2008Archivum histologicum japonicumOpen access

The inhibition of apoptosis by glycyrrhizin in hepatic injury induced by injection of lipopolysaccharide / D-galactosamine in mice

Tadayuki Ikeda, Kazuki Abe, Noriyuki Kuroda, Yujiro Kida, Hideo Inoue, Kenjiro Wake, Mitsuhiko Morito, Tetsuji Sato

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Abstract

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.

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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.

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Available abstract

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.

Key concepts: Glycyrrhizin, TUNEL assay, Apoptosis, Lipopolysaccharide, Galactosamine, Liver injury, Pharmacology, Transaminase

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