Nishimura Jihei, Dewa Yasuaki, Jin Meilan, Saegusa Yukie, Kawai Masaomi, Kemmochi Sayaka, Shimamoto Keisuke, Harada Tomoaki, Itoh Tadashi, Shima Tomomi, Shibutani Makoto, Mitsumori Kunitoshi
J Toxicol Pathol. 2009 Dec;22(4):255-61. doi: 10.1293/tox.22.255. Epub 2009 Dec 21.
To clarify the modifying effect of N-Acetyl-L-Cysteine (NAC), which has antioxidative ability, on hepatocarcinogenesis promoted by fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR) alpha agonist , male F344/N rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) as an initiator followed by administration of a diet containing 3,000 ppm of FF for 16 weeks. Two-thirds partial hepatectomy was performed 1 week after the FF treatment. Additionally, NAC treatments for 14 weeks from 2 weeks after the FF treatment were performed. Although the expression level of tumor protein p53 (Tp53) mRNA decreased in the DEN+FF+NAC group as compared with that in the DEN+FF group, no significant differences between the DEN+FF and DEN+FF+NAC groups were observed in the number of hepatocellular altered foci and activities of hepatocellular proliferation. In addition, the results of an antioxidant enzyme assay and measurement of the amounts of total glutathione in the liver revealed no significant difference between the DEN+FF and DEN+FF+NAC groups; although no significant differences were observed in many genes between the DEN+FF and DEN+FF+NAC groups, only glutathione peroxidase 2 (Gpx2) mRNA increased in the DEN+FF+NAC group as compared with the DEN+FF group. The results under the present experimental conditions indicate no obvious modifying effect of NAC on liver tumor promotion by FF in rats.
为了阐明具有抗氧化能力的N-乙酰-L-半胱氨酸（NAC）对非诺贝特（FF，一种过氧化物酶体增殖物激活受体（PPAR）α激动剂）所促进的肝癌发生的修饰作用，对雄性F344/N大鼠单次腹腔注射N-二乙基亚硝胺（DEN）作为启动剂，随后给予含3000 ppm FF的饲料16周。在FF处理1周后进行三分之二部分肝切除术。此外，在FF处理2周后进行为期14周的NAC处理。尽管与DEN+FF组相比，DEN+FF+NAC组中肿瘤蛋白p53（Tp53）mRNA的表达水平降低，但在DEN+FF组和DEN+FF+NAC组之间，肝细胞灶性改变的数量和肝细胞增殖活性未观察到显著差异。此外，抗氧化酶测定结果和肝脏中总谷胱甘肽含量的测量显示，DEN+FF组和DEN+FF+NAC组之间无显著差异；尽管在DEN+FF组和DEN+FF+NAC组之间的许多基因中未观察到显著差异，但与DEN+FF组相比，DEN+FF+NAC组中仅谷胱甘肽过氧化物酶2（Gpx2）mRNA增加。本实验条件下的结果表明，NAC对FF诱导的大鼠肝肿瘤促进作用无明显修饰作用。
