ZJM-289, a Novel Nitric Oxide Donor, Alleviates the Cerebral Ischemic-Reperfusion Injury in Rats

Zhuang, Ping; Jiang, Hui; Zhang, Yihua; Min, Zhen-Li; Ni, Qing-Gui; You, Ran

doi:10.1111/j.1440-1681.2009.05353.x

Cited by 4 publications

(4 citation statements)

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“…The exact role that NO plays after neural injury is a topic that remains under investigation. Some studies have shown that NO could be protective and even necessary to ameliorate tissue damage after injury (Zhuang et al,2009); however, others have provided evidence on the pathogenic effects of this compound (Dawson and Dawson,1998; Liu et al,2000). It seems that the dual role of NO depends on its concentration at the site of injury.…”

Section: Discussionmentioning

confidence: 99%

Immunization with A91 peptide or copolymer‐1 reduces the production of nitric oxide and inducible nitric oxide synthase gene expression after spinal cord injury

García

Silva-García

Mestre

et al. 2011

J of Neuroscience Research

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Immunization with neurally derived peptides (INDP) boosts the action of an autoreactive immune response that has been shown to induce neuroprotection in several neurodegenerative diseases, especially after spinal cord (SC) injury. This strategy provides an environment that promotes neuronal survival and tissue preservation. The mechanisms by which this autoreactive response exerts its protective effects is not totally understood at the moment. A recent study showed that INDP reduces lipid peroxidation. Lipid peroxidation is a neurodegenerative phenomenon caused by the increased production of reactive nitrogen species such as nitric oxide (NO). It is possible that INDP could be interfering with NO production. To test this hypothesis, we examined the effect of INDP on the amount of NO produced by glial cells when cocultured with autoreactive T cells. We also evaluated the amount of NO and the expression of the inducible form of nitric oxide synthase (iNOS) at the injury site of SC-injured animals. The neural-derived peptides A91 and Cop-1 were used to immunize mice and rats with SC injury. In vitro studies showed that INDP significantly reduces the production of NO by glial cells. This observation was substantiated by in vivo experiments demonstrating that INDP decreases the amount of NO and iNOS gene expression at the site of injury. The present study provides substantial evidence on the inhibitory effect of INDP on NO production, helpingour understanding of the mechanisms through which protective autoimmunity promotes neuroprotection.

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Section: Discussionmentioning

confidence: 99%

Immunization with A91 peptide or copolymer‐1 reduces the production of nitric oxide and inducible nitric oxide synthase gene expression after spinal cord injury

García

Silva-García

Mestre

et al. 2011

J of Neuroscience Research

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“…ZJM-289 (0.1-0.2 mmol/kg) under ischaemia/ reperfusion (90 min/24 h) has shown that exogenous supplementation of NO significantly reduces infarct size and water content in rat brain while improving functional recovery. The beneficial effects of ZJM-289 in rat I/R injury models has subsequently been attributed to substantial increases in eNOS, cyclic guanosine monophosphate (cGMP) and NO levels and a concomitant decrease in nNOS activity (Zhuang et al 2010). Similar to these results, treatments of rat models of global cerebral ischaemia with another NO donor, LA-419 (20 mg/kg, 3-6 h before surgery for global ischaemia) have also shown significant decreases in infarct size and cerebral nNOS, iNOS and nitrotyrosine stainings.…”

Section: No Donorsmentioning

confidence: 98%

Current Therapeutic Strategies to Mitigate the eNOS Dysfunction in Ischaemic Stroke

2011

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Impairment of endothelial nitric oxide synthase (eNOS) activity is implicated in the pathogenesis of endothelial dysfunction in many diseases including ischaemic stroke. The modulation of eNOS during and/or following ischaemic injury often represents a futile compensatory mechanism due to a significant decrease in nitric oxide (NO) bioavailability coupled with dramatic increases in the levels of reactive oxygen species that further neutralise NO. However, applications of a number of therapeutic agents alone or in combination have been shown to augment eNOS activity under a variety of pathological conditions by potentiating the expression and/or activity of Akt/eNOS/NO pathway components. The list of these therapeutic agents include NO donors, statins, angiotensin-converting enzyme inhibitors, calcium channel blockers, phosphodiesterase-3 inhibitors, aspirin, dipyridamole and ellagic acid. While most of these compounds exhibit anti-platelet properties and are able to up-regulate eNOS expression in endothelial cells and platelets, others suppress eNOS uncoupling and tetrahydrobiopterin (an eNOS stabiliser) oxidation. As the number of therapeutic molecules that modulate the expression and activity of eNOS increases, further detailed research is required to reveal their mode of action in preventing and/or reversing the endothelial dysfunction.

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“…Nitric oxide (NO) produced by endothelial nitric oxidase (eNOS) reduces apoptosis and confers protection against stroke, whereas pathological concentrations of NO from inducible iNOS and neuronal nitric oxidase (nNOS) lead to apoptosis and are neurotoxic [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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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ZJM-289, a Novel Nitric Oxide Donor, Alleviates the Cerebral Ischemic-Reperfusion Injury in Rats

Cited by 4 publications

References 0 publications

Immunization with A91 peptide or copolymer‐1 reduces the production of nitric oxide and inducible nitric oxide synthase gene expression after spinal cord injury

Immunization with A91 peptide or copolymer‐1 reduces the production of nitric oxide and inducible nitric oxide synthase gene expression after spinal cord injury

Current Therapeutic Strategies to Mitigate the eNOS Dysfunction in Ischaemic Stroke

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

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