PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

• Published in: TheScientificWorld Vol. 2013; no. 2013; pp. 1 - 8
• Main Authors: Peralta, Andreina, Osuna, Antonio, Oliver, F. Javier, del Moral, Raimundo G., O'Valle, Francisco, Rodríguez-Martínez, Mª Dolores, Caba-Molina, Mercedes, Aneiros-Fernández, Jose, Caballero, Trinidad, Aguilar, David, Hernández-Cortés, Pedro, Gómez-Morales, Mercedes, del Moral, Raimundo M. G., Galindo-Moreno, Pablo
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2013; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Apoptosis; Blotting, Western; Body weight; Bone surgery; Cold storage; Cold Temperature; Colleges & universities; Dentistry; DNA repair; Health aspects; Histology, Pathological; Hospitals; Inhibitors; Ischemia; Ischemia - pathology; Isoquinolines - pharmacology; Kidney - blood supply; Kidney - pathology; Kidney - ultrastructure; Kidney Tubular Necrosis, Acute - pathology; Kidney Tubular Necrosis, Acute - prevention & control; Kidneys; Lesions; Male; Medical research; Medicine, Experimental; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Necrosis; Organs; Physiological aspects; Piperidines - pharmacology; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases - physiology; Preconditioning; Proteins; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Rodents; Subgroups; Transcription factors; Transplantation
• ISSN: 2356-6140; 1537-744X; 1537-744X
• DOI: 10.1155/2013/486574

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 Parp10/0 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. Parp10/0 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.