D-Galactosamine-Induced Mouse Hepatic Apoptosis : Possible Involvement with Tumor Necrosis Factor, but not with Caspase-3-Activity

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概要

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• We investigated whether tumor necrosis factor (TNF) and caspase-3 activity are involved in the induction of hepatocellular apoptosis in D-galactosamine (D-GalN)-induced hepatotoxicity in mice. Acute hepatotoxicity was induced by the intraperitoneal injection of D-GalN into female BALB/c mice. D-GalN (0.75-3.0 g/kg) increased the serum blutamate pyruvate transaminase (s-GPT) activity and the percentage of liver DNA fragmentation, an indicator of hepatotoxicity, after 48 h, in a dose-dependent manner. Furthermore, after D-GalN (3.0 g/kg) administration, increased liver DNA fragmentation was detected biochemically at 24 h, then increased s-GPT activity accompanied by increased liver DNA fragmentation was observed after 48 h. The serum TNF (s-TNF) level and the TNF mRNA expression in the liver after D-GalN (3.0 g/kg, i.p.) administration were examined by an ELISA kit and reverse transcription polymerase chain reaction (RT-PCR), respectively, to investigate the relation between the s-GPT activity and liver DNA fragmentation. The s-TNF level and TNF mRNA expression in the liver after D-GalN (3.0 g/kg) administration were detected earlier than liver DNA fragmentation, then increased with time. However, there was almost no association of caspase-3 activity with the increase in liver DNA fragmentation. Increases in the s-TNF level, TNF mRNA expression and the percentage of DNA fragmentation in the liver and s-GPT activity were inhibited by dexamethasone (Dex; 0.4-2.5 mg/kg, i.p.) in a dose-dependent manner. Based on these findings, it was considered that the intracellular apoptosis signal in D-GalN-induced hepatotoxicity in mice did not depend on caspase-3 activity, and that other signals mediated by TNF may be involved.

• 公益社団法人日本薬学会の論文
• 1999-10-15

著者

• Omata Takeshi

  Department Of Applied Research Central Laboratories Zeria Pharmaceutical Co. Ltd.

• SEGAWA Yoshihide

  Department of Pharmacology, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.,

• SEGAWA Yoshihide

  Zeria Pharmaceutical Co., Ltd.

• ITOKAZU Yoshihiko

  Zeria Pharmaceutical Co., Ltd.

• INOUE Naonori

  Zeria Pharmaceutical Co., Ltd.

• Inoue N

  Zeria Pharmaceutical Co. Ltd.

• ITOKAZU Yoshihiko

  Department of Applied Research, Central Laboratories, Zeria Pharmaceutical Co., Ltd.,

• INOUE Naonori

  Department of Applied Research, Central Laboratories, Zeria Pharmaceutical Co., Ltd.,

• Segawa Y

  Zeria Pharmaceutical Co. Ltd.

• Segawa Yoshihide

  Department Of Pharmacology Central Research Laboratories Zeria Pharmaceutical Co. Ltd.

• Itokazu Y

  Zeria Pharmaceutical Co. Ltd.

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