The inhibition of apoptosis by glycyrrhizin in hepatic injury induced by injection of lipopolysaccharide / D-galactosamine in mice.
The inhibition of apoptosis by glycyrrhizin (GL) in hepatic injury induced by injection of lipopolysaccharide (LPS)/D-galactosamine (D-GalN) was examined in the present study. Morphological and biochemical analyses of LPS/D-GalN-induced mouse liver injury revealed that apoptosis occurred exclusively in injured hepatocytes of the centrilobular area. The degree of hepatic injury was associated with a substantial number of hepatocytes undergoing apoptosis. Transaminase levels were significantly increased at 6 to 8 h after the injection of LPS/D-GalN compared with controls. GL inhibited the elevation of serum transaminase levels when it was given to mice at 30 min before the administration of LPS/D-GalN. Morphological analyses using the TUNEL-method showed GL significantly reduced the number of TUNEL-labeled cells in acute hepatitis induced with LPS/D-GalN-treatment. Cells from the pericentral hepatic injury region were dissected out using a microdissection-method, and the DNA-ladder was clearly documented. Furthermore, results obtained through the TUNEL-method were confirmed with an oligonucleosome-bound DNA ELISA. From the current results, it seems reasonable to conclude that the protective role of GL in LPS/D-GalN-induced liver injury is performed through the inhibition of hepatic apoptosis.
Ikeda
Tadayuki
T
Department of Anatomy II, School of Dental Medicine, Tsurumi University, Yokohama, Japan.
Abe
Kazuki
K
Kuroda
Noriyuki
N
Kida
Yujiro
Y
Inoue
Hideo
H
Wake
Kenjiro
K
Morito
Mitsuhiko
M
Sato
Tetsuji
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D005688:Galactosamine / Q000008:administration & dosage; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D019695:Glycyrrhizic Acid; D005688:Galactosamine; D020169:Caspases