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Effects of pentoxifylline pretreatment on Kupffer cells in rat liver transplantation
Author(s) -
Kozaki Koichi,
Egawa Hiroto,
Bermudez Luiz,
Keefe Emmet B.,
So Samuel K.,
Esquivel Carlos O.
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210429
Subject(s) - pentoxifylline , viaspan , transplantation , kupffer cell , medicine , liver transplantation , tumor necrosis factor alpha , hepatology , phosphodiesterase inhibitor , lipopolysaccharide , in vivo , pharmacology , necrosis , liver injury , cytokine , stimulation , endocrinology , immunology , biology , microbiology and biotechnology
Abstract Previous research with pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor, suggests that this drug may be capable of suppressing the activation of Kupffer cells and thereby help decrease liver injury after transplantation. To investigate this possibility, the current study sought to determine whether the release of O 2 − and tumor necrosis factor (TNF) from Kupffer cells in donor livers can be suppressed if the organs are exposed to PTX before preservation. In an in vitro experiment, rat livers were flushed with PTX (25 mg/kg body weight) in University of Washington (UW) solution or UW solution alone (control) and then and stored in UW solution for either 4 or 24 hours. Kupffer cells then were purified and their degree of activation determined by measuring O 2 − release and the production of TNF after lipopolysaccharide stimulation. In an in vivo experiment, a group of rats underwent orthotopic liver transplantation with grafts prepared in the same manner as in the in vitro study. TNF and aspartate transaminase (AST) were measured in blood samples taken 3 hours and 24 hours after transplantation. Compared with controls, the Kupffer cells from grafts pretreated with PTX produced significantly less O 2 − and TNF, and the recipients of PTX‐pretreated grafts had lower levels of TNF and AST 3 hours after transplantation. The current data indicate that O 2 − and TNF production in liver grafts is suppressed by PTX pretreatment. Through its suppressive effect on Kupffer cells, PTX may help minimize preservation‐reperfusion injury and improve graft survival. (H EPATOLOGY 1995; 21:1079–1082.)