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

Abstract

Human placental mitochondria might be a significant source of NADPH- and iron-dependent production of reactive oxygen species (ROS). Preeclampsia is believed to be a consequence of overproduction of ROS in human placenta. The experimental results presented here show that melatonin inhibits NADPH- and iron-dependent lipid peroxidation of human placental mitochondria in a concentration-dependent manner. At 1.5 mm concentration, melatonin suppressed this process nearly completely. Melatonin does not influence significantly the iron oxidation at this conditions, indicating that free radical scavenging rather than metal-chelating phenomenon is the basis of its antioxidant action. The fact of inhibition of lipid peroxidation by melatonin at conditions excluding iron participation also supports this hypothesis. Elucidation of the nature of common interaction among melatonin, ascorbate, and alpha-tocopherol in human placental mitochondria was the main aim of this study. In presence of 90 mum ascorbate, the inhibition of lipid peroxidation by melatonin was strong and had a feature of synergistic interaction. At presence of 30 mum ascorbate, which stimulated lipid peroxidation, melatonin caused a loss of pro-oxidant effect of ascorbate. While the interaction of melatonin with ascorbate indicated synergism, the joint action of melatonin and alpha-tocopherol was additive. When all three antioxidants were applied together, the strongest inhibition of lipid peroxidation was observed. The experimental results presented here indicated that melatonin could be considered as an effective component of antioxidant treatment of preeclampsia, allowing the use of reduced doses of vitamin C and E owing to elevated efficiency of their antioxidant activity in placenta when used in combination.

Comparison of the antioxidant system response to melatonin implant in raccoon dog (Nyctereutes procyonoides) and silver fox (Vulpes vulpes)

“…This is consistent with the opinion that melatonin influences the activity and expression of the antioxidative enzymes, i.e. glutathione peroxidase, SOD, and CAT (13,(23)(24)(25), as well as antioxidant vitamins (26).…”

Comparative evaluation of the antioxidant activity of melatonin and related indoles

“…The antioxidant properties of Mel and its ability to scavenge several radical species as part of its bioactivity have been described in the literature (Allegra et al, 2003;Reiter et al, 2003;Estevão et al, 2011), both by direct and indirect mechanisms (Barrenetxe et al, 2004;Milczarek et al, 2010). Indeed, it scavenges ROS and RNS, and metabolites formed afterwards are also radical scavengers in their turn (Tan et al, 2007).…”

Estimation of scavenging capacity of melatonin and other antioxidants: Contribution and evaluation in germinated seeds

“…In addition, melatonin reportedly scavenges singlet oxygen ( 1 O 2 ), superoxide anion radical (O 2 ÅÀ ), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO Å ) and hypochlorous acid (HClO). Several metabolites formed when melatonin interacts with radicals are also highly effective scavengers (Milczarek, Hallmann, Sokolowska, Kaletha, & Klimek, 2010). These products include cyclic 3-hydroxymelatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK).…”