title: Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion.
abstract: BACKGROUND
  Ischemia-reperfusion injury after organ transplantation is a major cause of delayed graft function. Prevention of post-transplant ischemia acute renal failure is still elusive.
  
  
  METHODS
  The present study was designed to examine whether propionyl-l-carnitine, an acyl derivative of carnitine involved in fatty acid oxidation pathway and adenosine 5'-triphosphate (ATP) generation of mitochondria, prevented renal function deterioration and structural injury induced by ischemia-reperfusion in an ex vivo rat model of isolated perfused kidney (IPK) preparation and in vivo in a model of syngeneic kidney transplantation.
  
  
  RESULTS
  In the model of ischemia (20 or 40 min)/reperfusion (90 or 70 min) in IPK, untreated kidneys showed a marked reduction of glomerular filtration rate (GFR) and renal perfusate flow (RPF) as compared to baseline, when perfusion was established by restoring effective perfusion pressure to 100 mm Hg. Exposure of kidneys to propionyl-l-carnitine before establishing the ischemia insult to tissue, largely prevented renal function impairment. Pre-exposure of ischemic kidneys to propionyl-l-carnitine largely reduced the percent of lactate dehydrogenase (LDH), a cell injury marker, released into the perfusate after reperfusion as compared to untreated ischemic kidneys. Histologic findings showed very mild post-ischemic lesions in kidneys exposed to propionyl-l-carnitine as compared to untreated ischemic kidneys. Immunohistochemical detection of 4-hydroxynonenal protein adduct, a major product of lipid peroxidation, was very low in kidney infused with propionyl-l-carnitine and exposed to ischemia/reperfusion as compared to untreated ischemic kidneys. ATP levels were not affected by propionyl-l-carnitine treatment. Renal function of kidneys exposed for four hours to cold Belzer UW solution added with propionyl-l-carnitine and transplanted to binephrectomized recipients was largely preserved as compared to untreated ischemic grafts. Propionyl-l-carnitine almost completely prevented polymorphonuclear cell graft infiltration and reduced tubular injury at 16 hours post-transplant.
  
  
  CONCLUSIONS
  These data indicate that propionyl-l-carnitine is of value in preventing decline of renal function that occurs during ischemia-reperfusion. The beneficial effect of propionyl-l-carnitine possibly relates to lowering lipid peroxidation and free radical generation that eventually results in the preservation of tubular cell structure. The efficacy of propionyl-l-carnitine to modulate ischemia-reperfusion injury in these models opens new perspectives for preventing post-transplant delayed graft function.
authors.affiliation: Department of Immunology, Clinics of Organ Transplantation, Mario Negri Institute for Pharmalogical Research, Via Gavazzeni 11, 24125 Bergamo, Rome, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Mister
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Szymczuk
authors.forename: Nadia
authors.initials: N
authors.lastname: Azzollini
authors.forename: Sistiana
authors.initials: S
authors.lastname: Aiello
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Lech
authors.initials: L
authors.lastname: Trochimowicz
authors.forename: Elena
authors.initials: E
authors.lastname: Gagliardini
authors.forename: Arduino
authors.initials: A
authors.lastname: Arduini
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D014185:Transplantation, Isogeneic
chemical_list: C003223:propionylcarnitine; D002331:Carnitine