Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat
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- 作者：Ryo Kumamoto (4)
Hirofumi Uto (4)
Kohei Oda (4)
Rie Ibusuki (4)
Shirou Tanoue (4)
Shiho Arima (4)
Seiichi Mawatari (4)
Kotaro Kumagai (4)
Masatsugu Numata (4)
Tsutomu Tamai (4)
Akihiro Moriuchi (4)
Hiroshi Fujita (4)
Makoto Oketani (4)
Akio Ido (4)
Hirohito Tsubouchi (5) - 关键词：Diethylnitrosamine ; Fructose ; Hepatocarcinogenesis ; Nonalcoholic steatohepatitis ; Placental form of glutathione ; S ; transferase
- 刊名：European Journal of Medical Research
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：18
- 期：1
- 全文大小：430 KB
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Hirofumi Uto (4)
Kohei Oda (4)
Rie Ibusuki (4)
Shirou Tanoue (4)
Shiho Arima (4)
Seiichi Mawatari (4)
Kotaro Kumagai (4)
Masatsugu Numata (4)
Tsutomu Tamai (4)
Akihiro Moriuchi (4)
Hiroshi Fujita (4)
Makoto Oketani (4)
Akio Ido (4)
Hirohito Tsubouchi (5)
4. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan
5. Department of HGF Tissue Repair and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan - ISSN：2047-783X
文摘
Background Nonalcoholic fatty liver disease (NAFLD) is a risk for hepatocellular carcinoma (HCC), but the association between a high-fructose diet and HCC is not fully understood. In this study, we investigated whether a high-fructose diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN). Methods Seven-week-old male Sprague–Dawley rats were fed standard chow (controls), a high-fat diet (54% fat), or a high-fructose diet (66% fructose) for 8?weeks. All rats were given DEN at 50?μg/L in drinking water during the same period. Precancerous hepatocytes were detected by immunostaining of the placental form of glutathione-S-transferase (GST-P). The number of GST-P-positive hepatocytes was assessed in liver specimens. Results Serum levels of total cholesterol were similar among the three groups, but serum triglyceride, fasting blood glucose, and insulin levels were higher in the high-fructose group compared to the high-fat group. In contrast, hepatic steatosis was more severe in the high-fat group compared with the high-fructose and control groups, but the incidence of GST-P-positive specimens was significantly higher in the high-fructose group compared to the other two groups. The average number of GST-P-positive hepatocytes in GST-P positive specimens in the high-fructose group was also higher than those in the other two groups. This high prevalence of GST-P-positive hepatocytes was accompanied by higher levels of 8-hydroxydeoxyguanosine in serum and liver tissue. Conclusions These results indicate that dietary fructose, rather than dietary fat, increases the incidence of precancerous hepatocytes induced by administration of DEN via insulin resistance and oxidative stress in rat. Thus, excessive fructose intake may be a potential risk factor for hepatocarcinogenesis.