Udział reaktywnych form tlenu w utlenianiu i redukcji żelaza w mikrosomach łożyska ludzkiego i nowy potencjalny mechanizm działania dysmutazy ponadtlenkowej i peroksydazy glutationowej

Ryszard Milczarek, Joanna Ruda, Krystian Kaletha, Jerzy Klimek

Ann. Acad. Med. Gedan. 2009 (vol. 39), No 1:
Publication date: 2009-02-01
Language: pl


Free radicals and reactive oxygen species (ROS) play an important role in the physiology of pregnant women but they can cause some disease states when overproduced. We revealed that endoplasmic reticulum of syncytiotrophoblast may be an important source of lipid peroxides in pregnancy. During NADPH-dependent lipid peroxidation, placental microsomes produce a significant amount of TBARS. Interconversion of Fe(II)↔Fe(III) and Fe(II)/Fe(III) ratio play the key role in the mechanism of NADPH-dependent lipid peroxidation. Thus the goal of this study was to examine the participation of ROS in Fe(II)↔Fe(III) interconversion. Presence of NADPH-generating system (NADPH-GS) with Fe(II) or Fe(III) cause together a strong rise in TBARS synthesis in human placental microsomes. When Fe(III) was added to the incubation medium TBARS production was linear during the incubation. If Fe(II) was added to the same medium a lag phase lasting several minutes in TBARS production was observed. It can be explained by the necessity of obtaining a proper Fe(III)/Fe(II) ratio. Thus we measured iron oxidation in the presence of microsomes and NADPH-GS. Fe(II) was oxidized quickly during incubation in the applied conditions. Superoxide dismutase significantly inhibited Fe(II) oxidation. On the other hand catalase strongly accelerated Fe(II) oxidation. The effect of cumene hydroperoxide – an analog of lipid hydroperoxides (which is an excellent substrate for glutathione peroxidase) on Fe(II) oxidation was determined, as well. Cumene hydroperoxide strongly accelerates Fe(II) oxidation. The obtained results allow us to conclude that during NADPH-dependent lipid peroxidation in human placental microsomes reactive oxygen species (like superoxide radical, lipid hydroperoxide) can accelerate Fe(II) oxidation and increase Fe(III)/Fe(II) ratio. Thus, antioxidant enzymes such as superoxide dismutase and glutathione peroxidase prevent Fe(II) oxidation and in this way they can inhibit lipid peroxidation.