In vivo detection of free radicals induced by diethylnitrosamine in rat liver tissue.
In vivo detection of free radicals induced by diethylnitrosamine in rat liver tissue.
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DOI：
10.1016/j.freeradbiomed.2006.01.031
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发表时间：
2006-06
影响因子：
7.4
通讯作者：
Ken‐ichi Yamada;I. Yamamiya;H. Utsumi
中科院分区：
文献类型：
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作者：
Ken‐ichi Yamada;I. Yamamiya;H. Utsumi
二乙基亚硝胺（DEN）是一种众所周知的致癌物质，它需要微粒体激活才能与DNA反应导致突变和癌症。本研究的目的是利用体内自旋捕获和自旋探针技术来研究DEN激活过程中大鼠肝组织中是否产生自由基。我们采用α-苯基-正叔丁基硝基酮（PBN）作为自旋捕获剂，在给药前通过腹腔注射给药。DEN给药1小时后，检测胆汁中多组分PBN加合物，细胞色素P450抑制剂SKF-525A可降低其强度。ESR信号的计算机模拟揭示了脂质衍生自由基的存在。利用体内自旋探针/ESR技术，den处理组甲氧羰基- proxyl的信号衰减率明显高于载药组。PBN和/或SKF-525A预处理可以恢复增强的信号衰减率。这些结果表明，DEN给药后1 h内肝脏产生脂质自由基。
Diethylnitrosamine (DEN) is a well-known carcinogenic substance that requires microsomal activation before it can react with DNA to cause mutations and cancer. The aim of this study was to use in vivo spin trapping and spin probe techniques to investigate whether free radicals are generated in rat liver tissue during DEN activation. We used α-phenyl-n-tert-butylnitrone (PBN) as the spin trapping agent, which was delivered through an intraperitoneal injection before DEN administration. One hour after DEN administration, multicomponent PBN adducts in the bile were detected, and the intensities were diminished by the cytochrome P450 inhibitor SKF-525A. A computer simulation of the ESR signals revealed the presence of a lipid-derived radical. Using the in vivo spin probe/ESR technique, the signal decay rate of methoxycarbonyl-PROXYL was significantly increased in the DEN-treated group compared with the rate in the vehicle group. The enhanced signal decay rate was restored with PBN and/or SKF-525A pretreatment. These results suggested that lipid-derived free radicals were generated in the liver within 1 h after DEN administration.