Maotai Ameliorates Diethylnitrosamine-Initiated Hepatocellular Carcinoma Formation in Mice

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.

Melatonin Activates Endoplasmic Reticulum Stress and Apoptosis in Rats with Diethylnitrosamine-Induced Hepatocarcinogenesis

“…Administration of melatonin to DEN-treated animals indicated that the indole was able to reduce hepatocarcinogenic features in HCC-bearing rats, because it ameliorated histology, and reduced changes in serum enzymes and in the expression of GST-P, a protein considered a marker of hepatocarcinogenesis[ 36 ]. These findings are in accordance with results by different authors that also used DEN as a HCC promoter and tested effects of melatonin or other antioxidants, such as resveratrol, maotai or daffron, in rats [ 24 , 37 – 40 ] and mice [ 41 ]. Melatonin also prevented DNA damage in DEN-treated animasl, probably due to its capacity to regulate several key genes involved in DNA repairing pathways, such as CEP152 and N4BP2L2 [ 42 ].…”

Protective Effects ofTotal Glucosides of Paeonyon N-nitrosodiethylamine-induced Hepatocellular Carcinoma in Rats via Down-regulation of Regulatory B Cells

“…Its carcinogenesis process goes through liver injury, liver fibrosis, liver cirrhosis and ultimately develops to HCC. HCC animal model induced by DEN is similar to human HCC and represents a better tool for studying human HCC (Iwasa et al, 2010;Yi et al, 2014). ALT, AST and ALP reflect the degree of liver injury, is more reliable as direct indicator (Yim et al, 2010).…”

Sufentanil Postoperative Analgesia reduce the increase of T helper 17 (Th17) cells and FoxP 3 + regulatory T (Treg) cells in Rat Hepatocellular Carcinoma Surgical Model: A randomised animal study

“…80 Sprague-Dawley rats were intraperitoneal administrated with 0.19% Nnitrosodiethylamine DENA (50 mg kg -1 ) every 3 days for a total of 16 weeks to make HCC models (15) .…”