Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge

被引:53
作者
Nadler, EP
Dickinson, EC
Beer-Stolz, D
Alber, SM
Watkins, SC
Pratt, DW
Ford, HR
机构
[1] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15261 USA
[3] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15261 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2001年 / 281卷 / 01期
关键词
inducible nitric oxide synthase; endotoxemia; dithiocarbamate; interleukin-6; ornithine carbamoyltransferase;
D O I
10.1152/ajpgi.2001.281.1.G173
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Sustained upregulation of inducible nitric oxide (NO) synthase in the liver after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatocellular injury. We hypothesized that administration of a NO scavenger, NOX, may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats received NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LPS challenge. Hepatocellular injury was assessed using biochemical assays, light, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA was measured by RT-PCR. Tumor necrosis factor (TNF)-alpha protein expression was determined by immunohistochemistry. NOX significantly reduced serum levels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-alpha and IL-6 expression were increased in the livers of saline-treated but not NOX-treated rats. Although there was no difference between groups by light microscopy, TEM revealed obliteration of the space of Disse in saline-treated but not in NOX-treated animals. Electron paramagnetic resonance showed the characteristic mononitrosyl complex in NOX-treated rats. We conclude that NOX reduces hepatocellular injury after endotoxemia. NOX may be useful in the management of hepatic dysfunction secondary to sepsis or other diseases associated with excessive NO production.
引用
收藏
页码:G173 / G181
页数:9
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