Effect of melatonin and metabolites on copper-mediated oxidation of flow density lipoprotein.
OBJECTIVE
A prophylactic use of melatonin as an anti-ageing drug has recently gained public interest due to its radical scavenging property in vitro. The present study was designed to investigate a possible antiatherogenic effect of melatonin and its physiological metabolites by examining their action on the radical-initiated formation of oxidized LDL, which is known to possess a high atherogenic potency. The metabolites investigated were the precursors serotonin and N-acetyl-serotonin and the main breakdown product 6-hydroxymelatonin.


METHODS
The effect of the test substances on the in vitro oxidation of LDL (increase in conjugated diene formation) was investigated at concentrations of 1, 5, and 10 microM.


RESULTS
Melatonin increased the lag time of formation of oxidized LDL only at a concentration of 10 microM. In contrast, 6-hydroxymelatonin, serotonin and N-acetylserotonin as well as vitamin E showed inhibitory effects starting at 1 microM. Thus the antioxidative action of melatonin was negligible compared with the effect of its main metabolite, its precursors and of vitamin E.


CONCLUSIONS
The present results indicate that the pineal hormone melatonin appears to have little antiatherogenic property as regards the oxidation of LDL. Its main breakdown product 6-hydroxymelatonin, however, inhibits LDL-oxidation comparable to vitamin E. The precursors of melatonin, N-acetyl-serotonin and serotonin may also play a role in the inhibition of LDL oxidation in vivo.
Seegar
H
H
Dept. OB/GYN, University Tübingen, Germany.
Mueck
A O
AO
Lippert
T H
TH
D000328:Adult; D003300:Copper / Q000737:chemistry*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000302:isolation & purification; D008550:Melatonin / Q000031:analogs & derivatives* / Q000737:chemistry*; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000737:chemistry
D008077:Lipoproteins, LDL; D014810:Vitamin E; D003300:Copper; D008550:Melatonin; C029892:cupric chloride; C012365:6-hydroxymelatonin