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.