%0 Journal Article
%A Moral, Raimundo M G del
%A Gómez-Morales, Mercedes
%A Hernández-Cortés, Pedro
%A Aguilar, David
%A Caballero, Trinidad
%A Aneiros-Fernández, Jose
%A Caba-Molina, Mercedes
%A Rodríguez-Martínez, M Dolores
%A Peralta, Andreina
%A Galindo-Moreno, Pablo
%A Osuna, Antonio
%A Oliver, F Javier
%A Moral, Raimundo G del
%A O'Valle, Francisco
%T PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.
%D 2013
%U http://hdl.handle.net/10668/1810
%X We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.
%K poly(ADP-ribose)polymerase-1, mouse
%K 3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone
%K Frio
%K Isquemia fría
%K Riñón
%K Necrosis tubular aguda
%K Ratones
%K Ratones consanguíneos C57BL
%K Ratones noqueados
%K Microscopía electrónica
%K Piperidinas
%K Poli(ADP-Ribosa) polimerasas
%K Daño por reperfusión
%K Animales
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