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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2010, Vol. 15 ›› Issue (11): 1229-1233.

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Effect of the caspase selective inhibitor F1013 on hepatocyte apoptosis in rats with fulminant hepatic failure

DENG Li-juan1, LI Zhan-jun1, LUO Ying2, FAN Hui-hong1   

  1. 1National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050,China;
    2Shanghai Genomics Inc.,Shanghai 201203,China
  • Received:2010-10-08 Revised:2010-11-20 Online:2010-11-26 Published:2020-09-16

Abstract: AIM: To observe the protective effect of F1013 on fulminant hepatic failure (FHF) induced by lipopolysaccharide(LPS) plus D-galactosamine (D-GalN) in rats and to investigate its mechanism of action. METHODS: The rat model of FHF was induced by intra-peritoneal injection of LPS plus D-GalN. The contents of ALT, AST and total bilirubin (TBIL) were examined by an entire automatic biochemistry, the hepatic pathological changes were observed with hematoxylin-eosin(HE) stain , and the hepatocyte apoptosis was detected with FCM and TUNEL. RESULTS: Compared with the control group,serum levels of ALT,AST and TBIL and the expression of hepatocyte apoptosis in rats of the model group were significantly elevated (P<0.01).Compared with the model group,5,2.5,1.25 mg/kg F1013 treatment groups could effectively improve the hepatic tissue injury, reduce serum levels of ALT and AST and the expression of hepatocyte apoptosis (P<0.01 or P<0.05) , 5 mg/kg F1013 treatment group reduce serum levels of TBIL(P<0.01). CONCLUSION: It is shown that F1013 has a promising protective effect on rats with FHF caused by LPS plus D-GaIN, and its mechanism is probably related to the inhibition of liver tissue cell apoptosis.

Key words: F1013 , Fulminant hepatic failure , Apoptosis

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