Effect of methyl derivatives of dopamine on tumor necrosis factor alpha and lipid peroxidation.

We recently demonstrated that melatonin, N-acetylserotonin (NAS), and N-acetyldopamine (NAD) attenuate the synthesis of lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) and the generation of oxidant radicals. In this study, we examined whether acetyl and methyl derivatives of dopamine modulate LPS-stimulated TNF-alpha synthesis and LPS- and iron-induced lipid peroxidation. Differentiated THP-1-derived human monocytes were coincubated with Escherichia coli and rising concentrations of NAS, NAD, N-methyldopamine (NMD), or 4-O-methyldopamine (4-O-MD). After 24 h, TNF-alpha was measured in cell supernatants. In addition, lipid peroxidation was induced by adding FeCl(2) solution to mouse brain tissue homogenates in the presence of rising concentrations of NAS, NAD, NMD, or 4-O-MD. Incubating THP-1-derived monocytes with rising concentrations of NAS, NAD, NMD, or 4-O-MD markedly decreased LPS-stimulated TNF-alpha production, which was dose dependent and on the order of 96%-98%. Rising concentrations of NMD markedly inhibited lipid peroxidation by 59%-98%. Our results indicated that the inhibitory effect of NAS, NAD, NMD, or 4-O-MD on LPS-induced TNF-alpha production and FeCl(2)-stimulated lipid peroxidation is robust and dose dependent.