Quantification of the water/lipid affinity of melatonin and a pinoline derivative in lipid models

Abstract

This study assessed the location of melatonin (N-acetyl-5-methoxytryptamine) and of a pinoline derivative (GWC22) [6-ethyl-1-(3-methoxyphenyl)-2-propyl-1,2,3,4-tetrahydro-beta-carboline], when present in lipid assemblies such as linoleate micelles, phosphatidylcholine liposomes or low density lipoproteins (LDL). The efficiency of radical scavenging by these compounds is highly dependent on their partitioning between the lipidic and aqueous phases. We determined the proportion of melatonin or GWC22 in the aqueous and lipid phases of each system (concentrations of the antioxidants ranging between 3 x 10(-5) and 10(-4) m) by assaying melatonin or GWC22 by HPLC/UV detection, or by fluorescence for melatonin in micelles. Our results show that melatonin and GWC22 were preferentially located in the aqueous phase of micelles (68.4% and 59.0%, respectively), whereas only 30.5% of melatonin and 39.0% of GWC22 were found in the lipid phase. By contrast, in phosphatidylcholine liposomes, both compounds were essentially present in the lipid phase (73.5% for melatonin and 79.1% for GWC22, versus 25.9% and 19.5% in the aqueous phase, respectively). In the case of LDL, 99.9% of the melatonin added was found in the methanol/water extracting phase containing phospholipids, unesterified cholesterol and apolipoprotein B100. The partitioning of melatonin and GWC22 in linoleate micelles gave new insights on the marked protective effect of GWC22 towards radiation-induced lipid peroxidation and allowed us to determine more accurately the lower limit values of the reaction rate constants of the two molecules studied with lipid peroxyl radicals, i.e. k(LOO.+melatonin)) >or= 9.0 x 10(4)m(-1)s(-1) and k(LOO.+GWC22) >or= 3.5 x 10(5)m(-1)s(-1).

Melatonin enhances antioxidant action of α-tocopherol and ascorbate against NADPH- and iron-dependent lipid peroxidation in human placental mitochondria

“…Melatonin seemingly acts inside mitochondrial membranes to interrupt the chain reaction of lipid peroxidation. This conclusion also is supported by data reported previously where it has been proved that melatonin can react with lipid peroxyl radicals and that reaction occurs in media without metal ions [6,30,31]. Melatonin also reacts with another important component of lipid peroxidation -alkoxyl radical with high velocity [2,32].…”

Melatonin: Action as antioxidant and potential applications in human disease and aging

“…The efficiency of radical scavenging by melatonin is therefore highly dependent on its partitioning between the lipidic and aqueous phases. In order to better assess the location of melatonin in lipid systems, Mekhloufi et al (2007) used model assemblies such as linoleate micelles, phosphatidylcholine liposomes or LDL. The proportion of melatonin in the aqueous and lipid phases of each system has been determined (concentrations of the antioxidants ranging between 3 × 10 −5 and 10 −4 M) by assaying melatonin by HPLC/UV detection in liposomes and LDL, or by fluorescence in micelles.…”

Antioxidant activity of benzoxazolinonic and benzothiazolinonic derivatives in the LDL oxidation model

“…16 This compound has been shown to display better antioxidant properties than melatonin toward peroxyl-induced peroxidation of a linoleate model system. [17][18][19] 6-Methoxy-2-benzoxazolone (6-MBAO) was described in the literature as exhibiting an antioxidative potency similar to that of melatonin. 20 Both the structures, GWC22 and 6-methoxy-2-benzoxazolinone, allowed to design a new family of benzoxazolinonic and benzothiazolinonic derivatives with potent antioxidant activities (Fig.…”