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: Raimundo M G del Moral, Mercedes Gómez-Morales, Pedro Hernández-Cortés, David Aguilar, Trinidad Caballero, Jose Aneiros-Fernández, Mercedes Caba-Molina, M Dolores Rodríguez-Martínez, Andreina Peralta, Pablo Galindo-Moreno, Antonio Osuna, F Javier Oliver, Raimundo G del Moral, Francisco O'Valle
• Journal: TheScientificWorldJournal (ScientificWorldJournal) Vol. 2013 Pg. 486574 ( 2013) ISSN: 1537-744X [Electronic] United States
• PMID: 24319370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoquinolines
• Piperidines
• Poly(ADP-ribose) Polymerase Inhibitors
• 3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone
• Parp1 protein, mouse
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases

Topics

• Animals
• Blotting, Western
• Cold Temperature
• Ischemia (pathology)
• Isoquinolines (pharmacology)
• Kidney (blood supply, pathology, ultrastructure)
• Kidney Tubular Necrosis, Acute (pathology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Electron
• Piperidines (pharmacology)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (physiology)
• Reperfusion Injury (pathology, prevention & control)