Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in the rat

Carrillo, Marı́a C.; Minami, Chiyoko; Kitani, Kenichi; Maruyama, Wakako; Ohashi, Kaoru; Yamamoto, Takako; Naoi, M; Kanai, Setsuko; Youdim, Mbh

doi:10.1016/s0024-3205(00)00643-3

Cited by 115 publications

(55 citation statements)

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“…1), shown previously to exert neuroprotective/neurorescue activities against cell death induced by a variety of insults [e.g., serum withdrawal, the neurotoxins N-morpholino sydnonimine, and N-methyl-(R)-salsolinol] Bar-Am et al, 2004;Weinreb et al, 2004). This action of the propargyl was attributed to 1) stabilization of the ⌬⌿m and prevention of permeability transition pore (Maruyama et al, 2001); 2) induction of the prosurvival protein kinase C pathway, in association with gene regulation of the Bcl-2-related protein family (Akao et al, 2002); and 3) activation of antioxidant enzymes, such as superoxide dismutase and catalase (Carrillo et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The Novel Multifunctional, Iron-Chelating Drugs M30 and HLA20 Protect Pancreatic β-Cell Lines from Oxidative Stress Damage

Mechlovich¹,

Amit²,

Mandel³

et al. 2010

J Pharmacol Exp Ther

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Increasing evidence suggests that oxidative stress (OS)-induced pancreatic ␤-cell impairments is involved in diabetes and diabetic complications. Our group has recently synthesized two multifunctional nontoxic, lipophilic, ironchelating drugs, 5-{N-methyl-N-propargylaminomethyl}-8-hydroxyquinoline (M30) and 5-{4-propargylpiperazin-1-ylmethyl}-8-hydroxyquinoline (HLA20), for the treatment of various OS-mediated pathogeneses. These compounds contain the N-propargylamine cytoprotective moiety of the antiparkinsonian drug rasagiline (Azilect) and the ironcomplexing component 8-hydroxyquinoline. The aim of this research was to evaluate the protective effect of the multifunctional iron-chelating drugs on rat insulin-producing pancreatic ␤-cells (INS-1E and RINm) against OS-induced cytotoxicity. We found that M30 and HLA20 markedly and dose-dependently inhibited H 2 O 2 -induced cytotoxicity, associated with decreased intracellular reactive oxygen species formation and increased catalase activity. In accordance, the catalase inhibitor 3-amino-1,2,4-triazol blocked the protective action of M30 against H 2 O 2 -induced damage. Both compounds significantly increased the levels of the iron-responsive protein transferrin receptor indicating their iron-chelating effect. Further mechanistic studies showed that M30 and HLA20 attenuated H 2 O 2 -induced mitochondrial membrane potential loss, decreased the release of cytochrome c into the cytoplasm, and inhibited the activation of caspase-3, suggesting that these drugs may produce cytoprotective effects via the preservation of mitochondrial function. These results indicate that the novel drugs, M30 and HLA20 display significant cytoprotective activity against OS-induced cytotoxicity in insulin producing ␤-cells, which might be of therapeutic use in the treatment of diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

The Novel Multifunctional, Iron-Chelating Drugs M30 and HLA20 Protect Pancreatic β-Cell Lines from Oxidative Stress Damage

Mechlovich¹,

Amit²,

Mandel³

et al. 2010

J Pharmacol Exp Ther

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“…Sham: Thoracotomy without MI induction or any treatment, RG: MI and RG, 2.0 mg/kg/day, N/S: MI and normal saline (N/S) 0.9%/day. RG or N/S was administered by intraperitoneal injections,19, 20 for 28 days, beginning 24 h post‐MI.…”

Section: Methodsmentioning

confidence: 99%

The neuroprotective agent Rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

Varela¹,

Mavroidis

Katsimpoulas³

et al. 2017

ESC Heart Failure

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AimRasagiline mesylate (N‐propargyl‐1 (R)‐aminoindan) (RG) is a selective, potent irreversible inhibitor of monoamine oxidase‐B with cardioprotective and anti‐apoptotic properties. We investigated whether it could be cardioprotective in a rat model undergoing experimental myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery.Methods and resultsRG was administered, intraperitoneally, for 28 days (2 mg/kg) starting 24 h after MI induction. Echocardiography analysis revealed a significant reduction in left ventricular end‐systolic and diastolic dimensions and preserved fractional shortening in RG‐treated compared with normal saline group at 28 days post‐MI (31.6 ± 2.3 vs. 19.6 ± 1.8, P < 0.0001), respectively. Treatment with RG prevented tissue fibrosis as indicated by interstitial collagen estimation by immunofluorescence staining and hydroxyproline content and attenuated the number of apoptotic myocytes in the border zone (65%) as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Caspase 3 relative protein levels were significantly decreased in the non‐infarcted myocardium. Markedly decreased malondialdehyde levels in the border zone indicate a reduction in tissue oxidative stress.ConclusionsOur study demonstrates a positive effect of RG in the post‐MI period with a significant attenuation in cardiac remodelling.

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“…In order to preserve brain dopamine, it is also common to treat patients with a monoamine oxidase B (MAO-B) inhibitor. 4 Selegiline (L-Deprenyl) and Rasagiline ( Figure 1) [5][6][7][8][9][10] are selective inhibitors of MAO-B and Selegiline is currently used for the treatment of Parkinson's and Alzheimer's diseases. This compound was reported to have a neuroprotective activity due to the prevention of apoptosis.…”

Section: 3mentioning

confidence: 99%

Synthesis of Deprenyl-like nitroxide free radicals and their diamagnetic derivatives

Sár¹,

Kálai²,

Jekő³

et al. 2011

Arkivoc

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Synthesis of paramagnetically modified deprenyl and oxotremorine is reported. Starting from 5-and 6-membered 2,5-disubstituted nitrones 1, 6 or 4-phenyl-2,5,5-trimethyl-1H-pyrroline 1-oxide 11 deprenyl or oxotremorine like nitroxides were synthesized via Grignard reactions. The corresponding pre-nitroxides with propargylamine structure were achieved by reduction of nitroxides followed by methylation.

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Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in the rat

Cited by 115 publications

References 0 publications

The Novel Multifunctional, Iron-Chelating Drugs M30 and HLA20 Protect Pancreatic β-Cell Lines from Oxidative Stress Damage

The Novel Multifunctional, Iron-Chelating Drugs M30 and HLA20 Protect Pancreatic β-Cell Lines from Oxidative Stress Damage

The neuroprotective agent Rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

Synthesis of Deprenyl-like nitroxide free radicals and their diamagnetic derivatives

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