Intrahepatic accumulation of nitrotyrosine in chronic viral hepatitis is associated with histological severity of liver disease.
OBJECTIVE
The toxicity of nitric oxide is thought to be engendered, at least in part, by its reaction with superoxide yielding peroxynitrite, a potent oxidant that promotes the formation of nitrotyrosine within cells and tissue lesions. In this study we assessed the intrahepatic localization and distribution of the inducible nitric oxide synthase (iNOS) and nitrotyrosine (NTY) in patients with viral and non-viral liver disease.


METHODS
We carried out single and double immunostaining experiments on cryostat liver biopsy sections using monoclonal antibodies against iNOS and NTY. We also performed a comparative analysis between the intrahepatic immunostaining score of NTY and the histological activity index of chronic viral hepatitis.


RESULTS
We found a marked hepatocellular expression of iNOS with a diffuse lobular pattern in all liver samples from patients with viral liver disease, whereas NTY localization was mainly restricted to cellular foci consisting of hepatocytes and Kupffer cells. Interestingly, we demonstrated by means of double immunostaining experiments the existence of hepatocellular co-localization of iNOS and NTY in the majority of NTY-expressing liver cells. The amount of NTY was significantly higher in liver biopsies from viral liver disease than in non-viral liver disease. In addition, a statistically significant association between the intrahepatic amount of NTY and the severity of viral liver disease was found.


CONCLUSIONS
Nitric oxide-mediated nitration of hepatocellular proteins is markedly induced in the inflamed liver tissue from patients with chronic viral hepatitis, and appears to be associated with the histological severity of viral chronic liver disease.
García-Monzón
C
C
Hepatology Unit, Hospital Universitario Santa Cristina, Madrid, Spain. garciamonzon@teleline.es
Majano
P L
PL
Zubia
I
I
Sanz
P
P
Apolinario
A
A
Moreno-Otero
R
R
D000328:Adult; D005260:Female; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000473:pathology*; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007158:Immunologic Techniques; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012720:Severity of Illness Index; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II