title: PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.
abstract: 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.
authors: Provincial UGC Intercentre, Department of ICU, Granada, Spain.
authors: Raimundo M G
authors: RM
authors: del Moral
authors: Mercedes
authors: M
authors: Gómez-Morales
authors: Pedro
authors: P
authors: Hernández-Cortés
authors: David
authors: D
authors: Aguilar
authors: Trinidad
authors: T
authors: Caballero
authors: Jose
authors: J
authors: Aneiros-Fernández
authors: Mercedes
authors: M
authors: Caba-Molina
authors: M Dolores
authors: MD
authors: Rodríguez-Martínez
authors: Andreina
authors: A
authors: Peralta
authors: Pablo
authors: P
authors: Galindo-Moreno
authors: Antonio
authors: A
authors: Osuna
authors: F Javier
authors: FJ
authors: Oliver
authors: Raimundo G
authors: RG
authors: del Moral
authors: Francisco
authors: F
authors: O'Valle
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003080:Cold Temperature; D007511:Ischemia / Q000473:pathology*; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010880:Piperidines / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
chemical_list: D007546:Isoquinolines; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C108729:3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases