PRENATAL HYPERHOMOCYSTEINEMIA AND OXIDATIVE STRESS PROFILE IN THE RAT OFFSPRING

A.V. Arutjunyan (1,2), A.V. Pustygina (1), Yu.P. Milyutina (1), I.V. Zaloznyaya (2), L.S. Kozina (2)
1 -D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleyevskaya Line, 3, Saint-Petersburg, 199034, Russian Federation;
2 -Saint-Petersburg Institute of Bioregulation and Gerontology, Dinamo Pr., 3, Saint-Petersburg, 197110, Russian Federation

Introduction. Oxidative stress is developed as a result of imbalance between the generation of reactive oxygen species and activity of the antioxidant defence system. This in turn results in profound changes in metabolism of lipids, proteins and nucleic acids, which may rise in as well various diseases, as pathological states prevailing during the pregnancy course. One of the most critical obstetrical pathologies, hyperhomocysteinemia, is accompanied by generation of reactive oxygen species and is detected by an increased level of the serum-containing amino acid L-homocysteine.Hyperhomocysteinemia causes various complications in the pregnancy course that are based on uteroplacental and fetoplacental misperfusions resulting from thrombosis, vasculitis, and placental infarction. This may lead to severe developmental disorders occurring in the fetus and neonate affected by preceded prenatal hyperhomocysteinemia. Objectives. The aim of the study was to investigate the effects of prenatal hyperhomocysteinemia on profile of oxidative stress (pro- and antioxidant system indices) in the rat blood serum. Test-kits for enzyme immunoassay of nitrotyrosine, 8-hydroxy-2-dezoxyguanosine, vitamin C, and superoxide dismutase activity in blood serum were used in the present study. Results. The data obtained have shown that oxidative stress develops in rat offsprings underwent prenatal hyperhomocysteinemia. Our study of oxidative stress indices in the blood serum of the rats showed that major time-evolving destructive processes were mainly associated with the oxidative modification of proteins. This was manifested in a significant increase in nitrotyrosine content, which appeared 1-2 months after birth, being coupled with a decrease in homocysteine level. Besides, the activity of superoxide dismutase changed significantly in the blood serum of the experimental animals. Conclusion. Prenatal hyperhomocysteinemia results in the protein oxidative modification product, nitrotyrosine, being accumulated in the blood serum of the rat offspring. The data obtained implies active formation of the endothelial dysfunction marker, peroxynitrite, which may mediate main toxic effects of prenatal hyperhomocysteinemia on the offspring in the early postnatal period.
Keywords: 
hyperhomocysteinemia, pregnancy, oxidative stress, endothelium dysfunction