Effects of Estradiol, Phytoestrogens, and Ginkgo Biloba Extracts Against 1-Methyl-4-phenyl-pyridine-Induced Oxidative Stress

Gagné, B; Gélinas, Sylvie; Bureau, Geneviève; Lagacé, Bruno; Ramassamy, Charles; Chiasson, Keith; Valastro, Barbara; Martinoli, Maria-Grazia

doi:10.1385/endo:21:1:89

Cited by 25 publications

(28 citation statements)

References 50 publications

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“…As described in the introduction section, treatment with quercetin at 5-40 mM attenuated cell death induced by various causes of oxidative stress such as MPP ϩ , H 2 O 2 and b-amyloid peptides in neuronal cells including differentiated PC12 cells. 6,15,20) We found that quercetin did not protect against H 2 O 2 toxicity, but by itself caused cell death accompanied by DNA fragmentation in undifferentiated PC12 cells. The reasons for this discrepancy are not clear at present.…”

Section: Possible Mechanism Of Quercetin-induced Cell Toxicitymentioning

confidence: 90%

“…25) Quercetin showed a protective effect against MPP ϩ toxicity in differentiated, but not in undifferentiated, PC12 cells. 15) These reports may indicate that the response to quercetin differs depending on the degree of cell differentiation. In our conditions, however, quercetin caused cell death of differentiated PC12 cells.…”

Section: Possible Mechanism Of Quercetin-induced Cell Toxicitymentioning

confidence: 99%

“…12,13) Quercetin has been shown to inhibit cell death and/or apoptosis induced by various stimuli including oxidative stress and MPP ϩ in differentiated PC12 cells. [14][15][16] In undifferentiated PC12 cells, however, antioxidants including quercetin did not have a protective effect against cell death induced by oxidative stress including MPP ϩ . 15,16) The effect of quercetin on cell survival and death in undifferentiated PC12 cells has not been well established.…”

mentioning

confidence: 98%

“…[14][15][16] In undifferentiated PC12 cells, however, antioxidants including quercetin did not have a protective effect against cell death induced by oxidative stress including MPP ϩ . 15,16) The effect of quercetin on cell survival and death in undifferentiated PC12 cells has not been well established. In the present study, we investigated whether quercetin causes cell death in undifferentiated PC12 cells or not.…”

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confidence: 98%

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Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Sasaki

Nakamura

Tsuchiya

et al. 2007

Biological & Pharmaceutical Bulletin

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Flavonoids, a large group of polyphenolic compounds found in fruits and vegetables, have attracted much attention because of their broad pharmacological, particularly antioxidative, activities.1,2) Flavonoids may exert beneficial effects on a number of disease states including cancer, cardiovascular disease, inflammation and neurodegenerative disorders. 1,2)The pathology of neurodegenerative disorders including Alzheimer's disease and aging is associated with oxidative stress caused by reactive oxygen species and reactive nitrogen species.2,3) If oxidative stress is suppressed by compounds in foods, such as flavonoids, this may act as a preventive measure to reduce damage and/or disfunction of cells. Quercetin (3,3Ј,4Ј,5,, which possesses a wide spectrum of pharmacological and biological properties, 2,4) is found in many kinds of food. The daily Western diet contains on average about 25 mg of various flavonoids, of which quercetin is a major ingredient (16 mg/d).5) Quercetin can scavenge free radicals directly and inhibit the oxidation of various molecules resulting in the activation of antioxidant defense pathways in vivo and in vitro. However, the actions of flavonoids are complex and paradoxical in some cases. Several studies have shown that quercetin is a pro-oxidant and cytotoxic in leukemic cells. 7,8) Flavonoids including quercetin caused apoptosis in carcinoma/cancer cells 2,9) and showed cytotoxicity in normal cells including human umbilical vein endothelial cells.10) The neuronal density of the hippocampus in gerbils subjected to infusion of quercetin to the ventricle was significantly lower than that in control.11) Thus, the effects of quercetin on cell death and/or apoptosis in cells including neuronal cells have not been well confirmed.The PC12 cell line, a rat adrenal medullary pheochromocytoma, is a useful model for studying the survival of neuronal cells. Native PC12 cells divide and resemble precursors of adrenal chromaffin cells and sympathetic neurons when grown in the presence of serum, and gradually attain the phenotypic properties of sympathetic neurons on the addition of nerve growth factor (NGF). Previously, we reported that the treatment of native and undifferentiated PC12 cells with an inhibitor of thioredoxin reductase and dopaminergic neurotoxins such as 1-methyl-4-phenylpyridinium ion (MPP ϩ ) caused apoptosis via a caspase-mediated pathway. 12,13) Quercetin has been shown to inhibit cell death and/or apoptosis induced by various stimuli including oxidative stress and MPP ϩ in differentiated PC12 cells. [14][15][16] In undifferentiated PC12 cells, however, antioxidants including quercetin did not have a protective effect against cell death induced by oxidative stress including MPP ϩ . 15,16) The effect of quercetin on cell survival and death in undifferentiated PC12 cells has not been well established. In the present study, we investigated whether quercetin causes cell death in undifferentiated PC12 cells or not. The effect of genistein, a soy isoflavone that has the pro-apoptotic ac...

