Role of anti-tumor necrosis factor-?? in ischemia/reperfusion injury in isolated rat liver in a blood-free environment

Autor: Orit Papo, Ella Kaganovsky, Bernardo A. Vidne, Tatyana Krasnov, Ziv Ben-Ari, Idan Burstein, Edith Hochhauser, Alexey Vamichkim
Rok vydání: 2002
Předmět:
Zdroj: Transplantation. 73:1875-1880
ISSN: 0041-1337
Popis: BACKGROUND Warm ischemia/reperfusion injury during liver transplantation is the most important cause of primary nonfunction of liver allografts. Tumor-necrosis factor (TNF)-alpha apparently mediates tissue damage by inducing apoptosis and/or necrosis in liver transplants. The aim of the study was to determine, using an isolated rat liver model, if pretreatment with anti-TNF-alpha monoclonal antibodies can attenuate ischemia/reperfusion liver injury. Specifically, its effect on liver cell apoptosis through the modulation of caspase activity was examined in a blood-free environment. METHODS Isolated rat livers were perfused with Krebs-Henseleit solution and randomly divided into three groups: (1) continuous perfusion for 165 min (control); (2) perfusion for 90 min, break for 60 min (ischemia), and reperfusion for 15 min; (3) as with group 2, but with administration of monoclonal mouse anti-rat TNF-alpha monoclonal antibodies before induction of ischemia. Caspase-3- and -9-like activity was measured by fluorometric assay, and apoptotic cells were identified by morphological criteria and application of the terminal deoxnucleotidyl transferase-mediated dUTP nick-end-labeling (Tunel) assay. RESULTS Portal pressure increased significantly in group 2 (14.8+/-2.3 mm Hg) compared to group 3, which showed no change (P
Databáze: OpenAIRE