Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Abstract

Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H₂O₂), hydroxyl radical (HO·), nitric oxide (NO·), peroxynitrite anion (ONOO^–), hypochlorous acid (HOCl), singlet oxygen (¹O₂), superoxide anion (O₂^–·) and peroxyl radical (LOO·), although the validity of its ability to scavenge O₂^–· and LOO· is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO·. Also, its secondary and tertiary metabolites, for example, N¹-acetyl-N²-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

“…However, melatonin does not undergo redox cycling, i.e. repeated oxidation and reduction, but is instead a terminal or suicidal antioxidant [27].…”

Melatonin, mitochondria, and cellular bioenergetics

“…Collectively, the data demonstrate that melatonin efficiently counteracts oxygen radical pathology. The antioxidant properties of melatonin involve its scavenging of HO , NO, ONOO − , and possibly O 2 − Tan et al, 2000a]. Also of importance, melatonin was recently shown to scavenge H 2 O 2 , the precursor of the HO , which is formed during normal metabolism of mitochondria [Tan et al, 2000a,b].…”

“…Melatonin interacts with microsomal membranes to maintain membrane stability, an effect that may improve ETC activity. Melatonin also directly scavenges H 2 O 2 , which is abundantly produced in mitochondria from O 2 − [Tan et al, 2000a]. Thus, melatonin improves ETC and reduces mitochondrial oxidative damage.…”

Regulatory roles of serotonin and melatonin in abiotic stress tolerance in plants

“…27 It helps in the detoxification of several ROS and RNS (reactive nitrogen species), such as the hydroxyl radical (OH ¡ ) hydrogen peroxide (H 2 O 2 ), peroxynitrite anion (ONOO ¡ ), nitric oxide, peroxyl radical (LOO ¡ ) and singlet oxygen ( 1 O 2 ). [28][29][30][31] Melatonin molecule consists of an electron-rich indole moiety and 2 side chain groups: 5-methoxy group and 3-amide group www.tandfonline.com e1049788-3 Plant Signaling & Behavior (Fig. 3).…”

“…32,48,49 It may directly scavenge H 2 O 2 and help in the maintenance of intracellular H 2 O 2 concentration at steady state levels. 28 This might be due to the inhibition of H 2 O 2 accumulation and enhanced catalase and POD activities by endogenous melatonin supplementation. Pretreatment with 0.1 mM melatonin stimulates SOD and CAT activities along with increased survival rate in Rhodiola crenulata cells and callus.…”