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Section: Possible Mechanism Of Quercetin-induced Cell Toxicitymentioning

confidence: 90%

Section: Possible Mechanism Of Quercetin-induced Cell Toxicitymentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 98%

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Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Sasaki

Nakamura

Tsuchiya

et al. 2007

Biological & Pharmaceutical Bulletin

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“…These observations led to the conclusion that the neuroprotective effects of 17a-E2 or 17b-E2 might be due to their antioxidant properties, although other non-genomic effects could not be excluded. Regardless, 17b-E2, 17a-E2, and the phytoestrogens quercetin and resveratrol, all protect PC12 cells against MPP1, whereas closely related molecules with less extended resonance structure, such as coumestrol, genistein, and kaempferol, do not [Gelinas and Martinoli, 2002;Gagne et al, 2003]. Despite the studies that report comparable cytoprotection by the two estradiol isomers in cell culture, only 17b-E2 has demonstrated beneficial effects in the animal models of PD, such as MPTP toxicity [Dluzen et al, 2001;Ramirez et al, 2003;Callier et al, 2000Callier et al, , 2002.…”

Section: Introductionmentioning

confidence: 98%

17β‐ and 17α‐estradiol are non‐competitive inhibitors of dopamine uptake: implications for Parkinson's disease models and therapeutics

Dykens¹,

Wersinger

Sidhu

2005

Drug Development Research

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Despite compelling literature documenting the cyto-and neuro-protective activities of various estrogens in a wide variety of cell and animal models, several large clinical trials of hormone replacement therapies have failed to detect such beneficial responses in humans. To some degree, this failure stems from profound hormonal responses that counterbalance the protective effects. This limitation could be circumvented by the development of less hormonally active estrogen analogs that retain the cytoprotective activities of the parental hormones. For example, 17a-estradiol (17a-E2) is at least 200-fold less active than 17b-estradiol (17b-E2) as a transactivating hormone, yet it is equipotent as a cytoprotectant in many cell types exposed to a variety of stressors, such as amyloid toxicity, serum withdrawal, oxidative stress, and glutamate excitotoxicity. Both estradiol isomers stabilize mitochondrial function under pathogenic conditions, and both have shown efficacy in animal models of stroke. The results for models of Parkinson's disease differ, and 17b-E2, but not 17a-E2, has been reported previously to provide neuroprotection against MPTP toxicity. However, such findings must be regarded in light of reports that 17b-E2 impedes cellular uptake of MPTP by the dopamine transporter (DAT), thereby forestalling development of the lesion rather than providing authentic cytoprotection. We report here that both 17a-E2 and 17b-E2 show classical, non-competitive, inhibition of dopamine uptake by the human DAT (hDAT) transfected into Ltk À mouse fibroblasts, HEK293 human embryonic kidney cells, and SH-SY5Y human neuroblastoma cells. IC 50 values vary slightly with cell type, but are 400 and 70 nM for 17a-E2 and 17b-E2, respectively, in SH-SY5Y cells. We also evaluated 17a-E2 in the 6-OH-dopamine (6-OHDA) model of PD, where toxin uptake occurs via the DAT. In these studies, treatment with estrogen was delayed for 6 hr after unilateral intrastriatal 6-OHDA injection to allow for toxin uptake. After 6 hr, a loading dose of 17a-E2 (100 mg/kg in sesame oil) was injected s.c., accompanied by implanting of a sustained release silastic device. After 21 days, animals treated with 17a-E2 showed significant improvements in both gait asymmetry and apo-morphine induced rotational defects. These positive results encourage evaluation of 17a-E2 in a host of neurodegenerative diseases. Drug Dev.

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Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation

Bureau

Longpré

Martinoli

2007

J of Neuroscience Research

298

181

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Parkinson's disease (PD) is a movement disorder characterized by a progressive loss of nigrostriatal dopaminergic neurons. Microglia activation and neuroinflammation have been associated with the pathogenesis of PD. Indeed, cytokines have been proposed as candidates that mediate the apoptotic cell death of dopaminergic neurons seen in PD. In this study, we investigated the effect of two natural polyphenols, resveratrol and quercetin, on neuroinflammation. For glial cells, we observed that lipopolysaccharide (LPS)-induced mRNA levels of two proinflammatory genes, interleukin 1-alpha and tumor necrosis factor-alpha, are strongly decreased by treatments with resveratrol or quercetin. We also undertook microglial-neuronal coculture to examine the influence of resveratrol and quercetin on dopaminergic neuronal cell death evoked by LPS-activated microglia. Cytotoxicity assays were performed to evaluate the percentage of cell death, with apoptotic cells identified by both the TdT-mediated dUTP nick end labeling technique and the detection of cleaved caspase-3. We report that treatment of N9 microglial cells with resveratrol or quercetin successfully reduced the inflammation-mediated apoptotic death of neuronal cells in our coculture system. Altogether our results demonstrate that resveratrol and quercetin diminished apoptotic neuronal cell death induced by microglial activation and suggest that these two phytoestrogens may be potent antiinflammatory compounds.

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Effects of Estradiol, Phytoestrogens, and Ginkgo Biloba Extracts Against 1-Methyl-4-phenyl-pyridine-Induced Oxidative Stress

Cited by 25 publications

References 50 publications

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

17β‐ and 17α‐estradiol are non‐competitive inhibitors of dopamine uptake: implications for Parkinson's disease models and therapeutics

Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation

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