(−)Deprenyl-N-oxide, a (−)deprenyl metabolite, is cytoprotective after hypoxic injury in PC12 cells, or after transient brain ischemia in gerbils

Szilágyi, G.; Szabó, László; Wappler, Edina A.; Magyar, K.; Nagy, Zoltán

doi:10.1016/j.jns.2009.02.368

Cited by 10 publications

(3 citation statements)

References 23 publications

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“…The effects of the metabolites (e.g. R-amphetamines, R-deprenyl-N-oxide) have also characteristic effects on the basic cell biological mechanisms, which were also demonstrated (Jenei et al 2005;Szende et al 2010;Tekes et al 1988;Szilágyi et al 2009). …”

Section: Discussionmentioning

confidence: 89%

Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes

et al. 2011

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Selegiline (R-deprenyl), a monoamine oxidase-B (MAO-B) inhibitor, has complex pharmacological effect that contributes to treatment of neurodegenerative diseases such as Parkinson's and presumably Alzheimer's disease and might work as an inhibitor of tumor growth. In respect of tumorigenesis and metastasis formation, the controlled modifications of adhesion and migration have high therapeutic significance. In the present study, our purpose was to investigate cell physiological responses (adhesion, chemotaxis and proliferation) induced by selegiline, its metabolites and synthetic derivatives and to find some correlations between the molecular structure and the reported antitumor behavior of the derivatives. Our results demonstrated that both R- and S-deprenyls have the potency to elicit increased adhesion and a chemorepellent activity in monocyte model (Mono Mac 6 cell line derived from monoblastic leukemia); however, only the R-enantiomer proved to be cytotoxic. Among the metabolites R-amphetamine has retained the adhesion inducer and the chemorepellent effect of the parent drug on the most significant level. In contrast, a reversed chemotactic effect and an improved cytotoxic character were detected in the presence of fluoro group (p-fluoro-S-deprenyl). In summary, the adhesion inducer activity, chemorepellent and advantageous cytotoxic effects of selegiline and some derivatives indicate that these drug molecules might have inhibitory effects in metastasis formation in primary tumors.

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Section: Discussionmentioning

confidence: 89%

Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes

et al. 2011

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“…Reduction of MAO-B expression has a neuroprotective effect. MAO-B inhibitors prevent the production of reactive oxygen species and brain injury after ischemia/reperfusion [36, 37]. …”

Section: Discussionmentioning

confidence: 99%

Activation of Alpha-7 Nicotinic Acetylcholine Receptor Reduces Brain Edema in Mice with Ischemic Stroke and Bone Fracture

et al. 2016

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Stroke is an important risk factor for bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) improves, stroke recovery by attenuating inflammation. We hypothesized that activation of α-7 nAchR also improves the blood-brain barrier (BBB) integrity. Permanent distal middle cerebral artery occlusion (pMCAO) was performed on C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA 568487 (PHA, α-7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (MLA, α-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Brain water content, the expression of monoamine oxidase B (MAO-B) and tight junction protein (claudin-5) were assessed. We found that tibia fracture increased water content in the ischemic stroke brain (p=0.006) and MAO-B positive astrocytes (p<0.001). PHA treatment reduced water content and MAO-B positive astrocytes, and increased claudin-5 expression in stroke and stroke+tibia fracture mice (p<0.05), while MLA had the opposite effect. Our findings suggest that in addition to inhibiting inflammation, activation of α-7 nAchR also reduces brain edema, possibly through diminished astrocyte oxidative stress and improved BBB integrity. Thus, the α-7 nAchR-specific agonist could be developed into a new therapy for improving recovery of patients with stroke or stroke+bone fracture.

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“…In the brain, the hippocampus is one of vulnerable regions to transient cerebral ischemia. It is widely accepted that transient cerebral ischemia leads to delayed neuronal death of pyramidal neurons in the hippocampal CA1 region in adult gerbils [3,4]. Death of the CA1 pyramidal neurons following cerebral ischemia causes a variety of neurological dysfunction such as depression and memory deficits [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Difference of fibroblast growth factor receptor 1 expression among CA1-3 regions of the gerbil hippocampus after transient cerebral ischemia

Yoo

Hwang

Lee

et al. 2010

Journal of the Neurological Sciences

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(−)Deprenyl-N-oxide, a (−)deprenyl metabolite, is cytoprotective after hypoxic injury in PC12 cells, or after transient brain ischemia in gerbils

Cited by 10 publications

References 23 publications

Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes

Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes

Activation of Alpha-7 Nicotinic Acetylcholine Receptor Reduces Brain Edema in Mice with Ischemic Stroke and Bone Fracture

Difference of fibroblast growth factor receptor 1 expression among CA1-3 regions of the gerbil hippocampus after transient cerebral ischemia

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