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D-galactosamine-induced mouse hepatic apoptosis: possible involvement with tumor necrosis factor, but not with caspase-3 activity.

Abstract

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 glutamate 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.

Authors+Show Affiliations

,

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

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Source

Biological & pharmaceutical bulletin 22:10 1999 Oct pg 1127-30

MeSH

Animals
Anti-Inflammatory Agents
Apoptosis
Caspase 3
Caspases
DNA Fragmentation
Dexamethasone
Drug Interactions
Female
Galactosamine
Interferon-gamma
Liver
Mice
Mice, Inbred BALB C
RNA, Messenger
Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10549870

Citation

Itokazu, Y, et al. "D-galactosamine-induced Mouse Hepatic Apoptosis: Possible Involvement With Tumor Necrosis Factor, but Not With Caspase-3 Activity." Biological & Pharmaceutical Bulletin, vol. 22, no. 10, 1999, pp. 1127-30.
Itokazu Y, Segawa Y, Inoue N, et al. D-galactosamine-induced mouse hepatic apoptosis: possible involvement with tumor necrosis factor, but not with caspase-3 activity. Biol Pharm Bull. 1999;22(10):1127-30.
Itokazu, Y., Segawa, Y., Inoue, N., & Omata, T. (1999). D-galactosamine-induced mouse hepatic apoptosis: possible involvement with tumor necrosis factor, but not with caspase-3 activity. Biological & Pharmaceutical Bulletin, 22(10), pp. 1127-30.
Itokazu Y, et al. D-galactosamine-induced Mouse Hepatic Apoptosis: Possible Involvement With Tumor Necrosis Factor, but Not With Caspase-3 Activity. Biol Pharm Bull. 1999;22(10):1127-30. PubMed PMID: 10549870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - D-galactosamine-induced mouse hepatic apoptosis: possible involvement with tumor necrosis factor, but not with caspase-3 activity. AU - Itokazu,Y, AU - Segawa,Y, AU - Inoue,N, AU - Omata,T, PY - 1999/11/5/pubmed PY - 1999/11/5/medline PY - 1999/11/5/entrez SP - 1127 EP - 30 JF - Biological & pharmaceutical bulletin JO - Biol. Pharm. Bull. VL - 22 IS - 10 N2 - 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 glutamate 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. SN - 0918-6158 UR - https://www.unboundmedicine.com/medline/citation/10549870/D_galactosamine_induced_mouse_hepatic_apoptosis:_possible_involvement_with_tumor_necrosis_factor_but_not_with_caspase_3_activity_ DB - PRIME DP - Unbound Medicine ER -