Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide- induced liver injury

Quanbo Xiong, Kouji Hase, Yasuhiro Tezuka, Tsuneo Namba, Shigetoshi Kadota

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 μg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-α (TNF-α) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-α, but it partially prevented in vitro TNF-α (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 μM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-α-dependent hepatic apoptosis.

Original languageEnglish
Pages (from-to)421-430
Number of pages10
JournalLife Sciences
Volume65
Issue number4
DOIs
Publication statusPublished - 1999 Jun 18
Externally publishedYes

Fingerprint

Galactosamine
Liver
Lipopolysaccharides
Apoptosis
Wounds and Injuries
Tumor Necrosis Factor-alpha
Hepatitis
Macrophages
Liver Failure
DNA Fragmentation
Cell death
acteoside
Hepatocytes
Cell Death
Antioxidants
Oxygen
DNA
Serum

Keywords

  • Acteoside
  • Apoptosis
  • D-galactosamine
  • Lipopolysaccharide
  • Necrosis
  • Reactive oxygen intermediates
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pharmacology

Cite this

Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide- induced liver injury. / Xiong, Quanbo; Hase, Kouji; Tezuka, Yasuhiro; Namba, Tsuneo; Kadota, Shigetoshi.

In: Life Sciences, Vol. 65, No. 4, 18.06.1999, p. 421-430.

Research output: Contribution to journalArticle

Xiong, Quanbo ; Hase, Kouji ; Tezuka, Yasuhiro ; Namba, Tsuneo ; Kadota, Shigetoshi. / Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide- induced liver injury. In: Life Sciences. 1999 ; Vol. 65, No. 4. pp. 421-430.
@article{a9cc254493af47a2a4e83e85de2ac019,
title = "Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide- induced liver injury",
abstract = "We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 μg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-α (TNF-α) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-α, but it partially prevented in vitro TNF-α (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 μM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-α-dependent hepatic apoptosis.",
keywords = "Acteoside, Apoptosis, D-galactosamine, Lipopolysaccharide, Necrosis, Reactive oxygen intermediates, Tumor necrosis factor-α",
author = "Quanbo Xiong and Kouji Hase and Yasuhiro Tezuka and Tsuneo Namba and Shigetoshi Kadota",
year = "1999",
month = "6",
day = "18",
doi = "10.1016/S0024-3205(99)00263-5",
language = "English",
volume = "65",
pages = "421--430",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Acteoside inhibits apoptosis in D-Galactosamine and lipopolysaccharide- induced liver injury

AU - Xiong, Quanbo

AU - Hase, Kouji

AU - Tezuka, Yasuhiro

AU - Namba, Tsuneo

AU - Kadota, Shigetoshi

PY - 1999/6/18

Y1 - 1999/6/18

N2 - We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 μg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-α (TNF-α) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-α, but it partially prevented in vitro TNF-α (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 μM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-α-dependent hepatic apoptosis.

AB - We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 μg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-α (TNF-α) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-α, but it partially prevented in vitro TNF-α (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 μM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-α-dependent hepatic apoptosis.

KW - Acteoside

KW - Apoptosis

KW - D-galactosamine

KW - Lipopolysaccharide

KW - Necrosis

KW - Reactive oxygen intermediates

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=0033580770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033580770&partnerID=8YFLogxK

U2 - 10.1016/S0024-3205(99)00263-5

DO - 10.1016/S0024-3205(99)00263-5

M3 - Article

C2 - 10421428

AN - SCOPUS:0033580770

VL - 65

SP - 421

EP - 430

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 4

ER -