Evidence for a protective role of trimetazidine during cold ischemia: targeting inflammation and nephron mass.
Ischemia-reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in HEH after 24 hr and particularly 48- and 72-hr cold storage than in CEL and UW. TMZ improved the preservation quality when added to the different solutions tested, particularly after 48- and 72-hr cold storage. Interstitial fibrosis and tubular atrophy were reduced in HEH with TMZ. CD4(+) T-cell infiltration was also modulated by the preservation conditions. Peripheral-type benzodiazepine receptor (PBR) positive cells infiltration was also modulated by preservation conditions. TMZ was efficient to reduce IRI when added in the various preservation solutions. These results suggest that protection of the mitochondrial function should be a major target to limit IRI. In addition, this study outlines the role of CD4(+) T cells and PBR expression in inflammatory responses after IRI.
Faure
Jean-Pierre
JP
Unité de Transplantation Expérimentale, Département de Génétique Animale, Institut National de Recherche Agronomique, Domaine du Magneraud, BP 52, Surgères 17700, France.
Baumert
Herve
H
Han
Zeqiu
Z
Goujon
Jean Michel
JM
Favreau
Frederic
F
Dutheil
Delphine
D
Petit
Isabelle
I
Barriere
Michel
M
Tallineau
Claude
C
Tillement
Jean Paul
JP
Carretier
Michel
M
Mauco
Gerard
G
Papadopoulos
Vassilios
V
Hauet
Thierry
T
D000818:Animals; D003080:Cold Temperature; D016503:Drug Delivery Systems / Q000379:methods*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D009393:Nephritis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009399:Nephrons / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D013552:Swine; D014182:Transplantation, Autologous; D014292:Trimetazidine / Q000627:therapeutic use*
D014292:Trimetazidine