NITRIC-OXIDE AND LIVER-INJURY IN ALCOHOL-FED RATS AFTER LIPOPOLYSACCHARIDE ADMINISTRATION

Earlier studies showed that alcohol-fed animals were more susceptible than controls to injurious effects of endotoxin. Increased superoxide radical production by hepatocyte organelles, Kupffer cells, and neutro phils from alcohol-fed animals has been well documented. In this study , electron paramagnetic resonance spectroscopy was used to detect nitr osyl protein complexes indicating nitric oxide ((NO)-N-.) production. We showed that the concentrations of nitrosyl complexes in whole blood and in liver tissues of alcohol-fed rats treated with lipopolysacchar ide (alc+LPS), increased 3-fold, compared with those from rats on cont rol diet treated with LPS (con+LPS). Electron paramagnetic resonance s pectra of whole blood and liver tissues from the alc+LPS-treated group exhibited features characteristic of hemoglobin nitrosyl complexes. P lasma levels of the hepatic ASTs and ALTs from the alc+LPS-treated gro up were increased 2- to 3-fold, compared with those from the con+LPS-t reated group. Inhibition of (NO)-N-. production by aminoguanidine trea tment attenuated plasma hepatic enzyme levels in the alc+LPS-treated g roup. Thus, under the conditions of elevated inflammatory oxidative st ates caused by chronic alcohol feeding, endotoxin treatment enhanced l iver injury as a result of the actions of (NO)-N-., and/or the cytotox ic species derived from (NO)-N-..