TY - JOUR
T1 - Propionyl-L-carnitine prevents early graft dysfunction in allogeneic rat kidney transplantation
AU - Azzollini, Nadia
AU - Cugini, Daniela
AU - Cassis, Paola
AU - Pezzotta, Anna
AU - Gagliardini, Elena
AU - Abbate, Mauro
AU - Arduini, Arduino
AU - Peschechera, Alessandro
AU - Remuzzi, Giuseppe
AU - Noris, Marina
PY - 2008/12
Y1 - 2008/12
N2 - Ischemia-reperfusion injury is an important cause of graft failure. Because carnitine regulates substrate flux and energy balance across membranes which may be deranged in ischemia we determined whether its use was effective in preventing kidney injury in an allogeneic transplant model. Brown Norway rats received a Lewis rat kidney transplant and were then treated with cyclosporine A to avoid rejection. The grafts were stored in Belzer solution supplemented with propionyl-L-carnitine during the cold ischemia period. Compared to rats receiving untreated kidneys but with equal cold ischemia times, the post-transplant serum creatinine values of the carnitine-treated transplants were significantly lower. Histological evaluation 16 h after transplant showed that propionyl-L-carnitine significantly inhibited tubular necrosis and neutrophil infiltration of the allografts and improved the 3 month graft survival. Treated transplants also had decreased lipid peroxidation, inducible nitric oxide synthase expression and protein nitration compared to the untreated grafts. Post-transplant serum creatinine levels were significantly reduced and graft survival was slightly prolonged in rats not receiving cyclosporine A treatment and transplanted with a kidney treated with propionyl-L-carnitine. The efficacy of propionyl-L-carnitine to modulate ischemia-reperfusion injury during transplantation suggests that its use in human transplantation is worth testing.
AB - Ischemia-reperfusion injury is an important cause of graft failure. Because carnitine regulates substrate flux and energy balance across membranes which may be deranged in ischemia we determined whether its use was effective in preventing kidney injury in an allogeneic transplant model. Brown Norway rats received a Lewis rat kidney transplant and were then treated with cyclosporine A to avoid rejection. The grafts were stored in Belzer solution supplemented with propionyl-L-carnitine during the cold ischemia period. Compared to rats receiving untreated kidneys but with equal cold ischemia times, the post-transplant serum creatinine values of the carnitine-treated transplants were significantly lower. Histological evaluation 16 h after transplant showed that propionyl-L-carnitine significantly inhibited tubular necrosis and neutrophil infiltration of the allografts and improved the 3 month graft survival. Treated transplants also had decreased lipid peroxidation, inducible nitric oxide synthase expression and protein nitration compared to the untreated grafts. Post-transplant serum creatinine levels were significantly reduced and graft survival was slightly prolonged in rats not receiving cyclosporine A treatment and transplanted with a kidney treated with propionyl-L-carnitine. The efficacy of propionyl-L-carnitine to modulate ischemia-reperfusion injury during transplantation suggests that its use in human transplantation is worth testing.
KW - Acute allograft rejection
KW - Delayed graft function
KW - Ischemia-reperfusion
KW - Kidney transplantation
KW - Oxidative stress
KW - Propionyl-L-carnitine
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U2 - 10.1038/ki.2008.399
DO - 10.1038/ki.2008.399
M3 - Article
C2 - 19008910
AN - SCOPUS:56549096401
VL - 74
SP - 1420
EP - 1428
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 11
ER -