文章基本信息

标题：Oxidative Stress Induced by a Dihydropyrazine Derivative
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作者：Shinji Takechi ; Kazuhide Nakahara ; Masaru Adachi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：2
页码：186-189
DOI：10.1248/bpb.32.186
出版社：The Pharmaceutical Society of Japan
摘要：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 in vitro . 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 ( endo -type) and 1,2,3,5,6,7-hexahydroquinoxaline ( exo -type), fused with a cyclohexyl ring. Cyclohexyl-DHP caused DNA strand breaks in plasmid pUC18, especially in the presence of Cu²⁺. By using Escherichia coli mutant strains, we observed that cyclohexyl-DHP exposure strongly reduced the survival rate of a cytosolic sodium dodecyl sulfate (SOD)-deficient strain ( sodA sodB ), significantly reduced the survival rates of DNA repair-deficient strains ( recA and uvrB ) and mildly reduced the survival rate of a catalase-deficient strain ( katE katG ) compared with the survival rate of the wild-type strain. Addition of Cu²⁺ enhanced the cell killing ability of cyclohexyl-DHP. The frequency of mutations induced by cyclohexyl-DHP increased dose-dependently in the sodA sodB 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 E. coli . 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.
关键词：dihydropyrazine;Escherichia coli;DNA damage;mutagenicity;superoxide anion;protein oxidation