Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical.
Melatonin and classic antioxidants possess the capacity to scavenge ABTSb+ with IC50s of 4, 11, 15.5, 15.5, 17 and 21 microm for melatonin, glutathione, vitamin C, trolox, NADH and NADPH, respectively. In terms of scavenging ABTSb+, melatonin exhibits a different profile than that of the classic antioxidants. Classic antioxidants scavenge one or less ABTSb+, while each melatonin molecule can scavenge more than one ABTSb+, probably with a maximum of four. Classic antioxidants do not synergize when combined in terms of scavenging ABTSb+. However, a synergistic action is observed when melatonin is combined with any of the classic antioxidants. Cyclic voltammetry indicates that melatonin donates an electron at the potential of 715 mV. The scavenging mechanism of melatonin on ABTSb+ may involve multiple-electron donations via intermediates through a stepwise process. Intermediates including the melatoninyl cation radical, the melatoninyl neutral radical and cyclic 3-hydroxymelatonin (cyclic 3-OHM) and N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) seem to participate in these reactions. More interestingly, the pH of the solution dramatically modifies the ABTSb+ scavenging capacity of melatonin while pH changes have no measurable influence on the scavenging activity of classic antioxidants. An acidic pH markedly reduces the ABTSb+ scavenging capacity of melatonin while an increased pH promotes the interaction of melatonin and ABTSb+. The major melatonin metabolites that develop when melatonin interacts with ABTSb+ are cyclic 3-OHM and AFMK. Cyclic 3-OHM is the intermediate between melatonin and AFMK, and cyclic 3-OHM also has the ability to scavenge ABTSb+. Melatonin and the metabolites which are generated via the interaction of melatonin with ABTSb+, i.e. the melatoninyl cation radical, melatoninyl neutral radical and cyclic 3-OHM, all scavenge ABTSb+. This unique cascade action of melatonin, in terms of scavenging, increases its efficiency to neutralized ABTSb+; this contrasts with the effects of the classic antioxidants.
Tan
Dun-xian
DX
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Hardeland
Rüdiger
R
Manchester
Lucien C
LC
Poeggeler
Burkhard
B
Lopez-Burillo
Silvia
S
Mayo
Juan C
JC
Sainz
Rosa M
RM
Reiter
Russel J
RJ
D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism; D052160:Benzothiazoles; D002412:Cations; D002839:Chromans / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism*; D005609:Free Radicals; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000378:metabolism; D019563:Mechanics; D008550:Melatonin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D009249:NADP / Q000737:chemistry / Q000378:metabolism; D013451:Sulfonic Acids
D000975:Antioxidants; D052160:Benzothiazoles; D002412:Cations; D002839:Chromans; D016166:Free Radical Scavengers; D005609:Free Radicals; D013451:Sulfonic Acids; D009243:NAD; C052611:1-acetyl-1,2,3,3a,8,8a-hexahydro-8a-hydroxy-5-methoxypyrrolo(2,3-b)indole; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D009249:NADP; D005978:Glutathione; D008550:Melatonin; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid