The combination of ischemic preconditioning and liver Bcl-2 overexpression is a suitable strategy to prevent liver and lung damage after hepatic ischemia-reperfusion.
The present study evaluates the effectiveness of ischemic preconditioning and Bcl-2 overexpression against the liver and lung damage that follow hepatic ischemia-reperfusion and investigates the underlying protective mechanisms. Preconditioning and Bcl-2, respectively, reduced the increased tumor necrosis factor (TNF) and macrophage inflammatory protein-2 (MIP)-2 levels observed after hepatic reperfusion. Bcl-2 overexpression or anti-MIP-2 pretreatment seems to be more effective than preconditioning or anti-TNF pretreatment against inflammatory response, microcirculatory disorders, and subsequent hepatic ischemia-reperfusion injury. Furthermore, each one of these strategies individually was unable to completely inhibit hepatic injury. The combination of preconditioning and Bcl-2 overexpression as well as the combined anti-TNF and anti-MIP-2 pretreatment totally prevented hepatic injury, whereas the benefits of preconditioning and Bcl-2 were abolished by TNF and MIP-2. In contrast to preconditioning, Bcl-2 did not modify lung damage induced by hepatic reperfusion. This could be explained by the differential effect of both treatments on TNF release. Anti-TNF therapy or preconditioning, by reducing TNF release, reduced pulmonary inflammatory response, whereas the benefits of preconditioning on lung damage were abolished by TNF. Thus, the induction of both Bcl-2 overexpression in liver and preconditioning, as well as pharmacological strategies that simulated their benefits, such as anti-TNF and anti-MIP-2 therapies, could be new strategies aimed to reduce lung damage and inhibit the hepatic injury associated with hepatic ischemia-reperfusion.
Peralta
Carmen
C
Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CSIC-IDIBAPS, Barcelona, Spain.
Perales
José Carlos
JC
Bartrons
Ramón
R
Mitchell
Claudia
C
Gilgenkrantz
Hélène
H
Xaus
Carme
C
Prats
Neus
N
Fernández
Leticia
L
Gelpí
Emilio
E
Panés
Julia
J
Roselló-Catafau
Juan
J
D000818:Animals; D019194:Ischemic Preconditioning; D008099:Liver / Q000473:pathology*; D008102:Liver Circulation; D008168:Lung / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D011652:Pulmonary Circulation; D015427:Reperfusion Injury / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2