Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine-induced parkinsonian models in rats and dopaminergic cell cultures

Abstract In the present study, we examined the ability of a flavonoid quercetin to prevent 6-hydroxydopamine (6-OHDA)-induced oxygen radical formation and cytotoxicity in vitro and neurotoxicity in vivo. Quercetin (10–100 μM) had an acute significant antioxidant effect against the 6-OHDA-induced (30...

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Published in:	Brain research Vol. 1203; pp. 149 - 159
Main Authors:	Kääriäinen, Tiina M, Piltonen, Marjo, Ossola, Bernardino, Kekki, Heli, Lehtonen, Šárka, Nenonen, Terhi, Lecklin, Anne, Raasmaja, Atso, Männistö, Pekka T
Format:	Journal Article
Language:	English
Published:	London Elsevier B.V 08-04-2008 Amsterdam Elsevier New York, NY
Subjects:	6-Hydroxydopamine Adult and adolescent clinical studies Amphetamine - pharmacology Animals Antioxidants - therapeutic use Apomorphine - pharmacology Behavior, Animal - drug effects Biological and medical sciences Cell Line, Tumor Corpus Striatum - drug effects Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disease Models, Animal Dopamine - metabolism Dose-Response Relationship, Drug Humans L-Lactate Dehydrogenase - metabolism Male Medical sciences Motor Activity - drug effects Neuroblastoma - metabolism Neurology Neuroprotection Organic mental disorders. Neuropsychology Oxidopamine Parkinson Disease - etiology Parkinson Disease - pathology Parkinson Disease - prevention & control Parkinson's disease Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Quercetin Quercetin - therapeutic use Rats Rats, Wistar Rotational behavior SH-SY5Y cells Substantia Nigra - drug effects Tetrazolium Salts Thiazoles Tyrosine 3-Monooxygenase - metabolism Neuroprotection Parkinson's disease 5-hydroxytryptamine MFB 3,4-dihydroxyphenylacetic acid 6-OHDA homovanillic acid MTT LDH methyl tetrazolium Rotational behavior reactive oxygen species CMC SN substantia nigra DOPAC lactate dehydrogenase tyrosine hydroxylase 6-hydroxydopamine HVA 5-hydroxyindoleacetic acid PD medial forebrain bundle TH carboxymethylcellulose 5-HIAA SH-SY5Y cells ROS Quercetin 5-HT 6-Hydroxydopamine Animal model Rat Protective factor Parkinson disease Oxidopamine Flavonoid Polyphenol Degenerative disease Behavior Nervous system diseases Dopamine Rodentia Catecholamine In vitro Cerebral disorder Vertebrata Mammalia Animal Central nervous system disease Neurotransmitter Extrapyramidal syndrome
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Summary:	Abstract In the present study, we examined the ability of a flavonoid quercetin to prevent 6-hydroxydopamine (6-OHDA)-induced oxygen radical formation and cytotoxicity in vitro and neurotoxicity in vivo. Quercetin (10–100 μM) had an acute significant antioxidant effect against the 6-OHDA-induced (30 μM) oxygen radical formation in catecholaminergic SH-SY5Y neuroblastoma cells. Moreover, in these cells, quercetin at 10–50 μM had a significant protective effect against 6-OHDA though at 100 μM it was itself harmful to the cells. The possible effect of quercetin in preventing neurotoxicity in unilateral medial forebrain bundle (full nigral lesion) or striatal (partial lesion) 6-OHDA rat lesion models of Parkinson's disease was studied in three treatment schedules: a 7-day pre- or post-treatment or their combination. Rotational responses to apomorphine (0.1 mg/kg, subcutaneously) and d -amphetamine (2.5 mg/kg, intraperitoneally) were assessed at weeks 1 and 2 post-lesion. Quercetin had no consistent neuroprotective effect in either model at 50–200 mg/kg once a day or 100 mg/kg twice a day. Furthermore, no protection was observed in tyrosine hydroxylase positive nigral cell numbers, striatal fiber density or in striatal levels of dopamine. These in vitro and in vivo results cast doubt on the theory that quercetin exerts reliable neuroprotective effects against 6-OHDA-induced toxicity. In vitro, quercetin seems to be protective at low doses but damaging at high doses.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-8993 1872-6240
DOI:	10.1016/j.brainres.2008.01.089