Pramipexole inhibits lipid peroxidation and reduces injury in the substantia nigra induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 mice.
Pramipexole has been showed to protect cultured dopaminergic (DAergic) cells against free radical-induced cytotoxicity. To test if pramipexole is protective against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-mediated nigral DAergic injury in vivo and if such protection is related to inhibition of lipid peroxidation, DAergic function and lipid peroxidation were determined in MPTP-treated C57BL/6 mice. We reported that MPTP administration induced a 38.1% increase of lipid peroxidation product thiobarbituric acid reactive substance (TBARS) in nigra, a 46.7% decrease of tyrosine hydroxylase -positive nigral DAergic neurons and a 59.4% reduction of striatal DA levels. However, pramipexole treatment significantly inhibited the TBARS production by 76%, and attenuated the MPTP-induced decreases in nigral DAergic neurons and striatal DA levels by about 50%. This study suggests that pramipexole can inhibit free radical-mediated lipid peroxidation and protect MPTP-induced nigral injury.
Zou
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Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, One Baylor Plaza, Houston, TX 77030, USA.
Xu
J
J
Jankovic
J
J
He
Y
Y
Appel
S H
SH
Le
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D052160:Benzothiazoles; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D018491:Dopamine Agonists / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000077487:Pramipexole; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D052160:Benzothiazoles; D015259:Dopamine Agents; D018491:Dopamine Agonists; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances; D000077487:Pramipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine