Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding

Shu Ling Liu, Silvia Degli Esposti, Tony Yao, Anna Mae Diehl, Mark A Zern

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-κB) activity, and NF-κB activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of α-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-κB binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-κB binding and an increase in tumor necrosis factor-α (TNF-α) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-κB binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with α-tocopherol, a free radical scavenger, also eliminated increased NF-κB binding. It is tempting to speculate that enhanced NF-κB expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.

Original languageEnglish (US)
Pages (from-to)1474-1481
Number of pages8
JournalHepatology
Volume22
Issue number5
DOIs
StatePublished - 1995
Externally publishedYes

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NF-kappa B
Vitamin E
Liver
Wounds and Injuries
Oxidative Stress
Tocopherols
Cytokines
Oxygen
Free Radical Scavengers
alpha-Tocopherol
Distance Counseling
Inhibition (Psychology)
Emulsions
Intraperitoneal Injections
Hepatitis
Free Radicals
Monocytes
Tumor Necrosis Factor-alpha
Macrophages
Cell Line

ASJC Scopus subject areas

  • Hepatology

Cite this

Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding. / Liu, Shu Ling; Degli Esposti, Silvia; Yao, Tony; Diehl, Anna Mae; Zern, Mark A.

In: Hepatology, Vol. 22, No. 5, 1995, p. 1474-1481.

Research output: Contribution to journalArticle

Liu, Shu Ling ; Degli Esposti, Silvia ; Yao, Tony ; Diehl, Anna Mae ; Zern, Mark A. / Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding. In: Hepatology. 1995 ; Vol. 22, No. 5. pp. 1474-1481.
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