EVIDENCE FOR IN-VIVO PEROXYNITRITE PRODUCTION IN HUMAN CHRONIC HEPATITIS

During inflammation nitric oxide reacts at near diffusion limited rate s with superoxide to form the strong oxidant peroxynitrite. Nitration on the ortho position is a major product of peroxynitrite attack on pr oteins. In the present study we investigated whether immunohistochemic al detection of nitrotyrosine (footprint of peroxynitrite) can be asso ciated with human hepatitis. Paraffin-embedded liver tissue biopsies f rom patients with chronic active hepatitis, chronic active hepatitis p lus cirrhosis and chronic persistent hepatitis exhibit significant spe cific immunostaining with the antibody to nitrotyrosine. Positive stai ning was found in 57% and 72% of tissue specimens from patients with c hronic hepatitis and cirrhosis, respectively. Immunohistochemical stai ning of nitrotyrosine residues was found in the hepatocytes and Kuppff er cells of the necrotic area. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are gen erated in human hepatitis and may be involved in its pathogenesis. (C) 1998 Elsevier Science Inc.