<i>In Vivo</i> Generation of Hydroxyl Radicals and MPTP‐Induced Dopaminergic Toxicity in the Basal Ganglia

Chiueh, Chuang C.; Wu, Ruey‐Meei; Mohanakumar, Kochupurackal P.; Sternberger, L. M.; Krishna, Gopal; Obata, Toshio; Murphy, Dennis L.

doi:10.1111/j.1749-6632.1994.tb21786.x

Cited by 110 publications

(28 citation statements)

References 24 publications

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“…[29] In a study conducted by Chiueh et al, it was also demonstrated that DMSO suppressed generation of free radicals in cranial trauma. [30] In the current study, PMNL infiltration was eliminated from white matter of group given DMSO. It was observed that TAS level was significantly higher in comparison with SCI group.…”

Section: (A) (B) (C)mentioning

confidence: 86%

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Efficiacy Of Resveratrol And Quercetin After Experimental Spinal Cord İnjury

Çiftçi

Vural

et al. 2016

Ulus Travma Acil Cerrahi Derg

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Section: (A) (B) (C)mentioning

confidence: 86%

“…As noted by Albin et al (1986) and Chiueh et al (1994) with studies published in the literature, it is believed that the increase was secondary to free radical scavenging effects of DMSO. [30,31] Moreover, increased PON-1 activity may be related to effect of DMSO on lipid metabolism.…”

Section: (A) (B) (C)mentioning

confidence: 99%

Efficiacy Of Resveratrol And Quercetin After Experimental Spinal Cord İnjury

Çiftçi

Vural

et al. 2016

Ulus Travma Acil Cerrahi Derg

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“…Our previous in vivo data also indicate that selegiline protects A9 dopaminergic nigral neurons from oxidative injury caused by MPP ϩ , the toxic metabolite of MPTP (Wu et al, 1995). It has been shown to increase levels of reactive oxygen species, such as reactive hydroxyl radicals, which can react with polyunsaturated fatty acids to generate peroxyl lipid radicals, and the related toxic species, malondialdehyde and 4-hydroxy-2,3-nonenal (Chiueh et al, 1994;Rauhala et al, 1998). Malondialdehyde reacts with amino acids to form a fluorescent complex that is a reliable marker for lipid peroxidation.…”

Section: Induction Of Trx By (؊)-Deprenyl 1411mentioning

confidence: 95%

Role of the Redox Protein Thioredoxin in Cytoprotective Mechanism Evoked by (-)-Deprenyl

et al. 2005

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Through the inhibition of monoamine oxidase type B (MAO-B), (Ϫ)-deprenyl (selegiline) prevents the conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP ϩ ) and also prevents the neurotoxicity in the dopaminergic neurons in animal models. Cumulative observations suggest that selegiline may also protect against MPP ϩ -induced neurotoxicity, possibly through the induction of pro-survival genes. We have observed that thioredoxin (Trx) mediates the induction of mitochondrial manganese superoxide dismutase (MnSOD) and Bcl-2 during preconditioning-induced hormesis. We therefore investigated whether the redox protein Trx plays any role in the neuroprotective mechanism of selegiline against MPP ϩ -induced cytotoxicity in human SH-SY5Y neuroblastoma cells and also in primary neuronal cultures of mouse midbrain dopaminergic neurons. After confirming that selegiline protects against MPP ϩ -induced cytotoxicity, we observed further that selegiline, at 1 M or less, induced Trx for protection against oxidative injury caused by MPP ϩ . The induction of Trx was blocked by protein kinase A (PKA) inhibitor and mediated by a PKAsensitive phospho-activation of mitogen-activated protein (MAP) kinase Erk1/2 and the transcription factor c-Myc. Selegiline-induced Trx and associated neuroprotection were concomitantly blocked by the antisense against Trx mRNA, but not the sense or antisense mutant phosphothionate oligonucleotides, not only in human SH-SY5Y cells but also in mouse primary neuronal culture of midbrain dopaminergic neurons. Furthermore, the redox cycling of Trx may mediate the protective action of selegiline because the inhibition of Trx reductase by 1-chloro-2,4-dinitrobenzene ameliorated the effect of selegiline. Trx (1 M) consistently increased the expression of mitochondrial proteins MnSOD and Bcl-2, supporting cell survival (Andoh et al., 2002). In conclusion, without modifying MAO-B activity, selegiline augments the gene induction of Trx, leading to elevated expression of antioxidative MnSOD and antiapoptotic Bcl-2 proteins for protecting against MPP ϩ -induced neurotoxicity.(Ϫ)-Deprenyl (selegiline) was originally developed in Hungary (for review, see Knoll, 2000) and pharmacologically classified as a selective monamine oxidase type B (MAO-B) inhibitor with a broad spectrum in clinical uses including antiparkinsonian and antidepressant activities (Birkmayer et al., 1983;Murphy et al., 1983). The initial use of selegiline in patients with Parkinson's disease is aimed at increasing brain dopamine levels through the inhibition of MAO-mediated oxidative deamination of dopamine during the treatment of patients with levodopa. Clinical observations imply that selegiline might have additional neuroprotective properties reflected by slowing the progression in clinical deterioration LeWitt, 1991). Subsequent clinical trials of selegiline in the DATATOP Parkinson study and in Alzheimer's dementia indicate that this elusive neuroprotective effect of...

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“…MPP + has been reported to inhibit complex-I in the mitochondria [4], resulting in the formation of hydroxyl radicals ( • OH) [5]. Systemic or intracranial administrations respectively of MPTP or MPP + have been reported to cause increase in • OH generation in the brain [6,7]. Intranigral, intrastriatal or intra median forebrain bundle administration of this neurotoxin would cause damage to SNpc neurons as evidenced by striatal DA depletion [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Evidence for Hydroxyl Radical Scavenging Action of Nitric Oxide Donors in the Protection Against 1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats

et al. 2007

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In the present study we provide evidence for hydroxyl radical (*OH) scavenging action of nitric oxide (NO*), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO* donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro *OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced *OH production in the mitochondria. We also tested whether co-administration of NO* donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced *OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in *OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO*, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of *OH in the nigrostriatal degeneration caused by MPP+, indicate the *OH scavenging ability of NO*, and demonstrate protection by NO* donors against MPP+-induced dopaminergic neurotoxicity in rats.

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In Vivo Generation of Hydroxyl Radicals and MPTP‐Induced Dopaminergic Toxicity in the Basal Ganglia

Cited by 110 publications

References 24 publications

Efficiacy Of Resveratrol And Quercetin After Experimental Spinal Cord İnjury

Efficiacy Of Resveratrol And Quercetin After Experimental Spinal Cord İnjury

Role of the Redox Protein Thioredoxin in Cytoprotective Mechanism Evoked by (-)-Deprenyl

Evidence for Hydroxyl Radical Scavenging Action of Nitric Oxide Donors in the Protection Against 1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats

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