Protective Effect And Mechanism Of Liuyuexue Compound (LYXC) Against Acute And Chronic Chemical Liver Injuries

Objective: (1) To observe the inhibitive effect of LYXC against HBsAg and HBeAg in vitro. (2) To study protective effect and involved possible mechanisms of LYXC against carbon tetrachloride (CCl4)-, Acetaminophen (AP)- and D-Galactosamine (D-Gal)-induced acute liver injuries in mice and CCl4-induced liver fibrosis in rats. Methods: (1) Inhibiting effect of LYXC against HBsAg and HBeAg in vitro: LYXC, at different concentrations was mixed with the serum containing HBsAg or HBeAg for 0 (at once), 4, 8, 16h and the inhibition of LYXC on HBsAg and HBeAg in vitro was observed by the measurement of HBsAg and HBeAg levels using ELISA. (2) Heparprotection of LYXC against chemical liver injuries: The models of CCl4-, AP-, D-Gal-induced acute liver injuries in mice and CCl4-induced liver fibrosis in rats were used to study the protecteive effect and involved possible mechanisms of LYXC on liver injury. (3) Effects of LYXC on hepatic microsomal enzymes, GSH, GSH-PX and Ca2+-ATPase in untreated mice. Results: (1) LYXC could significantly decrease the titres of HBsAg or HBeAg when the concentrations of LYXC were 12mg/ml or greater at 0, 4, 8, 16h after the treatment with LYXC in vitro (P<0.01). 6mg/ml of LYXC could also significantly decrease the titres of HBsAg 8h and titres of HBeAg 4h after the same treatment. (2) LYXC of low, middle and high doses could significantly decrease the elevations of serum ALT and AST activities in acute liver injuries induced by CCl4-, AP- and D-Gal in mice and in chronic liver injury induced by CCl4 in rats (P<0.01), lessened the pathologyical damage of hepatocytes, and increased the contents of hepatic microsomal Cyt.b5 and Cyt.P450 in liver (P<0.01). In liver fibrosis induced by CCl4, LYXC could markedly increase the activities of hepatic microsomal aniline hydroxylase, aminopyrine-N-demethylase and SOD, inhibit the formation of malondialdehyde (MDA) in liver (P<0.01).LYXC could also obviously decrease the content elevations of laminin (LN), hyaluronic acid (HA), procoliagen type â…¢ (PCâ…¢), type â…£ collagen (â…£C) and hydroxyproline (HYP) in liver, increase the contents of total protain (TP) and albumin (ALB) (P<0.01) in the serum (P<0.01). The results also showed that there was a certain dose-effect relationships among low, middle and high doses of LYXC. (3) The contents of Cyt.P450 and Cyt.b5 and the activities hepatic microsomal aniline hydroxylase, aminopyrine N-demethylase, GSH, GSH-PX and Ca2+-ATPase were significantly increased by the treatment with this drug. Conclusions: (1) HBsAg and HBeAg was markedly inhibited by the treatment with LYXC in vitro. (2) LYXC has significant protective effects on the acute liver injuries induced by CCl4, AP and D-Gal in mice and on the liver fibrosis caused by CCl4 in rats. (3) Hepatoprotection of LYXC maybe result from the induction of hepatic microsomal drug-metabolizing enzymes, the increase in the content of GSH and the activities of GSH-PX and Ca2+-ATPase, the inhibition of Lipid peroxidation, and the clearance of free radical.