科研之友
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摘要
To examine the possible modifying effect of the extract of Siraitia grosvenori (SGE), a naturally occurring antioxidative agent, on piperonly butoxide (PBO)-promoted hepatocarcinogenesis, male F344 rats were administered a single intraperitoneal injection of N-diethylnitrosaminc (DEN) as an initiator followed by administration of a diet containing 2%PBO for 7 weeks with or without SGE (1,000 ppm) in the drinking water. To enhance cellular proliferation, all animals underwent two-thirds partial hepatectomy 1 week after the commencement of PBO administration. Pretreatment with SGE was also applied to the PBO + SGE group for 2 weeks prior to DEN initiation. Liver immunohistochemistry revealed that although the PBO-mediated increase in the number of glutathione S-transferase placental form (GST-P)-positive foci and proliferating cell nuclear antigen-positive cells remained unaltered with SGE coadministration. the area of the GST-P-positive foci was increased. On the countrary real-time RT-PCR showed that coadministration of SGE epresson levels of the phase II enzymes that are known to be transcriptionally up-regulated through the NrF2-Keapl-antioxidant responsive element (ARE) as well as the phase III enzymes. Furthermore, measurment of thiobarbituric acid-reactive substances showed a decrease in lipid peroxidation by SGE coadministration. The results suggest that SGE may exert hepatic antioxidant activity by up-regulating the genes under the control of the Nrf 2-KeapI-ARE transcriptional machinery: however, this activity was neither effective nor sufficient for suppression of PBO-promoted early hepatocarcinogenesis.
- 出版日期2008-5
