Evidence for in vivo peroxynitrite production in human chronic hepatitis

被引:40
作者
Cuzzocrea, S
Zingarelli, B
Villari, D
Caputi, AP
Longo, G
机构
[1] Univ Messina, Sch Med, Inst Pharmacol, I-98123 Messina, Italy
[2] Univ Messina, Sch Med, Dept Pathol, I-98123 Messina, Italy
[3] Univ Messina, Sch Med, Dept Internal Med, I-98123 Messina, Italy
[4] Childrens Hosp, Med Ctr, Div Crit Care, Cincinnati, OH 45229 USA
关键词
hepatitis; cirrhosis; nitrotyrosine; immunohistochemistry;
D O I
10.1016/S0024-3205(98)00252-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
During inflammation nitric oxide reacts at near diffusion limited rates with superoxide to form the strong oxidant peroxynitrite. Nitration on the ortho position is a major product of peroxynitrite attack on proteins. In the present study we investigated whether immunohistochemical detection of nitrotyrosine (footprint of peroxynitrite) can be associated with human hepatitis. Paraffin-embedded liver tissue biopsies from patients with chronic active hepatitis, chronic active hepatitis plus cirrhosis and chronic persistent hepatitis exhibit significant specific immunostaining with the antibody to nitrotyrosine. Positive staining was found in 57% and 72% of tissue specimens from patients with chronic hepatitis and cirrhosis, respectively. Immunohistochemical staining of nitrotyrosine residues was found in the hepatocytes and Kuppffer cells of the necrotic area. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are generated in human hepatitis and may be involved in its pathogenesis. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:PL25 / PL30
页数:6
相关论文
共 30 条
[1]   CONSTITUTIVE AND INDUCIBLE NITRIC-OXIDE SYNTHASE GENE-EXPRESSION, REGULATION, AND ACTIVITY IN HUMAN LUNG EPITHELIAL-CELLS [J].
ASANO, K ;
CHEE, CBE ;
GASTON, B ;
LILLY, CM ;
GERARD, C ;
DRAZEN, JM ;
STAMLER, JS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (21) :10089-10093
[2]   APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE [J].
BECKMAN, JS ;
BECKMAN, TW ;
CHEN, J ;
MARSHALL, PA ;
FREEMAN, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) :1620-1624
[3]   KINETICS OF SUPEROXIDE DISMUTASE-CATALYZED AND IRON-CATALYZED NITRATION OF PHENOLICS BY PEROXYNITRITE [J].
BECKMAN, JS ;
ISCHIROPOULOS, H ;
ZHU, L ;
VANDERWOERD, M ;
SMITH, C ;
CHEN, J ;
HARRISON, J ;
MARTIN, JC ;
TSAI, M .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 298 (02) :438-445
[4]   EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY [J].
BECKMANN, JS ;
YE, YZ ;
ANDERSON, PG ;
CHEN, J ;
ACCAVITTI, MA ;
TARPEY, MM ;
WHITE, CR ;
BECKMAN, JS .
BIOLOGICAL CHEMISTRY HOPPE-SEYLER, 1994, 375 (02) :81-88
[5]   INDUCTION OF NITRIC-OXIDE SYNTHASE BY CYTOKINES IN VASCULAR SMOOTH-MUSCLE CELLS [J].
BUSSE, R ;
MULSCH, A .
FEBS LETTERS, 1990, 275 (1-2) :87-90
[6]  
Buttery LDK, 1996, LAB INVEST, V75, P77
[7]  
COLUMBANO A, 1981, CANCER RES, V41, P2079
[8]  
Crow J P, 1995, Curr Top Microbiol Immunol, V196, P57
[9]  
Crow J P, 1995, Adv Pharmacol, V34, P17
[10]   Beneficial effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase in a rat model of splanchnic artery occlusion and reperfusion [J].
Cuzzocrea, S ;
Zingarelli, B ;
Costantino, G ;
Szabo, A ;
Salzman, AL ;
Caputi, AP ;
Szabo, C .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 121 (06) :1065-1074