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D-galactosamine-induced mouse hepatic apoptosis: possible involvement with tumor necrosis factor, but not with caspase-3 activity.
Biol Pharm Bull 1999; 22(10):1127-30BP

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.No affiliation info availableNo affiliation info availableNo affiliation info available

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 -