Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures.
Naturally occurring polyphenols have the potential to prevent oxidative damage in various pathophysiological conditions. Various members of the flavonoid family were investigated to determine if they could protect mesencephalic dopamine (DA) neurones from injury and reduce apoptosis produced by oxidative stressors. Primary mesencephalic cultures were sensitive to oxidative insults (hydrogen peroxide, 4-hydroxynonenal, rotenone, 6-hydroxydopamine and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium hydrochloride (MPP+)) which produced concentration-dependent decreases in cellular viability across an apoptotic-necrotic continuum of injury. Flavonoids (catechin, quercetin, chrysin, puerarin, naringenin, genestein) protected mesencephalic cultures from injury by MPP+, which was shown by DNA fragmentation studies and tyrosine hydroxylase (TH) immunocytochemistry of DA neurones to occur by apoptosis. Catechin also reduced injury produced by hydrogen peroxide, 4-hydroxynonenal, rotenone and 6-hydroxydopamine as shown by increases in cellular viability and [3H]DA uptake. When the neuroprotection of catechin against MPP+-induced injury was compared to that produced by the caspase-3 inhibitor, Z-DVED-FMK, both reduced DNA fragmentation and the injury patterns of TH-positive neurones. These data demonstrate the neuroprotective abilities of flavonoids which are able to attenuate the apoptotic injury of mesencephalic DA neurones. Since these DA neurones are under oxidative stress in Parkinsonism, our findings suggest that flavonoids could provide benefits along with other anti-oxidant therapies in Parkinson's disease.
Mercer
Linda D
LD
Department of Pharmacology, Monash University, Clayton, Vic. 3800, Australia. l.mercer@hfi.unimel.edu.au
Kelly
Belinda L
BL
Horne
Malcolm K
MK
Beart
Philip M
PM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D004298:Dopamine