TY - JOUR
T1 - In vivo detection of free radicals induced by diethylnitrosamine in rat liver tissue
AU - Yamada, Ken ichi
AU - Yamamiya, Ikuo
AU - Utsumi, Hideo
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. We thank Dr. Keizo Takeshita for technical advice on the spin trapping technique.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.freeradbiomed.2006.01.031
DO - 10.1016/j.freeradbiomed.2006.01.031
M3 - Article
C2 - 16716904
AN - SCOPUS:33646588337
SN - 0891-5849
VL - 40
SP - 2040
EP - 2046
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 11
ER -
