Nitrotyrosine formation and heme oxygenase-1 expression in endotoxemic cirrhotic rats.
BACKGROUND
Endotoxemia increases hepatic toxicity and mortality in cirrhosis. Because the mechanism of augmented hepatotoxicity in endotoxemic cirrhotic rats is still unclear, we wanted to investigate whether oxidative and nitrosative stress play a causative role in lipopolysaccharide (LPS)-treated cirrhotic rats.


METHODS
Liver cirrhosis was produced by the administration of thioacetamide (0.3 g/L of tap water) for a period of 3 months in rats. At the end of this period, cirrhotic rats were sacrificed 6 h after LPS injection (5 mg/kg, intraperitoneally). Serum transaminase activities, plasma total nitrite and nitrotyrosine (NT) levels as well as hepatic lipid peroxides, NT formation and heme oxygenase 1 (HO-1) expression were determined.


RESULTS
LPS administration to cirrhotic rats caused further increases in serum transaminase activities, and plasma total nitrite and NT levels as well as hepatic lipid peroxide levels as compared to cirrhotic rats. Hepatic NT formation and HO-1 expression were also found to be increased in LPS-injected cirrhotic rats.


CONCLUSIONS
Our results indicate that increased oxidative and nitrosative stress may have a synergistic effect in LPS-augmented hepatotoxicity in cirrhotic rats.
Doğru-Abbasoğlu
Semra
S
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey. sdabbasoglu@yahoo.com
Parildar-Karpuzoğlu
Hande
H
Balkan
Jale
J
Aykaç-Toker
Gülçin
G
Uysal
Müjdat
M
D000818:Animals; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000096:biosynthesis*; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis
D008070:Lipopolysaccharides; D009573:Nitrites; D013853:Thioacetamide; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D051547:Heme Oxygenase-1