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3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in PC12 Cells.

Abstract
The catecholaldehyde hypothesis predicts that monoamine oxidase (MAO) inhibition should slow the progression of Parkinson's disease, by decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). Inhibiting MAO, however, diverts the fate of cytoplasmic dopamine toward potentially harmful spontaneous oxidation products, indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels. 3,4-Dihydroxyphenylethanol (hydroxytyrosol) is an abundant anti-oxidant phenol in constituents of the Mediterranean diet. Whether hydroxytyrosol alters enzymatic or spontaneous oxidation of dopamine has been unknown. Rat pheochromocytoma PC12 cells were incubated with hydroxytyrosol (10 µM, 180 min) alone or with the MAO-A inhibitor clorgyline (1 nM) or the MAO-B inhibitors rasagiline or selegiline (0.5 µM). Hydroxytyrosol decreased levels of DOPAL by 30 % and Cys-DA by 49 % (p < 0.0001 each). Co-incubation with hydroxytyrosol prevented the increases in Cys-DA seen with all 3 MAO inhibitors. Hydroxytyrosol therefore inhibits both enzymatic and spontaneous oxidation of endogenous dopamine and mitigates the increase in spontaneous oxidation during MAO inhibition.
AuthorsDavid S Goldstein, Yunden Jinsmaa, Patti Sullivan, Courtney Holmes, Irwin J Kopin, Yehonatan Sharabi
JournalNeurochemical research (Neurochem Res) Vol. 41 Issue 9 Pg. 2173-8 (Sep 2016) ISSN: 1573-6903 [Electronic] United States
PMID27220335 (Publication Type: Journal Article)
Chemical References
  • Dopamine Agents
  • Monoamine Oxidase Inhibitors
  • 3,4-Dihydroxyphenylacetic Acid
  • 3,4-dihydroxyphenylethanol
  • 3,4-dihydroxyphenylacetaldehyde
  • Monoamine Oxidase
  • Phenylethyl Alcohol
  • Dopamine
Topics
  • 3,4-Dihydroxyphenylacetic Acid (analogs & derivatives, metabolism)
  • Animals
  • Dopamine (metabolism)
  • Dopamine Agents (pharmacology)
  • Monoamine Oxidase (metabolism)
  • Monoamine Oxidase Inhibitors (pharmacology)
  • Oxidation-Reduction (drug effects)
  • PC12 Cells
  • Parkinson Disease (drug therapy, metabolism)
  • Phenylethyl Alcohol (analogs & derivatives, pharmacology)
  • Rats

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