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 neutrophils from alcohol-fed animals has been well documented. In this study, electron paramagnetic resonance spectroscopy was used to detect nitrosyl 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 lipopolysaccharide (alc+LPS), increased 3-fold, compared with those from rats on control diet treated with LPS (con+LPS). Electron paramagnetic resonance spectra of whole blood and liver tissues from the alc+LPS-treated group exhibited features characteristic of hemoglobin nitrosyl complexes. Plasma levels of the hepatic ASTs and ALTs from the alc+LPS-treated group were increased 2- to 3-fold, compared with those from the con+LPS-treated group. Inhibition of (NO)-N-. production by aminoguanidine treatment attenuated plasma hepatic enzyme levels in the alc+LPS-treated group. Thus, under the conditions of elevated inflammatory oxidative states caused by chronic alcohol feeding, endotoxin treatment enhanced liver injury as a result of the actions of (NO)-N-., and/or the cytotoxic species derived from (NO)-N-..