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The Protective Effect of Soybean Isofalvone Against Hepatotoxicity and Its Mechanism

Author: LiTian
Tutor: QuanJiShu
School: Yanbian University
Course: Biochemistry and Molecular Biology
Keywords: soy isoflavones CCl4 GalN LPS liver injury
CLC: R285.5
Type: Master's thesis
Year: 2010
Downloads: 130
Quote: 1
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Abstract


Objective:The purpose of this study was to investigate the protective effect of soybean isofalvone against hepatotoxicity and its mechanism.Method:1. Fifty male Kunming mice were randomly divided into 5 groups of 10 each, that is, the control group, model group, bifendate group, low and high dose soy isoflavone groups. soy isoflavone was administered once daily for a period of 7 days. One hour after the final treatment, the mice were treated intraperitoneally (i.p.) with CCl4. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver superoxide dismutase (SOD), catalase(CAT) and malondialdehyde (MDA) was measured with the colormetric methed, and inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) expression in liver was measured with the western blot method.2. Fifty male Kunming mice were randomly divided into 5 groups of 10 each, that is, the control group, model group, silymarin group, low and high dose soy isoflavone groups. soy isoflavone was administered once daily for a period of 7 days. One hour after the final treatment, the mice were treated intraperitoneally (i.p.) with D-galactosamine (GalN) and lipopolysaccharide (LPS).The serum ALT, AST and liver Caspase-3 and 8 activities were measured with the colormetric methed, and liver tumor necrosis factor-a (TNF-a) was measured with ELISA methed.Results:1.CCl4-induced hepatotoxicity was manifested by increased levels of serum ALT and AST, liver MDA, and by decreased activites of heaptic SOD and CAT. CCl4 challenge also resulted in elevated iNOS and COX-2 contents in liver. Pretreatment of mice with soybean isofalvone reversed these altered parameters induced by CCl4. Interestingly, soybean isofalvone markedly upregulated hepatic HO-1 protein expression in CCl4-treated mice, which might provide an antioxidative activity in liver. The effect of soybean isofalvone was further demonstrated by histopathological examination of liver sections.2. GalN/LPS-induced hepatotoxicity was manifested by increased levels of serum transaminases and TNF-a, and by decreased caspase-3 activity. There is no significant difference in caspase-8 activity.Conclusion:soybean isofalvone plays a protective role in acute liver injury, and its protective effect may be due to reduced lipid peroxidation and elevated antioxidative defense potential, suppressed inflammatory responses, and elevated HO-1 protein expression, combined with inhibited hepatic apoptosis.

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