Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding
✍ Scribed by Shu-Ling Liu; Silvia Degli Esposti; Tony Yao; Anna Mae Diehl; Mark A. Zern
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 901 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
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-KB) activity, and NF-KB 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 CCl, in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of a-tocopherol. Alpha-tocopherol treatment of the mice given the CCl, also reduced the NF-KB binding to levels approaching those found in normal mice. In uitro treatment of a monocyte/macrophage cell line with CCl, led to enhanced NF-KB binding and an increase in tumor necrosis factor-a (TNF-a) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-KB binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with a-tocopherol, a free radical scavenger, also eliminated increased NF-KB binding. It is tempting to speculate that enhanced NF-KB expression caused by free radical productionloxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cy- tokine synthesis. (HEPATOLOGY 1995;22:1474-1481.)
Over the last decade, considerable attention has focused on delineating some of the factors involved in the pathogenesis of liver injury. It appears that several forms of liver injury may be caused at least in part by oxidative stress and the subsequent formation of Abbreviations: ROI, reactive oxygen intermediates; TNF-a, tumor necrosis factor-a; NF-xB, nuclear factor kappa B; IL, interleukin.