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Neurochemical Research

, Volume 37, Issue 4, pp 749–758 | Cite as

Preconditioning with a Novel Metallopharmaceutical NO Donor in Anesthetized Rats Subjected to Brain Ischemia/Reperfusion

  • Marcio Wilker Soares Campelo
  • Reinaldo Barreto Oriá
  • Luiz Gonzaga de França Lopes
  • Gerly Anne de Castro Brito
  • Armenio Aguiar dos Santos
  • Raquel Cavalcante de Vasconcelos
  • Francisco Ordelei Nascimento da Silva
  • Beatrice Nuto Nobrega
  • Moisés Tolentino Bento-Silva
  • Paulo Roberto Leitão de Vasconcelos
Original Paper

Abstract

Rut-bpy is a novel nitrosyl–ruthenium complex releasing NO into the vascular system. We evaluated the effect of Rut-bpy (100 mg/kg) on a rat model of brain stroke. Forty rats were assigned to four groups (Saline solution [SS], Rut-bpy, SS+ischemia–reperfusion [SS+I/R] and Rut-bpy+ischemia–reperfusion [Rut-bpy+I/R]) with their mean arterial pressure (MAP) continuously monitored. The groups were submitted (SS+I/R and Rut-bpy+I/R) or not (SS and Rut-bpy) to incomplete global brain ischemia by occlusion of the common bilateral carotid arteries during 30 min followed by reperfusion for further 60 min. Thirty minutes before ischemia, rats were treated pairwise by intraperitoneal injection of saline solution or Rut-bpy. At the end of experiments, brain was removed for triphenyltetrazolium chloride staining in order to quantify the total ischemic area. In a subset of rats, hippocampus was obtained for histopathology scoring, nitrate and nitrite measurements, immunostaining and western blotting of the nuclear factor- κB (NF-κB). Rut-bpy pre-treatment decreased MAP variations during the transition from brain ischemia to reperfusion and decreased the fractional injury area. Rut-bpy pre-treatment reduced NF-κB hippocampal immunostaining and protein expression with improved histopathology scoring as compared to the untreated operated control. In conclusion, Rut-bpy improved the total brain infarction area and hippocampal neuronal viability in part by inhibiting NF-κB signaling and helped to stabilize the blood pressure during the transition from ischemia to reperfusion.

Keywords

Brain Ischemia–reperfusion Nitric oxide Nitrosyl–ruthenium complex Nuclear factor-κB 

Notes

Acknowledgments

We are in debt to PhD. Prof. Renata F. C. Leitão, Rossângela Barreto, Antônio Haroldo Pinheiro Ferreira, and Maria Silvandira França Pinheiro for their helpful technical assistance. CNPq and FUNCAP scholarships and research grants supported this work.

Conflict of interest

There are no actual or potential conflicts of interests.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Marcio Wilker Soares Campelo
    • 1
  • Reinaldo Barreto Oriá
    • 2
  • Luiz Gonzaga de França Lopes
    • 3
  • Gerly Anne de Castro Brito
    • 2
  • Armenio Aguiar dos Santos
    • 4
  • Raquel Cavalcante de Vasconcelos
    • 5
  • Francisco Ordelei Nascimento da Silva
    • 3
  • Beatrice Nuto Nobrega
    • 5
  • Moisés Tolentino Bento-Silva
    • 2
  • Paulo Roberto Leitão de Vasconcelos
    • 1
  1. 1.Department of SurgeryFederal University of CearáFortalezaBrazil
  2. 2.Department of MorphologyFederal University of CearáFortalezaBrazil
  3. 3.Department of Organic and Inorganic ChemistryFederal University of CearáFortalezaBrazil
  4. 4.Department of Physiology and PharmacologyFederal University of CearáFortalezaBrazil
  5. 5.Student of the Medical SchoolFederal University of CearáFortalezaBrazil

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