Role of nitric oxide in lipopolysaccharide-induced hepatic injury in D-galactosamine-sensitized mice as an experimental endotoxic shock model

The role of nitric oxide (NO) in lipopolysaccharide (LPS)-induced hepatic i njury was studied in D-galactosamine (n-GalN)-sensitized mice. The inducibl e isoform of NO synthase (iNOS) was immunohistochemically detected on hepat ocytes around blood vessels in livers of mice injected with D-GalN and LPS not on hepatocytes in mice injected with D-GalN or LPS alone, although mRNA for iNOS was found in those mice. Nitrotyrosine (NT) was also found in liv ers of mice injected with D-GalN and LPS. The localization of NT was consis tent with that of iNOS, and the time courses of NT and iNOS expression were almost the same. Expression of iNOS and NT was detected exclusively in the hepatic lesions of mice injected with D-GalN and LPS, Anti-tumor necrosis factor alpha neutralizing antibody inhibited iNOS and NT expression and hep atic injury. The results suggested that NO from iNOS may play a role in LPS -induced hepatic injury on D-GalN-sensitized mice as an experimental endoto xic shock model.