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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/32049

Title: PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia
Authors: Moral, Raimundo M.G. del
Gómez-Morales, Mercedes
Hernández-Cortés, Pedro
Aguilar, David
Caballero, Trinidad
Aneiros-Fernández, José
Caba-Molina, Mercedes
Rodríguez-Martínez, María Dolores
Peralta, Andreina
Galindo-Moreno, Pablo
Osuna Ortega, Antonio
Oliver Pozo, Francisco Javier
García del Moral, Raimundo
O'Valle, Francisco
Issue Date: 2013
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 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.
Sponsorship: Funding: This research was supported by CTS no. 138 Research Group and from the Carlos III Health Institute of the Spanish Ministery of Health and Consumer Affairs (Red de Investigación Renal, REDinREN 012/0021/0025). “FEDER una manera de hacer Europa”.
Publisher: Hindawi Publishing Corporation
Keywords: Adp-ribose
Synthetase
Human poly(adp-ribose)
Polymerase-1
Reperfusion injury
DNA damage
Dysfunction
Domain
Disruption
Expression
Stress
URI: http://hdl.handle.net/10481/32049
ISSN: 1537-744X
Citation: Moral, R.M.G.; et al. PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. Scientific World Journal, 2013: 486574 (2013). [http://hdl.handle.net/10481/32049]
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