RT Journal Article T1 PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. A1 Moral, Raimundo M G del A1 Gómez-Morales, Mercedes A1 Hernández-Cortés, Pedro A1 Aguilar, David A1 Caballero, Trinidad A1 Aneiros-Fernández, Jose A1 Caba-Molina, Mercedes A1 Rodríguez-Martínez, M Dolores A1 Peralta, Andreina A1 Galindo-Moreno, Pablo A1 Osuna, Antonio A1 Oliver, F Javier A1 Moral, Raimundo G del A1 O'Valle, Francisco K1 poly(ADP-ribose)polymerase-1, mouse K1 3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone K1 Frio K1 Isquemia fría K1 Riñón K1 Necrosis tubular aguda K1 Ratones K1 Ratones consanguíneos C57BL K1 Ratones noqueados K1 Microscopía electrónica K1 Piperidinas K1 Poli(ADP-Ribosa) polimerasas K1 Daño por reperfusión K1 Animales AB 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. PB Hindawi Publishing Corporation YR 2013 FD 2013 LK http://hdl.handle.net/10668/1810 UL http://hdl.handle.net/10668/1810 LA en NO Moral RMG del, Gómez-Morales M, Hernández-Cortés P, Aguilar D, Caballero T, Aneiros-Fernández J, et al. PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. ScientificWorldJournal; 2013:486574 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 8, 2025