title: No Modifying Effect of Antioxidant N-Acetyl-L-Cysteine on Fenofibrate-induced Hepatocarcinogenesis in Rats.
abstract: 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.
authors.forename: Jihei
authors.initials: J
authors.lastname: Nishimura
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Dewa
authors.forename: Meilan
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authors.lastname: Jin
authors.forename: Yukie
authors.initials: Y
authors.lastname: Saegusa
authors.forename: Masaomi
authors.initials: M
authors.lastname: Kawai
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kemmochi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Harada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Itoh
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shima
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Mitsumori