Study on the Mechanism for the Beneficial Effects of Soy Protein on Alcoholic Liver Diseases

Alcoholic liver disease (ALD) is the common consequence of prolong alcohol intake. The metabolism of alcohol generates free radicals which lead to increase oxidative stress, abnormal lipid metabolism, hepatic fat accumulation, destroy the integrity of intestinal barrier, increases intestinal permeability, and may further cause liver inflammation. Previous studies indicated that soy protein may be beneficial in improving lipid profile, reducing oxidative stress, inflammation, and intestinal injury. Therefore, the aim of this study is to investigate the effects of soy protein consumption on ALD. First, we use rat primary hepatocyte to investigate the effects of different isoflavones, genistein and daidzein during ethanol treatment. Analysis of lipid content, antioxidative enzyme activity, TNF-α, CYP2E1and PPAR-α (peroxisome proliferator activated receptor-α) protein expression will be done 9, 12, 24 and 48 hours after treatment. In the second part of the study, we plan to investigate the effect of soy protein on ALD in vivo. Rats will be fed with 20% alcohol to induce ALD and divided into 4 groups: the C group (control), the N group (20% ehtanol) and the E group (20% ethanol + soy protein). After 30 weeks, blood and liver will be collected for the analysis of lipids, antioxidative enzyme activities and cytokines concentrations. Liver sample will also be used for analysis of CYP2E1 and PPAR-α protein expression. In the third part of the study, we use NSAIDs to increase intestinal permeability to investigate whether soy protein consumption can ameliorate indomethacin-induced intestinal injury and improve tissue inflammation. Rats will be fed with control or soy protein diet, and injected with indomethacin at the 2nd week. We will evaluate intestinal permeability at the 0, 2, 3 and 4 week. Blood, liver and intestine will be collected for the determination of cytokines concentrations and pathohistological analysis.