PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia
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...
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Wiley
2013-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2013/486574 |
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| author | Raimundo M. G. del Moral Mercedes Gómez-Morales Pedro Hernández-Cortés David Aguilar Trinidad Caballero Jose Aneiros-Fernández Mercedes Caba-Molina Mª Dolores Rodríguez-Martínez Andreina Peralta Pablo Galindo-Moreno Antonio Osuna F. Javier Oliver Raimundo G. del Moral Francisco O'Valle |
| author_facet | Raimundo M. G. del Moral Mercedes Gómez-Morales Pedro Hernández-Cortés David Aguilar Trinidad Caballero Jose Aneiros-Fernández Mercedes Caba-Molina Mª Dolores Rodríguez-Martínez Andreina Peralta Pablo Galindo-Moreno Antonio Osuna F. Javier Oliver Raimundo G. del Moral Francisco O'Valle |
| author_sort | Raimundo M. G. del Moral |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2b34fbfe3cce491583e2d20af8f53c7b |
| institution | OA Journals |
| issn | 1537-744X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-2b34fbfe3cce491583e2d20af8f53c7b2025-08-20T02:04:10ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/486574486574PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged IschemiaRaimundo M. G. del Moral0Mercedes Gómez-Morales1Pedro Hernández-Cortés2David Aguilar3Trinidad Caballero4Jose Aneiros-Fernández5Mercedes Caba-Molina6Mª Dolores Rodríguez-Martínez7Andreina Peralta8Pablo Galindo-Moreno9Antonio Osuna10F. Javier Oliver11Raimundo G. del Moral12Francisco O'Valle13Provincial UGC Intercentre, Department of ICU, Granada, SpainProvincial UGC Intercentre, Department of ICU, Granada, SpainDepartment of Traumatology and Orthopedic Surgery, IBIMER, “San Cecilio” Clinical Hospital and University of Granada, SpainDepartment of Pathology and IBIMER, School of Medicine, University of Granada, SpainDepartment of Pathology and IBIMER, School of Medicine, University of Granada, SpainProvincial UGC Intercentre, Department of ICU, Granada, SpainProvincial UGC Intercentre, Department of ICU, Granada, SpainDepartment of Pathology and IBIMER, School of Medicine, University of Granada, SpainInstitute of Parasitology and Biomedicine, CSIC, Granada, SpainOral Surgery and Implant Dentistry Department, School of Dentistry, University of Granada, SpainDepartment of Nephrology, “Virgen de las Nieves” Universitary Hospital, Granada, SpainInstitute of Parasitology and Biomedicine, CSIC, Granada, SpainProvincial UGC Intercentre, Department of ICU, Granada, SpainDepartment of Pathology and IBIMER, School of Medicine, University of Granada, SpainWe 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.http://dx.doi.org/10.1155/2013/486574 |
| spellingShingle | Raimundo M. G. del Moral Mercedes Gómez-Morales Pedro Hernández-Cortés David Aguilar Trinidad Caballero Jose Aneiros-Fernández Mercedes Caba-Molina Mª Dolores Rodríguez-Martínez Andreina Peralta Pablo Galindo-Moreno Antonio Osuna F. Javier Oliver Raimundo G. del Moral Francisco O'Valle PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia The Scientific World Journal |
| title | PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia |
| title_full | PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia |
| title_fullStr | PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia |
| title_full_unstemmed | PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia |
| title_short | PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia |
| title_sort | parp inhibition attenuates histopathological lesion in ischemia reperfusion renal mouse model after cold prolonged ischemia |
| url | http://dx.doi.org/10.1155/2013/486574 |
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