Effect of oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis.
OBJECTIVE
To evaluate the protective effects and mechanism of action of oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in murine liver tissue.


METHODS
Fulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intraperitoneally (ip) in galactosamine (GalN) sensitized mice. Two separate experiments were designed, including saline control group, fulminant hepatitis group and oxymatrine pretreated group (50 mg/kg, intraperitoneally, bid x 3 days). The levels of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5-hour and 7.5-hour after injecting galactosamine/lipopolysaccharide. Mouse liver samples at 5-hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells under transmission electron microscope (TEM). Liver samples at 7.5-hour time point were taken for hematoxylin-eosin (HE) staining and immunohistochemical staining of Fas and its ligand (FasL).


RESULTS
As compared with the fulminant hepatitis group, the levels of serum tumor necrosis factor alpha in mice from the OM pretreated group at 5-hour and 7.5-hour time point were all significantly decreased (P < 0.05 and P < 0.01 respectively). Hepatocyte apoptosis in mice at 5-hour time point was significantly inhibited (P < 0.01). Both the degree of liver injury and the degree of Fas and Fas ligand expression in the OM pretreated group were reduced remarkably (P < 0.01 and 0.05 respectively) when compared with the saline control group.


CONCLUSIONS
Oxymatrine protects mice from fulminant hepatitis induced by GalN/LPS and may block hepatocyte apoptosis and subsequent necrosis through downregulating the production of serum tumor necrosis factor alpha and the expression of Fas and Fas ligand in liver tissue.
Xiang
Xiaoxing
X
Department of Infectious Diseases, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Wang
Guojun
G
Cai
Xiong
X
Li
Yuli
Y
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053222:Fas Ligand Protein; D006520:Hepatitis, Animal / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects; D051379:Mice; D008854:Microscopy, Electron; D011807:Quinolizines; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000187:drug effects; D000093842:Matrines
D000470:Alkaloids; D000998:Antiviral Agents; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011807:Quinolizines; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C505658:Fasl protein, mouse; C037573:oxymatrine; D000093842:Matrines