title: Does upregulation of inducible nitric oxide synthase play a role in hepatic injury?
abstract: Lipopolysaccharide (LPS) and gut ischemia/reperfusion (I/R) injury cause reversible liver injury. Because nitric oxide (NO) can have both beneficial and deleterious effects in the gastrointestinal tract, and because the role of NO in gut I/R-induced hepatic injury is unknown, this study examined its role in LPS and gut I/R-induced hepatic injury in the rat. Both LPS and gut I/R caused a similar increase in serum hepatocellular enzymes. LPS but not gut I/R caused a significant increase in upregulation of hepatic inducible NO synthase (iNOS) according to quantitative real-time RT-PCR and Western immunoblot analysis. Aminoguanidine, a selective iNOS inhibitor, attenuated LPS-induced hepatic injury and hypotension, but did not prevent gut I/R-induced hepatic injury. In contrast, the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester aggravated liver damage from both LPS and gut I/R. These data indicate that iNOS plays a role in mediating LPS-induced hepatic injury, but not gut I/R-induced hepatic injury. The data also suggest that the constitutive isoforms of NOS play a hepatoprotective role in both models of hepatic injury.
authors.forename: Terrence H
authors.initials: TH
authors.lastname: Liu
authors.forename: Emily K
authors.initials: EK
authors.lastname: Robinson
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Helmer
authors.forename: Sonlee D
authors.initials: SD
authors.lastname: West
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Castaneda
authors.forename: Lily
authors.initials: L
authors.lastname: Chang
authors.forename: David W
authors.initials: DW
authors.lastname: Mercer
mesh_terms: D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015153:Blotting, Western; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology* / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000777:Anesthetics; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D019331:NG-Nitroarginine Methyl Ester