Alterations in the Transcriptional Profile of the Liver Tissue and the Therapeutic Effects of Propolis Extracts in Alcohol-induced Steatosis in Rats

Gene expression Array analysis has been an effective technique for exploring treatment-associated transcriptional changes in tissues. The main goal of this study is to explore the expression changes of transcripts in the liver tissue of rats which were treated with the ethanolic extraction of propolis (EEP) as well as alcohol. We aim to find a subset of genes which responded to the treatment of EEP and may be useful candidate genes in explaining the protective effects of EEP on fatty liver. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that long-term excessive alcohol feeding to rats caused fatty liver, which was characterized by significantly increased plasma levels of alanine aminotransferase and total cholesterol, as well as excessive accumulation of lipids in hepatocytes. After 4-week treatment of EEP, the levels of various blood indices, liver function enzymes and the histopathology of liver were restored to normal. Results from both microarray analysis and quantitative real-time PCR revealed that the hepatic expressions of genes involved in lipogenesis (such as FASN, SCD1, FABP5 and PKLR) were significantly down-regulated by EEP treatment, while the transcriptional expressions of genes involved in the oxidation of fatty acids (such as Acot1 and Acot4) were markedly increased. Our results indicated that concomitant administration of EEP with alcohol helped to restore serological parameters to the normal level and suppress lipid accumulation in the liver tissue. The ability of EEP to alleviate the adverse effects of alcohol on liver may provide a promising natural therapeutic strategy against alcoholic fatty liver.