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

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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.

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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.

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Authors and Affiliations

  1. Department of Surgery, Federal University of Ceará, R. Professor Costa Mendes, 1608/3º Andar, Fortaleza, CE, CEP:60430-140, Brazil

    Marcio Wilker Soares Campelo & Paulo Roberto Leitão de Vasconcelos

  2. Department of Morphology, Federal University of Ceará, Fortaleza, Brazil

    Reinaldo Barreto Oriá, Gerly Anne de Castro Brito & Moisés Tolentino Bento-Silva

  3. Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, Brazil

    Luiz Gonzaga de França Lopes & Francisco Ordelei Nascimento da Silva

  4. Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil

    Armenio Aguiar dos Santos

  5. Student of the Medical School, Federal University of Ceará, Fortaleza, Brazil

    Raquel Cavalcante de Vasconcelos & Beatrice Nuto Nobrega

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  1. Marcio Wilker Soares Campelo
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  2. Reinaldo Barreto Oriá
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Correspondence to Marcio Wilker Soares Campelo.

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Campelo, M.W.S., Oriá, R.B., de França Lopes, L.G. et al. Preconditioning with a Novel Metallopharmaceutical NO Donor in Anesthetized Rats Subjected to Brain Ischemia/Reperfusion. Neurochem Res 37, 749–758 (2012). https://doi.org/10.1007/s11064-011-0669-x

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  • DOI: https://doi.org/10.1007/s11064-011-0669-x

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