.
- Observed strand breaks in plasmid DNA and multiple cleavages in yeast tRNAPhe.
- The complex also underwent autooxidation, forming amikacin hydroperoxides.
Conclusions:
- The observed reactivity is attributed to both metal-bound and free hydroxyl radicals.
- [Cu(II)-Ami] in the presence of H2O2 acts as an efficient oxidant, causing significant damage to nucleic acids.
- Understanding this reactivity is crucial for assessing potential biological impacts of such complexes.