Effect of Methyl Derivatives of Dopamine on Tumor Necrosis Factor ? 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-? (TNF-?) and the generation of oxidant radicals. In this study, we examined whether acetyl and methyl derivatives of dopamine modulate LPS-stimulated TNF-? synthesis and LPS- and iron-induced lipid peroxidation. Differentiated THP-1derived human monocytes were coincubated with Escherichia coli and rising concentrations of NAS, NAD, N-methyldopamine (NMD), or 4-O-methyldopamine (4-O-MD). After 24h, TNF-? was measured in cell supernatants. In addition, lipid peroxidation was induced by adding FeCl2 solution to mouse brain tissue homogenates in the presence of rising concentrations of NAS, NAD, NMD, or 4-O-MD. Incubating THP-1derived monocytes with rising concentrations of NAS, NAD, NMD, or 4-O-MD markedly decreased LPS-stimulated TNF-? 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-? production and FeCl2-stimulated lipid peroxidation is robust and dose dependent.
lipid peroxidation n-acetylserotonin n-acetyldopamine lipopolysaccharide tumor necrosis factor-? n-methyldopamine 4-o-methyldopamine malondialdehyde