Protective Effects And Possible Mechanisms Of Indole-selenium On Acute Liver Injury

Objective To investigate the effects of indole-selenium on carbon tetrachloride-induced chemical liver injury and Bacillus Calmette Guerin (BCG) plus lipopolysaccharide(LPS)-induced immunological liver injury in mice as well as its possible mechanisms. At the same time the pharmacodynamics of indole-selenium was compared with melatonin or selenium of equal dose.Methods The model of chemical liver injury and immunological liver injury in mice was prepared. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST) , nitric oxide(NO) in serum, malondiadehyde(MDA) content, superoxide dismutase(SOD) and glutathione peroxidase(GSH-px) activities in liver homogenate were assayed by spectrophotometry; Tumour necrosis factor-a (TNF-a ) activity was determined by ridio immunoassay method. The level of interleukin-1(lL-1) was assayed by MTT dye reduction. Meanwhile, hepatic pathological examination was observed.Results (1) Indole-selenium (5,10,20mg kg-1) was able to significantly decrease serum transaminase (ALT, AST) levels of chemical liver injury's mice induced by carbon tetrachloride, attenuate the area and extent of necrosis and reduce the infiltration of inflammatory cells. Furthermore, indole-selenium also decreased MDA content and improved the reduced SOD and GSH-px levels in liver homogenate.(2) Indole-selenium (5,10,20mg kg-1) was able to significantly decrease serum transaminase (ALT, AST) levels of immunological liver injury's mice induced by BCG plus LPS, attenuate the area and extent of necrosis and reduce the infiltration of inflammatory cells. Furthermore,indole-selenium also decreased MDA content and improved the reduced SOD and GSH-px levels in liver homogenate. Meanwhile, indole-selenium significantly lowered increased TNF- and NO level in serum and inhibited the production of TNF- a and IL-1 by peritoneal macrophages. (3) Comparing with MT(10 mg kg-1) and Se(0.1 mg kg-1), Indole-selenium ( 10mg kg-1) significantly further changed the serum transaminase levels, MDA production and GSH-px activity while had no difference effect on other index.Conclusion Indole-selenium possesses protective action on chemical liver injury and immunological liver injury in mice, which was related to direct with free radical scavenging, increasing the content of SOD and GSH-px, inhibiting the production of TNF- a and IL-1 by peritoneal macrophages and so on.