Physiological neuroprotection by melatonin in a 6-hydroxydopamine model of Parkinson's disease

Sharma, Rohita; McMillan, Catherine; Tenn, Catherine; Niles, Lennard P.

doi:10.1016/j.brainres.2005.10.084

Cited by 86 publications

(65 citation statements)

References 27 publications

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“…Exposure to 6-OHDA results in the formation of ROS and RNS. It has been demonstrated that the oxidative damage induced by 6-OHDA could be prevented by treatment with antioxidants, such as melatonin (44,45). The results of the present study demonstrate that exposure to 6-OHDA significantly increases NO production and iNOS expression in PC12 cells.…”

Section: Discussionsupporting

confidence: 59%

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Lee

2011

Int J Mol Med

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Abstract.Flavonoids have been reported to be potent antioxidants and beneficial in the treatment of oxidative stress-related diseases. Quercetin, a major flavonoid naturally occurring in plants, deserves attention because of its beneficial effects observed in various in vitro and in vivo neural damage models; however, the actions of quercetin are paradoxical. In an effort to confirm the neuroprotective effect of quercetin and to elucidate its mechanism of action, the neuroprotective effects of quercetin in PC12 cells and in zebrafish models were investigated. In this study, the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), was used to induce neural damage in PC12 cells and zebrafish models. Pretreatment with quercetin offered neuroprotection against 6-OHDA-induced PC12 cell death. Moreover, quercetin could prevent 6-OHDA-induced PC12 cell apoptosis and 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. Interestingly, quercetin was able to protect, but not rescue the dopaminergic neuron damage when zebrafish were treated with quercetin at different maturation stages of the blood brain barrier. A mechanistic study showed that quercetin could inhibit NO over-production and iNOS over-expression in PC12 cells and could down-regulate the over-expression of pro-inflammatory genes (e.g. IL-1ß, TNF-· and COX-2) in zebrafish, suggesting that these genes play a role in the neuroprotective effect of quercetin. The objective of this study was to provide a scientific rationale for the clinical use of quercetin, leading to its development as an effective therapeutic agent for the treatment of Parkinson's disease.

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Section: Discussionsupporting

confidence: 59%

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Lee

2011

Int J Mol Med

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“…Delivery of melatonin at physiological doses by mini-pump also protects against a 6-OHDA-induced decrease in mitochondrial complex I activity (Dabbeni-Sala et al, 2001). Furthermore, 6-OHDA-lesioned animals treated with a high physiological dose of melatonin exhibit a significant reduction in apomorphine-induced rotational behaviour and concomitant protection of striatal TH immunoreactivity (Sharma et al, 2006). The neuroprotection promoted by melatonin is thought to involve its antioxidant and free radical scavenging effects Rodriguez et al, 2004;Vega-Naredo et al, 2005).…”

Section: Immunophilin Ligandsmentioning

confidence: 99%

Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

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“…The present study demonstrated diminished GSH-Px, SOD and CAT activity in MPTP-treated mice compared to salinetreated mice. Similarly, the SNpc of PD brains has a reduced level of the antioxidant enzymes such as CAT, SOD and GSH-Px [49] and antioxidant molecules such as GSH [50], suggesting the presence of a sustained burden of oxidative stress that overwhelmed the antioxidant capacity.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown, in rat brain cortex, that melatonin administration increases MnSOD Cu/Zn SOD, GSH-Px and CAT mRNA levels [30]. Melatonin treatment immediately post-surgery attenuates dopaminergic denervation in the 6-OHDAlesioned rat striatum when administered at physiological concentrations [49]. Melatonin has been reported to induce antioxidant enzymes such as SOD [26] and GSH-Px activities, to prevent oxidative damage [43] and protect against clomiphene citrateinduced generation of H 2 O 2 in rat eggs [55].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant potential of melatonin enhances the response to L-dopa in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice

Zaitone

Hammad

Farag

2013

Pharmacological Reports

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Abstract:Background: Parkinson's disease is a neurodegenerative disorder of uncertain pathogenesis characterized by a loss of dopaminergic neurons in substantia nigra pars compacta, and can be modeled by the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The current research was directed to investigate the role of melatonin in preventing the gradual decrease in the response to L-dopa in MPTP-induced parkinsonism in mice. Methods: Eighty four male Swiss mice were divided into seven groups. Group I is the saline group. The other six groups were injected with MPTP (20 mg/kg/2 h). Group II is the MPTP control group. Group III was treated with L-dopa/carbidopa (100/10 mg/kg, po). Group IV and V were treated with melatonin (5 or 10 mg/kg, po), respectively. Group VI and VII received L-dopa/carbidopa in combination with melatonin in the same above-mentioned doses, respectively. Results: Results showed that MPTP-treated mice exhibited low striatal dopamine level accompanied by motor impairment and increased oxidative stress. Treatment with L-dopa improved the motor performance of mice. Addition of melatonin to L-dopa therapy improved the motor response to L-dopa and increased striatal dopamine level. This combination reduced lipid peroxidation, ameliorated reduced glutathione and improved antioxidant enzyme activities (p £ 0.05). Conclusions: Overall, our study suggests that the antioxidant potential of melatonin makes it a promising candidate to L-dopa in treating Parkinson's disease.

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Physiological neuroprotection by melatonin in a 6-hydroxydopamine model of Parkinson's disease

Cited by 86 publications

References 27 publications

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

Driving GDNF expression: The green and the red traffic lights

Antioxidant potential of melatonin enhances the response to L-dopa in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice

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