Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and ta...

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Autores principales: Cicora, Federico, Roberti, Javier, Vasquez, Daniela N., Guerrieri, Diego, Lausada, Natalia Raquel, Cicora, P., Palti, G., Chuluyan, E., González, Pedro Horacio, Stringa, Pablo Luis, Raimondi, Jorge Clemente
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Ciencias Médicas
Acute tubular necrosis
Apoptosis
Donor preconditioning
Rapamycin
Tacrolimus
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/127124
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-127124
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Acute tubular necrosis
Apoptosis
Donor preconditioning
Rapamycin
Tacrolimus
spellingShingle Ciencias Médicas
Acute tubular necrosis
Apoptosis
Donor preconditioning
Rapamycin
Tacrolimus
Cicora, Federico
Roberti, Javier
Vasquez, Daniela N.
Guerrieri, Diego
Lausada, Natalia Raquel
Cicora, P.
Palti, G.
Chuluyan, E.
González, Pedro Horacio
Stringa, Pablo Luis
Raimondi, Jorge Clemente
Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
topic_facet Ciencias Médicas
Acute tubular necrosis
Apoptosis
Donor preconditioning
Rapamycin
Tacrolimus
description Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia–reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.
format Articulo
Articulo
author Cicora, Federico
Roberti, Javier
Vasquez, Daniela N.
Guerrieri, Diego
Lausada, Natalia Raquel
Cicora, P.
Palti, G.
Chuluyan, E.
González, Pedro Horacio
Stringa, Pablo Luis
Raimondi, Jorge Clemente
author_facet Cicora, Federico
Roberti, Javier
Vasquez, Daniela N.
Guerrieri, Diego
Lausada, Natalia Raquel
Cicora, P.
Palti, G.
Chuluyan, E.
González, Pedro Horacio
Stringa, Pablo Luis
Raimondi, Jorge Clemente
author_sort Cicora, Federico
title Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
title_short Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
title_full Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
title_fullStr Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
title_full_unstemmed Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
title_sort preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/127124
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