title: Preconditioning with a novel metallopharmaceutical NO donor in anesthetized rats subjected to brain ischemia/reperfusion.
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.
authors.affiliation: Department of Surgery, Federal University of Ceará, R. Professor Costa Mendes, 1608/3º Andar, Fortaleza, CE, CEP:60430-140, Brazil. marciowilker@bol.com.br
authors.forename: Marcio Wilker Soares
authors.initials: MW
authors.lastname: Campelo
authors.forename: Reinaldo Barreto
authors.initials: RB
authors.lastname: Oriá
authors.forename: Luiz Gonzaga de França
authors.initials: LG
authors.lastname: Lopes
authors.forename: Gerly Anne de Castro
authors.initials: GA
authors.lastname: Brito
authors.forename: Armenio Aguiar dos
authors.initials: AA
authors.lastname: Santos
authors.forename: Raquel Cavalcante de
authors.initials: RC
authors.lastname: Vasconcelos
authors.forename: Francisco Ordelei Nascimento da
authors.initials: FO
authors.lastname: Silva
authors.forename: Beatrice Nuto
authors.initials: BN
authors.lastname: Nobrega
authors.forename: Moisés Tolentino
authors.initials: MT
authors.lastname: Bento-Silva
authors.forename: Paulo Roberto Leitão de
authors.initials: PR
authors.lastname: Vasconcelos
mesh_terms: D000758:Anesthesia / Q000379:methods; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D017975:Ruthenium Compounds / Q000008:administration & dosage*
chemical_list: D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D026361:Reactive Nitrogen Species; D017975:Ruthenium Compounds