PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.


Autoria(s): Moral, Raimundo M G del; Gómez-Morales, Mercedes; Hernández-Cortés, Pedro; Aguilar, David; Caballero, Trinidad; Aneiros-Fernández, Jose; Caba-Molina, Mercedes; Rodríguez-Martínez, M Dolores; Peralta, Andreina; Galindo-Moreno, Pablo; Osuna, Antonio; Oliver, F Javier; Moral, Raimundo G del; O'Valle, Francisco
Data(s)

28/01/2015

28/01/2015

2013

Resumo

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.

Journal Article; Research Support, Non-U.S. Gov't;

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”

Identificador

Moral 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; 2013:486574

1537-744X (Online)

PMC3844238

http://hdl.handle.net/10668/1810

24319370

10.1155/2013/486574

Idioma(s)

en

Publicador

Hindawi Publishing Corporation

Relação

The Scientific World Journal

http://www.hindawi.com/journals/tswj/2013/486574/

Direitos

Acceso abierto

Palavras-Chave #poly(ADP-ribose)polymerase-1, mouse #3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone #Frio #Isquemia fría #Riñón #Necrosis tubular aguda #Ratones #Ratones consanguíneos C57BL #Ratones noqueados #Microscopía electrónica #Piperidinas #Poli(ADP-Ribosa) polimerasas #Daño por reperfusión #Animales #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, Western #Medical Subject Headings::Phenomena and Processes::Physical Phenomena::Thermodynamics::Temperature::Cold Temperature #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Preservation, Biological::Tissue Preservation::Cold Ischemia #Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Isoquinolines #Medical Subject Headings::Anatomy::Urogenital System::Urinary Tract::Kidney #Medical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury::Kidney Tubular Necrosis, Acute #Medical Subject Headings::Check Tags::Male #Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice #Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred C57BL #Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockout #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Microscopy::Microscopy, Electron #Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Piperidines #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Pentosyltransferases::ADP Ribose Transferases::Poly(ADP-ribose) Polymerases #Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications::Reperfusion Injury #Medical Subject Headings::Organisms::Eukaryota::Animals
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/published

Artículo