Moral, Raimundo M G delGómez-Morales, MercedesHernández-Cortés, PedroAguilar, DavidCaballero, TrinidadAneiros-Fernández, JoseCaba-Molina, MercedesRodríguez-Martínez, M DoloresPeralta, AndreinaGalindo-Moreno, PabloOsuna, AntonioOliver, F JavierMoral, Raimundo G delO'Valle, Francisco2015-01-282015-01-282013Moral RMG del, Gómez-Morales M, Hernández-Cortés P, Aguilar D, Caballero T, Aneiros-Fernández J, et al. PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. ScientificWorldJournal; 2013:486574http://hdl.handle.net/10668/1810Journal Article; Research Support, Non-U.S. Gov't;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.enpoly(ADP-ribose)polymerase-1, mouse3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinoneFrioIsquemia fríaRiñónNecrosis tubular agudaRatonesRatones consanguíneos C57BLRatones noqueadosMicroscopía electrónicaPiperidinasPoli(ADP-Ribosa) polimerasasDaño por reperfusiónAnimalesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, WesternMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Thermodynamics::Temperature::Cold TemperatureMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Preservation, Biological::Tissue Preservation::Cold IschemiaMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::IsoquinolinesMedical Subject Headings::Anatomy::Urogenital System::Urinary Tract::KidneyMedical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury::Kidney Tubular Necrosis, AcuteMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred C57BLMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, KnockoutMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Microscopy::Microscopy, ElectronMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::PiperidinesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Pentosyltransferases::ADP Ribose Transferases::Poly(ADP-ribose) PolymerasesMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications::Reperfusion InjuryMedical Subject Headings::Organisms::Eukaryota::Animalsresearch article24319370open access10.1155/2013/4865741537-744XPMC3844238