Protective Effect Of Magnesium Isoglycyrrhizinate On Acute Liver Injury Induced By Cyclamate In Mice

Objective:To investigate the preventive effect of magnesium isoglycyrrhizinate injection on cyclamate-induced acute liver injury in mice and its possible mechanism.Method:The mice models of acute liver injuries induced by intraperitoneal injection of cyclamate were established.The experimental mice were randomly divided into normal group,model group,high dose magnesium isoglycyrrhizate group,medium dose magnesium isoglycyrrhizinate,low dose magnesium isoglycyrrhizinate group and polyene phosphatidylcholine positive control group.Except the normal group,the other groups of mice were continuously given cyclamate for 14 days,while the mice of different groups of magnesium isoglycyrrhizinate were injected intraperitoneally with different doses of magnesium isoglycyrrhizinate.The mice in the polyene phosphatidylcholine positive control group was given polyene phosphatidylcholine.At the end of the 14 th day,the indicators of each group were observed,including body weight,liver index;alanine aminotransferase,aspartate aminotransferase,glutathione,glutathione peroxidase,malondialdehyde,nitric oxide.What is more,we need to observe the HE staining of liver tissue and the ultrastructural changes of hepatocytes under electron microscope.Serum and liver tissue tumor necrosis factor-? was detected by ELISA.Transforming growth factor-?1 and its expression were detected by immunohistochemistry.Results:(1)After 14 days,liver function was significantly increased in the liver of the model group.Hepatocyte HE staining showed inflammatory cell infiltration,a large number of balloon-like changes and successful modeling;(2)Being treated by different drugs for 14 days,the body weight and liver index of the mice in each model group decreased significantly.On the contrary,the body weight and liver index of the mice treated with the drug increased(P<0.05 compared with the model group),especially the high dose magnesium isoglycyrrhizate group(P<0.05 compared with other drug intervention groups);(3)Alanine aminotransferase,aspartate aminotransferase,glutathione,glutathione peroxidase,malondialdehyde,and nitric oxide in the model groups significantly increased(P<0.05 compared with the normal group),while drug intervention groups are on the contrary.(P<0.05 compared withmodel group),with magnesium glycyrrhizinate high dose group decreasing the most(P<0.05 compared with others in the drug intervention group;(4)The liver tissue of the normal group was normal,while the liver tissue of the model group showed different degrees of hepatocyte necrosis,infiltration of inflammatory cells,and the liver tissue pathology of the mice in drug intervention groups improved.(5)The TNF-? level of the model group significantly increased(P<0.05 compared with the normal group),and the level of TNF-? decreased in each drug group(P<0.05 compared with the model group);(6)The expression of TGF-?1 in the model group increased(P<0.05 compared with the normal group)and the expression of TGF-?1 in drug intervention group(P<0.05 compared with the model group),but the difference between the groups were not significant.Conclusion:1.The mechanism of acute liver injury induced by cyclamate may be related to oxidative stress,TNF-? and TGF-?1mediated inflammation;2.Magnesium glycyrrhizinate injection has a protective effect on acute liver injury induced by sodium cyclamate in mice,whose one of the possible mechanisms may be by reducing oxidative stress and inflammation.