Effect of melatonin and metabolites on copper‐mediated oxidation of low density lipoprotein

Abstract

Aims 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 mm. Results Melatonin increased the lag time of formation of oxidized LDL only at a concentration of 10 mm. In contrast, 6-hydroxymelatonin, serotonin and N-acetylserotonin as well as vitamin E showed inhibitory effects starting at 1 mm. 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.

A novel LC–MS/MS assay for the simultaneous determination of melatonin and its two major metabolites, 6-hydroxymelatonin and 6-sulfatoxymelatonin in dog plasma: Application to a pharmacokinetic study

“…The total plasma concentration of 6-O-MEL and S-O-MEL was >30-fold higher than that of MEL in volunteers after administration of 25 mg MEL [11]. Pharmacological study revealed that 6-O-MEL exhibited stronger antiatherogenic property than MEL by inhibition of oxidation of low density lipoprotein (LDL) [12]. Although the bioactivities of S-O-MEL remained unclear, it could be hydrolyzed to 6-O-MEL by sulfatases existing broadly in the tissues of mammals.…”

N-Acetylserotonin and 6-Hydroxymelatonin against Oxidative Stress: Implications for the Overall Protection Exerted by Melatonin

“…13 It was also reported that NAS is more efficient than melatonin for protecting against iron induced lipid peroxidation, 14,15 and copper-mediated oxidation of low density lipoproteins. 8 6OHM is the major hepatic metabolite and photodegradation product of melatonin. It is described as being efficient for protecting against oxidative damage induced by UV irradiation.…”

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

“…MLT = Melatonin; MLT W+ = melatonyl radical cation; AFMK = N 1 -acetyl-N 2 -formyl-5-methoxykynuramine. [54,55]. Thus, the antioxidative activity of melatonin can be considered as a cascade reaction.…”