Oxidative Stress Induced by a Dihydropyrazine Derivative

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Abstract

The Maillard reaction contributes to the complications of diabetes and normal aging. Dihydropyrazines (DHPs), which are produced during the Maillard reaction, generate radicals and possess DNA strand-cleaving activities <i>in vitro</i>. In the present study, we evaluated the genotoxic and cytotoxic potentials of a DHP derivative, cyclohexyl-DHP, which is obtained as a mixture of two isomers, 2,3,5,6,7,8-hexahydroquinoxaline (<i>endo</i>-type) and 1,2,3,5,6,7-hexahydroquinoxaline (<i>exo</i>-type), fused with a cyclohexyl ring. Cyclohexyl-DHP caused DNA strand breaks in plasmid pUC18, especially in the presence of Cu<sup>2+</sup>. By using <i>Escherichia coli</i> mutant strains, we observed that cyclohexyl-DHP exposure strongly reduced the survival rate of a cytosolic sodium dodecyl sulfate (SOD)-deficient strain (<i>sodA sodB</i>), significantly reduced the survival rates of DNA repair-deficient strains (<i>recA</i> and <i>uvrB</i>) and mildly reduced the survival rate of a catalase-deficient strain (<i>katE katG</i>) compared with the survival rate of the wild-type strain. Addition of Cu<sup>2+</sup> enhanced the cell killing ability of cyclohexyl-DHP. The frequency of mutations induced by cyclohexyl-DHP increased dose-dependently in the <i>sodA sodB</i> strain. Assays with the highly water-soluble tetrazolium salt WST-1 revealed that cyclohexyl-DHP strongly generated superoxide anions. Moreover, cyclohexyl-DHP elevated the protein carbonyl levels in <i>E. coli</i>. These findings indicate that cyclohexyl-DHP could potentially generate superoxide anions, and cause not only breakage of chromosomal DNA leading to mutagenic lesions but also induce damage to cellular proteins.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 32(2), 186-189, 2009-02-01

    The Pharmaceutical Society of Japan

References:  28

Cited by:  1

Codes

  • NII Article ID (NAID)
    110007042165
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09186158
  • NDL Article ID
    9775076
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  CJPref  NDL  NII-ELS  J-STAGE 
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