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


Address reprint requests to Ryszard Milczarek, Department of Pharmaceutical Biochemistry, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.


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 α-tocopherol in human placental mitochondria was the main aim of this study. In presence of 90 μm ascorbate, the inhibition of lipid peroxidation by melatonin was strong and had a feature of synergistic interaction. At presence of 30 μm 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 α-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.