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, 5days/week for up to 35weeks). 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.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with increasing incidence over the last several decades, and third cancer-related mortality worldwide [1,2]
Hepatocarcinogenesis is considered to be a multi-gene and multi-step disease process and likely involves various pathogenic factors, such as hepatitis B or hepatitis C infection, aflatoxin, and chronic, heavy ethanol consumption [1,3].It is well known that chronic alcohol consumption has long been associated with progressive liver disease toward the development of hepatic cirrhosis and the progression to HCC, especially in developed countries [3,4,5].Prior studies indicated that alcohol synergizes with HBV, HCV and carcinogenic agents, increases the occurrence of liver cirrhosis and HCC[6,7,8,9,10]
Maotai is a traditional Chinese distilled liquor, containing 53% alcohol (v/v), enjoyed by many people all over the world [15].An epidemiological study was performed on workers consuming Maotai longer than ten years during the course of production to taste its quality, the results showed there was no evidence of hepatic fibrosis or cirrhosis in the special crowd, as compared to other beverage sources [15]
Summary
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with increasing incidence over the last several decades, and third cancer-related mortality worldwide [1,2]. Further experimental studies in animals with shortterm oral administration of Maotai or Hep3B cells with exposure of Maotai residue without ethanol showed that Maotai induced remarkable higher metallothioneins and glutathione levels in the liver and produced less liver pathology compared with equal amount of ethanol administration [11,15,16,17,18]. All these results suggest that Maotai could be different from ordinary ethanol and could be less toxic to the liver than the equal alcohol contents from other beverage sources
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