Monoamine metabolism provides an antioxidant defense in the brain against oxidant- and free radical-induced damage.
We propose that the brain monoamine metabolism is one of the protective systems against oxidant- and free radical-induced damage in brain. In the present study, we show that norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) protect brain homogenate and mitochondria against iron-dependent lipid peroxidation and protect brain microsomes against both iron-dependent and iron-independent lipid peroxidation. These compounds protect deoxyribose and benzoate against free radical-induced degradation and aromatic hydroxylation. Electron spin resonance studies show that the monoamines are excellent scavengers or inhibitors of 1,1-diphenyl-2-picryl hydrazyl radicals in organic solution, of superoxide and hydroxyl radicals in aqueous solution, and of carbon-centered radicals induced by iron ions in brain homogenate. Pro-oxidant properties were found in Fe(II)-H2O2-induced glutamic acid and 2-aminobutyric acid degradation, and confirmed in Fe(III)-bleomycin-dependent DNA degradation in a biphasic manner. The above effects are approximately in the order of NE = DA = 5-HT; DA > DOPAC > HVA; and 5-HT > 5-HIAA. Related supportive and contrary observations and hypotheses are discussed. Attempts are also made to briefly interpret some experimental and clinical observations.
Liu
J
J
Department of Neuroscience, Okayama University Medical School, Japan.
Mori
A
A
D000613:Aminobutyrates / Q000378:metabolism; D000818:Animals; D000975:Antioxidants; D001555:Benzene Derivatives / Q000494:pharmacology; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D015306:Biogenic Monoamines / Q000378:metabolism* / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D003855:Deoxyribose / Q000378:metabolism; D005609:Free Radicals; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006900:Hydroxylation; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000613:Aminobutyrates; D000975:Antioxidants; D001555:Benzene Derivatives; D001565:Benzoates; D015306:Biogenic Monoamines; D005609:Free Radicals; D005971:Glutamates; D001761:Bleomycin; D018698:Glutamic Acid; D003855:Deoxyribose; C012223:alpha-aminobutyric acid; D019817:Benzoic Acid; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron; C007164:cumene hydroperoxide