title: Nitric oxide production in experimental alcoholic liver disease in the rat: role in protection from injury.
abstract: OBJECTIVE
  Regulation of blood flow and oxygen supply are important pathogenetic factors in alcoholic liver disease. Because nitric oxide may have an important role, its effects on alcoholic liver injury were investigated.
  
  
  METHODS
  Rats were fed ethanol intragastrically with either saturated fat or corn oil. Spontaneous production of NO by liver nonparenchymal cells was compared in the two dietary groups. Two additional groups of rats fed corn oil and ethanol were treated with either an NO inhibitor (L-NAME) or supplemented with L-arginine. Liver pathology and plasma NO production were evaluated.
  
  
  RESULTS
  In the corn oil and ethanol group, a progressive decrease in liver nonparenchymal cell NO production and increased plasma NO levels were associated with liver injury. Reduced nicotinamide adenine dinucleotide phosphate diaphorase staining showed increased centrilobular staining of hepatocytes in the corn oil and ethanol group and L-NAME-treated group. Moreover, L-NAME increased the severity, whereas L-arginine supplementation completely prevented liver injury. In the saturated fat and ethanol group, in which there was no liver injury, the levels of NO2- in nonparenchymal supernatant were 5-10-fold higher than in the corn oil and ethanol group.
  
  
  CONCLUSIONS
  Decreased NO production by nonparenchymal cells may contribute to liver injury in ethanol-fed rats, and the compensatory increase in hepatocyte NO production may contribute to centrilobular liver injury.
authors.affiliation: Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Nanji
authors.forename: S S
authors.initials: SS
authors.lastname: Greenberg
authors.forename: S R
authors.initials: SR
authors.lastname: Tahan
authors.forename: F
authors.initials: F
authors.lastname: Fogt
authors.forename: J
authors.initials: J
authors.lastname: Loscalzo
authors.forename: S M
authors.initials: SM
authors.lastname: Sadrzadeh
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: J S
authors.initials: JS
authors.lastname: Stamler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester