Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine-induced parkinsonian models in rats and dopaminergic cell cultures.
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 microM) had an acute significant antioxidant effect against the 6-OHDA-induced (30 microM) oxygen radical formation in catecholaminergic SH-SY5Y neuroblastoma cells. Moreover, in these cells, quercetin at 10-50 microM had a significant protective effect against 6-OHDA though at 100 microM 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.
Kääriäinen
Tiina M
TM
Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627 (Yliopistonranta 1C), FIN-70211 Kuopio, Finland. Tiina.Kaariainen@uku.fi
Piltonen
Marjo
M
Ossola
Bernardino
B
Kekki
Heli
H
Lehtonen
Sárka
S
Nenonen
Terhi
T
Lecklin
Anne
A
Raasmaja
Atso
A
Männistö
Pekka T
PT
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism; D016627:Oxidopamine; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D016627:Oxidopamine; D011794:Quercetin; D000661:Amphetamine; D007770:L-Lactate Dehydrogenase; D014446:Tyrosine 3-Monooxygenase; C022616:thiazolyl blue; D001058:Apomorphine; D004298:Dopamine