Dietary catechol causes increased oxidative DNA damage in the livers of mice treated with acetaminophen |
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Authors: | Yuji Ishii Toshiya Okamura Tomoki Inoue Masako Tasaki Takashi Umemura Akiyoshi Nishikawa |
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Affiliation: | aDivision of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan |
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Abstract: | We have shown that direct reaction of catechol with nitric oxide (NO) results in generation of reactive oxygen and nitrogen species (RNS) through semiquinone radical formation, leading to oxidative DNA damage in rat forestomach. In the present study, we investigated whether dietary catechol systemically exerts the same effects under NO-rich circumstances, when given before and during induction of inflammatory lesions. Male ICR mice were treated with or without 0.8% catechol in the diet for 2 weeks followed by acetaminophen (APAP) administration at a dose of 300 mg/kg by single i.p. injection. Along with several indicators of APAP-induced hepatitis, 8-hydroxydeoxyguanosine (8-OHdG) levels and immunohistochemistry for 3-nitrotyrosine (NO2Tyr) in the livers were examined at 1.5, 4 and 24 h after APAP injection. 8-OHdG was significantly increased at 24 h in the co-treatment group, but not with either catechol or APAP alone. Elevation of serum ALT and AST activities, decrease of reduced glutathione levels and histopathological liver changes were observed to the same extents in both APAP-treated groups. In view of the finding of positive hepatocytes for NO2Tyr prior to generation of 8-OHdG, the process of oxidative DNA damage might involve RNS formation. Precise quantitative analysis of NO2Tyr by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS) in an additional study with the same experimental protocol confirmed increase of RNS due to the reaction of catechol with NO produced after APAP-induced hepatitis. The overall data imply that antioxidants with a catechol structure can cause oxidative DNA damage under inflammatory conditions. |
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Keywords: | Catechol Acetaminophen Nitric oxide Peroxynitrite |
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