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Título: Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat
Autores: Kumamoto, Ryo
Uto, Hirofumi
Oda, Kohei
Ibusuki, Rie
Tanoue, Shirou
Arima, Shiho
Mawatari, Seiichi
Kumagai, Kotaro
Numata, Masatsugu
Tamai, Tsutomu
Moriuchi, Akihiro
Fujita, Hiroshi
Oketani, Makoto
Ido, Akio
Tsubouchi, Hirohito
Fecha: 2013-12-09
Publicador: BioMed Central Ltd.
Fuente: Ver documento
Tipo: Research
Tema: Diethylnitrosamine, Fructose, Hepatocarcinogenesis, Nonalcoholic steatohepatitis, Placental form of glutathione-S-transferase
Descripción: Abstract 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.
Idioma: Inglés