Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge

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.