Sustained upregulation of inducible nitric oxide (NO) synthase in the liver
after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatoc
ellular injury. We hypothesized that administration of a NO scavenger, NOX,
may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats recei
ved NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LP
S challenge. Hepatocellular injury was assessed using biochemical assays, l
ight, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA w
as measured by RT-PCR. Tumor necrosis factor (TNF)-alpha protein expression
was determined by immunohistochemistry. NOX significantly reduced serum le
vels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-
alpha and IL-6 expression were increased in the livers of saline-treated bu
t 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 sh
owed the characteristic mononitrosyl complex in NOX-treated rats. We conclu
de that NOX reduces hepatocellular injury after endotoxemia. NOX may be use
ful in the management of hepatic dysfunction secondary to sepsis or other d
iseases associated with excessive NO production.