Antioxidant compounds protect dopamine neurons from death due to oxidative stress in vitro.
Using tissue culture models of oxidative stress caused by serum deprivation or MPTP/MPP+ toxicity, the present study establishes that the antioxidants epigallocatechin gallate, lazaroids U74389G and U83836E, reservatrol, MnTBAP, MCI 186, trolox, and melatonin protect 68-100% of dopamine (DA) neurons from cell death. In contrast, the nitric oxide inhibitor LY83583, the caspase inhibitors Z-VAD-FMK, Ac-DQMD-CHO and Z-DEVD-FMK, and the CDK-5 inhibitor, roscovotine were not neuroprotective, although death was often delayed by 1 day in vitro. We conclude that antioxidants are more effective at preventing cell death in vitro than are inhibitors at later stages in the death cascade.
Stull
Natalie D
ND
Department of Neurology, Thomas Jefferson University Medical College, Philadelphia, PA 19107, USA.
Polan
David P
DP
Iacovitti
Lorraine
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine