TAILIEUCHUNG - Báo cáo Y học: DNA and RNA damage by Cu(II)-amikacin complex

Theoxidation-promotingreactivityof copper(II) complexof aminoglycosidic antibiotic amikacin [Cu(II)-Ami] in the presence of hydrogen peroxide, was studied at pH , using 2¢-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNA Phe as target molecules. Themixtures of complexwith H2O2were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNA Phe . | Eur. J. Biochem. 269 5547-5556 2002 FEBS 2002 doi DNA and RNA damage by Cu II -amikacin complex Matgorzata Jezowska-Bojczuk1 Wojciech Szczepanik1 Wojciech Lesniak1 Jerzy Ciesiotka2 Jan Wrzesinski2 and Wojciech Bal3 1 Faculty of Chemistry University of Wroclaw Wroclaw Poland 2Institute of Bioorganic Chemistry Polish Academy of Sciences Poznan Poland 3Institute of Biochemistry and Biophysics Polish Academy of Sciences Warsaw Poland The oxidation-promoting reactivity of copper II complex of aminoglycosidic antibiotic amikacin Cu II -Ami in the presence of hydrogen peroxide was studied at pH using 2 -deoxyguanosine dG pBR322 plasmid DNA and yeast tRNAPhe as target molecules. The mixtures of complex with H2O2 were found to be efficient oxidants converting dG to its 8-oxo derivative generating strand breaks in plasmid DNA and multiple cleavages in tRNAPhe. The complex underwent autooxidation as well with amikacin hydroperoxides as likely major products. This reactivity pattern was found to be due to a combination of metal-bound and free hydroxyl radicals. Keywords copper II complexes amikacin 2 -deoxyguano-sine oxidation plasmid DNA damage tRNA cleavage. Amikacin Ami is a semisynthetic aminoglycoside a derivative of kanamycin A having the B1 amino group of 2-deoxystreptamine moiety modified by acylation with 4-amino-2-hydroxybutyric acid. Previous studies demonstrated that Ami is a strong chelator for Cu II ions 1 2 . Cu II is coordinated at B ring which is in contrast with unsubstituted aminoglycosides where terminal aminosugar rings are involved in the binding 3-11 . In the presence of H2O2 the Cu II -Ami complex oxidizes 2 -deoxyguanosine to its 8-oxo derivative 1 . Recently we presented the mechanism of such H2O2 activation which involves generation of hydroxyl radicals 12 . Antimicrobial action of Ami and other aminoglycosides is based on their interactions with ribosomal RNA 13 and also with cytoplasmic membrane 14 15 . .

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