e-Article
Regulation of postischemic liver injury following different durations of ischemia
Document Type
Abstract
Author
Source
The American Journal of Physiology. March, 2003, Vol. 284 Issue 3, pG536, 10 p.
Subject
Language
ISSN
0002-9513
Abstract
The objective of this study was to define the relationship among Kupffer cells, [O.sup.-.sub.2] production, and TNF-[alpha] expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-[alpha], and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-[alpha] expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-[alpha] but were dependent on Kupffer cells and NADPH oxidase-independent production of [O.sup.-.sub.2]. However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived [O.sup.-.sub.2], and TNF-[alpha] expression. We conclude that the sources for [O.sup.-.sub.2] formation and the relative importance of TNF-[alpha] in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia. transplantation; leukocytes; reactive oxygen species; proinfiammatory cytokines; NADPH oxidase