The Study On The Protective Effect And Mechanism Of Procyanidin In Acute Liver Injury Induced By Acetaminophen

Acetaminophen (APAP) induced acute liver injury is one of the most common drug-induced acute liver damage in the world. It is a serious threat to human health because of its high incidence and mortality.Currently, N-acetylcysteine (NAC) is the main therapeutic agents in the treatment of liver injury induced by APAP, but the side effects limited its application in clinic. It is necessary to find new drugs.Procyanidin is the most important polyphenols of grape seeds and belongs to bioflavonoids, and exhibits significantly ability to antioxidant and free radical scavenging. Since oxidative stress plays an important role in APAP-induced acute liver injury, it is worthwhile to further discusss whether procyanidin can also protect it by means of oxidative stress.In this research, APAP induced acute liver injury mouse model was constructed to observe the effects of procyanidin on the restoration of liver function, and analyze the levels of related oxidative stress actors, aim to preliminary clarify the protective effect of procyanidin on APAP induced acute liver injury in mice and its potential mechanisms, and provide new theoretical basis for treatment of acute liver damage caused APAP in clinic.Objective:To investigate preliminary protective effect and mechanism of procyanidin in acute liver injury induced by acetaminophen.Methods:1. Construct and identify the mouse model of APAP induced acute liver injury.2.The KM mice were randomly divided into six groups(n=8), including PBS control group, acetaminophen model group, procyanidin control group (100 mg/kg) and procyanidin pre-treatment groups including low-dose 10 mg/kg, medium-dose 50 mg/kg and high-dose group 100 mg/kg.3. Mice serum alanine transaminase (ALT) and asparate aminotransferase (AST) were determined, morphological changes of hepatic tissue were observed by light microscope, and the survival rate of mice were observed by Kaplan-Meier curve.4. Reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) of liver tissue, superoxide dismutase (SOD) were detected by microplate reader.5.The expression of SOD was detected by Western blot.Results:1. APAP induced acute liver injury mouse model was constructed successfully.2.Compared with PBS normal control group,ALT,AST,MDA in APAP model group increased significantly, GSH and GSSG significantly decreased. While compared with APAP model group, ALT,AST,MDA in high-dose of procyanidin group significantly decreased and SOD,GSSG,GSH increased Significantly.Liver tissue in APAP model group was impaired seriously, hepatic cells showed hydropic degeneration, central veins appeared gore,but in high-dose of procyanidin group, lobular had clear structure with slight cell degeneration and insignificant congestion. Mice mortality in APAP model group was 100% and the the survival rate of mice in high-dose of procyanidin group increased significantly.Conclusion:1. APAP induced acute liver injury mouse model was constructed successfully.x 2.Procyanidin has a protective role in acetaminophen-induced acute liver injury, and the preliminary mechanism is related with antioxidative character of drug.