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.

A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in mice

“…There is a growing body of evidence that synthetic NO donors have efficacy in animal models of cerebral ischemia. For example, intraperitoneal injection of NO donor Rut-bpy prior to ischemia/reperfusion reduced brain infarct zone and improved viability of hippocampal neurons [7]. Another NO donor, NOC-18, protected brain mitochondria against ischemia-induced dysfunction [2].…”

New metallophamaceutic reduced renal injury induced by non-steroidal anti-inflammatory

“…NFKB activated in podocytes. NFkB activation and NO production by NOSi are known to lead to cell damage, as shown in experimental rat model 8 , and also promote glomerulonephritis 22 .…”

“…Currently, a metallopharmaceutical named Rut-bpy (Cis-[Ru(bpy) 2 (SO3)(NO)]PF 6 ) can release NO in vitro and in vivo, as well as it can reduce inflammatory processes through NF-kB inhibition 7,8 .…”

Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy

“…This may suggest a beneficial role of nNOS during early stages of epileptogenesis in contrast to its proconvulsive role during acute seizures onset (SE). It has been shown that a transient increase in nNOS, following insult to the brain, protect neurons by S-nitrosylation of NR2B subunit of NMDAR to control excessive calcium influx (Gidday et al, 1999; Gonzale-Zulueta et al, 2000; Campelo et al, 2012). Since we did not observe expected modifications in early epileptogenesis by inhibiting nNOS with L-NPA, we focused our investigation on the role of iNOS in epileptogenesis.…”

“…This may suggest a beneficial role of nNOS during the early stages of epileptogenesis in contrast to its proconvulsive role during acute seizure onset (i.e., SE). It has been shown that a transient increase in nNOS, following insult to the brain, protects neurons by S-nitrosylation of the NR2B subunit of NMDAR to control excessive calcium influx (Campelo et al, 2012;Gidday et al, 1999;Gonzalez-Zulueta et al, 2000).…”