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5TH INTERNATIONAL CONFERENCE ON METALLOTHIONEIN SYMPOSIUM PAPERS

Differential Effects Between Maotai and Ethanol on Hepatic Gene Expression in Mice: Possible Role of Metallothionein and Heme Oxygenase-1 Induction by Maotai

Jie Liu^*, Min-Liang Cheng^,1, Jin-Zheng Shi, Qin Yang, Jun Wu, Cheng-Xiu Li and Michael P. Waalkes^*

^* Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Research Triangle Park, North Carolina; Guiyang Medical College Hospital, Guizhou, China; and Guiyang Traditional Medical College, Guizhou, China

To whom requests for reprints should be addressed at ¹ Guiyang Medical College Hospital, Guiyang, Guizhou 550004, China. E-mail: Chengml{at}21cn.com and Liu6{at}niehs.nih.gov

Abstract

Alcohol is a risk factor for liver fibrosis and hepatocellular carcinoma. On the other hand, light alcoholic beverage consumption is believed to be beneficial because of the effects of both alcohol and nonalcoholic components of the beverage. Maotai is a commonly consumed beverage in China containing 53% alcohol. Epidemiological and experimental studies show that Maotai is less toxic to the liver than ethanol alone. To examine the differential effects of Maotai and ethanol, a low dose of Maotai or an equal amount of ethanol (53%, v/v in water, 5 ml/kg) were given to male mice daily for 1 week, and hepatic RNA was extracted for microarray analysis. Approximately 10% of genes on the liver-selective custom array (588 genes) were altered following Maotai or ethanol administration, but Maotai treated livers had fewer alterations compared with ethanol alone. Real-time reverse transcription–polymerase chain reaction confirmed and extended microarray results on selected genes. An induction of metallothionein and heme oxygenase-1 occurred with Maotai, which could not be explained by alcohol consumption alone, whereas the attenuation of ethanol responsive genes such as quinone dehydrogenase, DNA-ligase 1, IGFBP1, and IL-1ß suggests less liver injury occurred with Maotai. The expression of genes related to liver fibrosis, such as cytokeratin-18, was slightly increased by the high dose of ethanol, but was unchanged in the Maotai group. In summary, gene expression analysis indicates that Maotai induces a different response than ethanol alone. The dramatic induction of metallothionein and heme oxygenase-1 with Maotai could be important adaptive responses to reduce alcoholic liver injury.

Key Words: ethanol • Maotai • gene expression • metallothionein • heme oxygenase-1 • liver

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