Ultra low concentrations of antioxidants at experimental hypoxia of fetus – some aspects of action mechanism

The article is devoted to the analyzes the changes in phospholipids composition and activity of antioxidant enzymes in brain tissue in animals undergoing intrauterine hypoxia and treatment by ultra-low doses of antioxidants in postnatal period. Urgency of problem. Fetal hypoxia causes fetal growth retardation and cerebral ischemia in newborn. The concept of neuroprotection by antioxidants is actively used in the treatment of ischemic stroke in adults, but it is not used in infants, probably due to lack of fundamental research to prove its effectiveness. Especially there are not studied the action of ultra-low doses (ULD), despite of there was established the ability of many substances to have an effects in ultra low doses of 10 -10–10 -17M on various biological objects at the molecular level. Results. It was studied the changes of phospholipids (PL) composition and antioxidant system activity in brain tissues during the postnatal period in normal conditions and after intrauterine hypoxia. Accumulation of malondialdehyde (MDA), low activity of superoxide dismutase (SOD), decreasing the absolute amount of easily oxidized and functionally important PL (phosphatidylserine (PS) and phosphatidylinositol (PI )) in brain tissues were founded after intrauterine hypoxia at 1–5 days of life. After treatment with the water-soluble antioxidant phenazan in ULD caused decreasing of MDA concentration, that is observed at 10 day. After treatment with the fat-soluble antioxidant alpha-tocopherol decreasing of MDA level was observed at 12 day, without treatment – at 21 day. SOD and catalase activities after treatment with phenazan at ULD recovered significantly faster, then after alpha-tocopherol treatment and becomes comparable to the control, starting from 5 and 8 days of life, whereas after alpha-tocopherol introduction the SOD and catalase activity is comparable to the control only on 21 day of life. Decreasing of structural FL – phosphatidylcholine (PC), phosphatidylinositol (PEA) at 7–14 day of postnatal period after intrauterine hypoxia in brain tissues. Changes in the content of sphingomyelin (SPM) at postnatal period indicates its increasing in the first week after birth, and decreasing in the later, that’s causing an increase in rigidness of membranes and their saturation, which changes to myelination disorders in the later stages of postnatal period. Cardiolipin (CL) amount was decreased at 10 day of post hypoxic period, that creates of energy metabolism disorders in mitochondria of the brain tissues. The results demonstrate that the water-soluble antioxidant phenazan in ultralow doses is highly effective in brain tissue, as leads to early normalization of phospholipids composition and activity of antioxidant enzymes in the brain, creating favorable conditions for the development of brain function and neuroplasticity in the post hypoxic period.