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Brain Res Mol Brain Res. 2001 Sep 10;93(1):1-7.

3,4-Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: possible role in Parkinson's disease pathogenesis.

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  • 1Department of Chemistry, Veterans Affairs Medical Center and St. Louis University Medical School, St. Louis, MO 63110, USA.

Abstract

3,4-Dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), the monoamine oxidase (MAO) metabolites of dopamine (DA) and norepinephrine (NE), respectively, are toxic to catecholamine (CA) neurons in vitro and in vivo. DOPEGAL generates a free radical and activates mitochondrial permeability transition, a mechanism implicated in neuron death. To determine if DOPAL and other DA metabolites generate the hydroxyl radical in the presence of H(2)O(2), we used HPLC-EC to detect salicylate hydroxylation products. To determine the relative reducing capacity of DOPAL and DOPEGAL we used cyclic voltammetry to measure their reduction potentials. Results indicate that DOPAL, but not DOPEGAL, DA or other DA metabolites, generates hydroxyl radicals. Atomic absorption spectroscopy and heavy metal screening indicate that this result is not due to contamination of DOPAL with iron or other heavy metals. DOPAL reduction potential (161 mV) is lower than that of DOPEGAL (235 mV). DOPAL is present in human substantia nigra. The implications of these findings to CA neuronal death in degenerative brain diseases are discussed.

PMID:
11532332
[PubMed - indexed for MEDLINE]
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