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

• Published in: Brain research 2008-04, Vol.1203, p.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: Article
• Language: English
• 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
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.01.089

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.