Effect Of Magnesium Isoglycyrrhizinate On Liver Injury Model And Its Mechanism

Background: Magnesium Isoglycyrrhizinate is regarded as a new hepatoprotective drug and used widely in the treatment of chronic viral hepatitis patients in China. The protection of Magnesium Isoglycyrrhizinate against CCl4, D-galactosamine-induced liver injury, is closely related to its elimination of free radicals and inhibition of oxidative stress. However, there is short of the report about Magnesium Isoglycyrrhizinate protecting immunological liver injury. Therefore, the aim of the present study was to investigate the protective effect of Magnesium Isoglycyrrhizinate on ConA-induced immunological liver injury in mice and its mechanism.Objective: To investigate the effect of Magnesium Isoglycyrrhizinate on Con A-induced immunological liver injury in ICR mice.Methods: 48 ICR mice were randomly divided into normal group,model group,treatment groups at different dosage of Magnesium Isoglycyrrhizinate (12.5,25,50 mg/kg) and Dexamethasone group. Magnesium Isoglycyrrhizinate was injected for 5 d by intraperitoneal injection, and Con A was injected via tail vein on the 5th day to establish immunological liver injury model. 8 h after the ConA injection, serum ALT, AST and TNF-α, IFN-γlevels were determined. And the levels of MPO, MDA, NP and SOD in liver homogenate were also determined. Liver lesions were observed by light microscope.Results:The levels of ALT, AST,TNF-α,IFN-γin Serum,and the content of MPO, MDA, NP in liver homogenate and liver lesions were increased by Con A injection,while SOD activity was reduced. And intraperitoneal injection of Magnesium Isoglycyrrhizinate can markedly reduce the levels of ALT, AST,TNF-α,IFN-γin serum,and the content of MPO,MDA,NP in liver homogenate and liver lesions in Con A-induced mice(P﹤0.05) and increase SOD activity(P﹤0.05). And also lessen liver lesions in Con A-induced mice.Conclusions: Magnesium Isoglycyrrhizinate potects against Con A-induced liver injury effectively, its mechanism may be associated with the immunoregulation and antioxidative action. Objective: To investigate the effect of Magnesium Isoglycyrrhizinate on acetaminophen -induced liver injury in rats.Methods: 56 SD rats were randomly divided into normal group, model group, treatment groups at different dosage of Magnesium Isoglycyrrhizinate(30,15,7.5 mg/kg),Cyclosporin A(15mg/Kg) and N-acetylcysteine ( 40mg/Kg ) group. Magnesium Isoglycyrrhizinate was intraperitoneal injected for 5d, and acetaminophen(2000mg/Kg) was intragastriced administration on d5 to establish acetaminophen-induced liver injury model. 24 h after the acetaminophen injection, analyze serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin(TBil)values, and detect the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of malonicdialdehyde (MDA), glutathion (GSH) and myeloperoxidase(MPO) in liver tissue were also determined. Detect the activity of succinodehydrogenase (SDH) and adenosine triphosphatase (ATPase) in liver mitochondria, and detect the number of TUNEL, Cytc, Bcl-2 and Bax.RESULTS: Magnesium Isoglycyrrhizinate could significantly prevent liver toxicity in the model of liver damage. It decreased the high levels of ALT, AST and TBil in serum induced by the administration of acetaminophen, reduced the cellular damage of liver markedly, and appeared to be even more potent than Cyclosporin A and N-acetylcysteine. In groups treated with different doses of Magnesium Isoglycyrrhizinate, compared to the model group, the content of MDA and MPO in liver tissue decreased evidently, whereas the content of SOD, GSH and GSH-Px increased, and the difference was statistically significant. Further, in the study of acetaminophen model, Magnesium Isoglycyrrhizinate inhibited acetaminophen-induced liver toxicity in rat, enhanced the activity of NADH, ATPase, SDH and the expression of Bcl-2, and decreased the number of TUNEL and the expression of Cytc, Bax.Conclusion: Magnesium Isoglycyrrhizinate can evidently relieve hepatocyte injuries induced by acetaminophen, help scavenge free radicals and enhance the activity of ATPase and SDH in mitochondria, thereby modulating the balance of liver energy metabolism, which might be part of the mechanisms of hepatoprotective effects of Magnesium Isoglycyrrhizinate.