Intrahepatic accumulation of nitrotyrosine in chronic viral hepatitis is associated with histological severity of liver disease

Background/Aims: 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 a nd tissue lesions. In this study we assessed the intrahepatic localization and distribution of the inducible nitric oxide synthase (iNOS) and nitrotyr osine (NTY) in patients with viral and non-viral liver disease, Methods: We carried out single and double immunostaining experiments on cry ostat liver biopsy sections using monoclonal antibodies against iNOS and NT Y, We also performed a comparative analysis between the intrahepatic immuno staining 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 diseas e, whereas NTY localization was mainly restricted to cellular foci consisti ng of hepatocytes and Kupffer cells. Interestingly, we demonstrated by mean s of double immunostaining experiments the existence of hepatocellular co-l ocalization of iNOS and NTY in the majority of NTY-expressing liver cells. The amount of NTY was significantly higher in liver biopsies from viral liv er disease than in non-viral liver disease. In addition, a statistically si gnificant association between the intrahepatic amount of NTY and the severi ty of viral liver disease was found, Conclusions: Nitric oxide-mediated nitration of hepatocellular proteins is markedly induced in the inflamed liver tissue from patients,vith chronic vi ral hepatitis, and appears to be associated with the histological severity of viral chronic liver disease.