title: Evidence for a protective role of trimetazidine during cold ischemia: targeting inflammation and nephron mass.
abstract: 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.
authors: Unité de Transplantation Expérimentale, Département de Génétique Animale, Institut National de Recherche Agronomique, Domaine du Magneraud, BP 52, Surgères 17700, France.
authors: Jean-Pierre
authors: JP
authors: Faure
authors: Herve
authors: H
authors: Baumert
authors: Zeqiu
authors: Z
authors: Han
authors: Jean Michel
authors: JM
authors: Goujon
authors: Frederic
authors: F
authors: Favreau
authors: Delphine
authors: D
authors: Dutheil
authors: Isabelle
authors: I
authors: Petit
authors: Michel
authors: M
authors: Barriere
authors: Claude
authors: C
authors: Tallineau
authors: Jean Paul
authors: JP
authors: Tillement
authors: Michel
authors: M
authors: Carretier
authors: Gerard
authors: G
authors: Mauco
authors: Vassilios
authors: V
authors: Papadopoulos
authors: Thierry
authors: T
authors: Hauet
mesh_terms: 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*
chemical_list: D014292:Trimetazidine