Maotai ameliorates diethylnitrosamine-initiated hepatocellular carcinoma formation in mice

PLoS One. 2014 Apr 1;9(4):e93599. doi: 10.1371/journal.pone.0093599. eCollection 2014.

Abstract

Consumption of alcohol is closely related to liver disease, such as hepatic fibrosis or even hepatocellular carcinoma (HCC). However, epidemiological and experimental studies indicated that consumption of Maotai, one of the famous liquors in China, exhibits no significant correlation with hepatic fibrosis or cirrhosis as other beverage sources do. This study detected the relationship of Maotai consumption and HCC development in a diethylnitrosamine (DEN)-initiated HCC animal model. DEN was given to mice at a dose of 100 mg/kg, ip, and 50 mg/kg, ip in the following week. Mice were simultaneously given Maotai or an equal amount of ethanol (53%, 5 ml/kg/day, 5 days/week for up to 35 weeks). At 3-week and 35- week of the experiment, serum and livers were collected for biochemical and histopathological examination of liver injury and incidence of HCC. Real-time RT-PCR, immunohistochemistry and Western blotting were used to examine the expression of metallothionein-1/2 (MT-1/2), NF-E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC) and modified subunit (GCLM). We identified tissue damage and dysfunction of liver in ethanol + DEN-treated mice, whereas the extent of injury was reduced in Maotai+ DEN -treated mice. Significant Glypican-3(GPC3) expression and precancerous injury or HCC were seen in approximately 50% of mice with ethanol+ DEN, but barely be seen in Maotai + DEN-treated mice. A higher expression of MT-1/2, Nrf2 and GCLC could be seen in Maotai + DEN-treated mice. Thus, Maotai liquor ameliorates the formation of DEN-induced HCC in mice, and the protection mechanism is possibly related with the activation of anti-oxidation factors, such as MTs, Nrf2 and GCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholic Beverages / adverse effects*
  • Animals
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • China
  • Diethylnitrosamine / toxicity
  • Disease Models, Animal
  • Ethanol / administration & dosage
  • Ethanol / adverse effects
  • Fibrosis / chemically induced
  • Fibrosis / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • NF-E2-Related Factor 2 / biosynthesis

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Diethylnitrosamine
  • Ethanol

Grant support

Supported by a grant from the project 973, Department of Science and Technology, Government of China (2011CB512114). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.