The importance of “first-blood circulation stage”, a new insight into the pathogenesis of clinical manifestations of preeclampsia

Abstract

The tested hypothesis points out that exposure to environmental toxic substances originating from coal or other fossil fuels burning is the most decisive for the impacts of the metabolic synergy of nitrogen oxides as oxidants that cause hemoglobin oxidation to methemoglobin, and sulphur dioxide metabolites as inhibitors of antioxidants, in the bloodstream throughout the period of pregnancy. The main difference between the present three-stage hypothesis and other hypotheses is the assertion that, in the pathogenesis of early and late complicated pregnancy, methemoglobin takes on an important role. Methemoglobin by itself and from heme, redox-active ferric iron as a product of methemoglobin catabolism, has prooxidant properties and causes important structural and functional changes in the vascular endothelium, such as growth arrest, senescence, morphological alterations and cell apoptosis. Our own prospective study of methemoglobin in pregnancy revealed a significant rise and correlation between the ground level of SO2 and the level of methemoglobin: >1.5 g/L (r = 0.72, p < 0.01) and sulfhemoglobin (r = 0.53, p < 0.05) in the bloodstream of pregnant women which can be explained on the basis of an oxidant-antioxidant imbalance (nitrogen and sulphur synergy effects), resulting in methemoglobinemia. Methemoglobinemia and pregnancy complications like stillbirths recorded throughout the exposure period are significantly higher than those recorded in the control period (p = 0.0205), and the frequencies of reproductive loss were significantly lower in the control than in the exposure period (p < 0.05). We point out the importance of the “First-Blood circulation stage” as a new insight into the pathogenesis of the multisystemic oxidative stress and the link between a poorly perfused placenta and clinical manifestations of preeclampsia. The results suggest that the level of methemoglobin concentration in the bloodstream of pregnant women correlate with the inhalation of substances generated from coal combustion (SO2, NOx, NO, NO2 and others) and that is an early biomarker of the identification of women with a pregnancy risk, and having an significant role upon adverse effects on mother and fetus health.

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Mohorovic, L. and Micovic, V. (2012) The importance of “first-blood circulation stage”, a new insight into the pathogenesis of clinical manifestations of preeclampsia. Advances in Bioscience and Biotechnology, 3, 945-950. doi: 10.4236/abb.2012.327116.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Roberts, J.M. and Hubel, C.A. (2009) The two stege model of preeclampsia: Variations on the theme. Placenta, 30, S32-S37.
[2] Jeney, V., Balla, V., Yachie, A., Arga, Z., Vercellotti, G.M., Eaton, J.W. and Balla, G. (2002) Pro-oxidant citotoxic effects of circulatiing heme. Blood, 100, 879-887.
[3] Woollard, K.J., Sturgeon, S., Chin-Dusting, J.P., Salem, H.H. and Jackson, S.P. (2009) Erythrocyte hemolysis and hemoglobin oxidation promote ferric chloride-induced vascular injury. The Journal of Biological Chemistry, 284, 13110-13118.
[4] Mohorovic, L. (2003) The level of maternal methemoglobin during pregnancy in air polluted environment. Environmental Health Perspectives, 11, 1902-1905. doi:10.1289/ehp.6055
[5] Mohorovic, L. (2004) First two months of pregnancy-critical time for preterm delivery and low birth weight caused by the adverse effects of coal combustion toxins. Early Human Development, 80, 115-123.
[6] Poston, L., Chappell, L., Seed, P. and Shennan, A. (2011) Biomarkers of oxidative stress in preeclampsia. Pregnancy Hypertension: An International Journal of Womem’s Cardiovascular Health, 1, 22-27. doi:10.1016/j.preghy.2010.10.009
[7] Starodubtseva, M.N., Ignatenko, V.A. and Cherenkevich, S.N. (1999) Damage to erythrocytes caused by the interaction of nitriteions with hemoglobin. Biofizika, 44, 1068-1072.
[8] Kinoshita, A., Nakayama, Y., Kitayama, T., Tomita, T. and Tomita, M. (2007) Simulation study of methemoglobin reduction in erythrocytes. Differential contributions of two pathways to tolerance to oxidative stress. FEBS Journal, 274, 1449-1458.
[9] Mohorovic, L. (2007) The role of methemoglobinemia in early and late complicated pregnancy. Medical Hypotheses, 68, 1114-1119. doi:10.1016/j.mehy.2006.09.053
[10] Jaffe, E.R. (1981) Methemoglobin pathophysiology. Progress in Clinical Biological Research, 51, 133-151.
[11] Myatt, L. (2002) Role of placenta in preeclampsia. Endocrine, 19, 103-111. doi:10.1385/ENDO:19:1:103
[12] Huppertz, B. (2008) Placental origins of preeclampsia: Challenging the current hypothesis. Hypertension, 51, 970-975.
[13] Sankaralingam, S., Arenas, I.A., Lalu, M.M. and Davidge, S.T. (2006) Preeclampsia: current understanding of the molecular basis of vascular dysfunction. Expert Reviews in Molecular Medicine, 8, 1-20.
[14] Touyz, R.M. (2004) Reactive oxygen species, vascular oxidative stress, and redox signaling in hypetension: What is the clinical significance? Hypertension, 44, 248-252. doi:10.1161/01.HYP.0000138070.47616.9d
[15] Tabacova, S., Balabaeva, L. and Little, R.E. (1997) Maternal exposure to exogenous nitrogen compounds and complications of pregnancy. Archives of Environmental Health, 52, 341-7.
[16] Tabacova, S., Baird, D.D. and Balabaeva, L. (1998) Exposure to oxidazed nitrogen: lipid peroxidation and neonatal health risk. Archives of Environmental Health, 53, 214-221. doi:10.1080/00039899809605698
[17] Etlik, O., Tomur, A., Tuncer, M., Ridvanagaol, A.Y. and Andac, O. (1997) Protective effects of antioxidant vitamins on red blood cell lipoperoxidation induced by SO2 inhalation. Journal of Basic & Clinical Physiology & Pharmacology, 8, 31-43. doi:10.1515/JBCPP.1997.8.1-2.31
[18] Rust, O.A., Bofill, J.A., Zappe, D.H., Hall, J.E., Burnett, J.C. and Martin, J.N. (1997) The origin of endothelin1 in patients with severe preeclampsia. Obstetrics & Gynecology, 89, 754-757. doi:10.1016/S0029-7844(97)00093-8
[19] Schiff, E., Weiner, E., Zalel, Y., Mashiach, S., Sihai, B.M. and Shalev, E. (1994) Endothelin1, 2 levels in umbilical vein serum of intrauterine growth retarded fetuses as detected by cordocentesis. Acta Obstetricia et Gynecologica Scandinavica, 73, 21-24. doi:10.3109/00016349409013387
[20] Hjelt, K., Lund, J.T., Sherling, B., Bendixen, S., Lundstrom, K., Stovring, S., Voldsgaard, P. and Linnet, K. (1995) Methemoglobinemia among neonates in an neonatal intensive care unit. Acta Paediatrica, 84, 365-370. doi:10.1111/j.1651-2227.1995.tb13650.x

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