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 TEARS 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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.