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) 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 production of 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, and/or the cytotoxic species derived from .NO.
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
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Chamulitrat
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Spitzer
D000410:Alanine Transaminase / Q000097:blood*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood*; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C004479:pimagedine