Exploration of the Underlying Nutritional, Inflammatory and Oxidative Stress Pathological Mechanisms in Preeclampsia using Principal Component Analysis

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  •   Charles Bitamazire Businge

  •   Benjamin Longo-Mbenza

  •   Andre Pascal Kengne

Abstract

Normal pregnancy is characterized by a mild systemic inflammatory response and progressive increase in serum inflammatory cytokines that peak in the third trimester. During pregnancy pre-existing inflammatory conditions, acquired oxidative stress arising from the placenta malfunction and nutritional deficiencies can trigger intense systemic responses that lead to endothelial activation, dysfunction and preeclampsia. We investigated the principal nutritional, oxidative and inflammatory pathways that trigger the clinical manifestation of preeclampsia.


This case-control study included 250 women with preeclampsia and 150 normotensive pregnant women. Urinary Iodine concentration (IUC) and serum levels of Ferritin, Thyroid-stimulating Hormone (TSH), selenium, Nitric Oxide (NO) gamma glutamyl transferase (GGT), Rheumatoid factor, and high sense C-reactive protein (hs-CRP) of cases and controls were compared using the student’s t and the Mann-Whitney U tests. Principal component analysis was carried out to delineate the patterns of association between nutritional, inflammatory and oxidative markers and preeclampsia.


The main pathophysiological pathways identified were the interactions between selenium/iodine deficiency and elevated serum TSH (endothelial dysfunction); serum ferritin, GGT, CRP and low urinary iodine concentration (inflammatory oxidative stress); elevated serum hs-CRP and Rheumatoid factor subclinical inflammation and immune cell activation) and high T3/T4 ratio (acute TSH stimulation of thyroid with low thyroid iodine stores)


Combined selenium and iodine deficiency resulting into elevated TSH, low NO and preferential T3 secretion; acute inflammatory conditions associated with elevated serum GGT, CRP, and Ferritin; and subclinical inflammatory conditions characterized by autoimmunity are some of the major oxidant and inflammatory pathways associated with increased risk of preeclampsia.


Keywords: inflammation, iodine, preeclampsia, oxidative stress, selenium, thyroid-dysfunction

References

C.W. Redman and I.L. Sargent. Preeclampsia and the systemic inflammatory response. Semin Nephrol, vol 24, no. 6, pp. 565-70. 2004.

G.P. Sacks, K. Studena, K. Sargent and C.W. Redman. Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am J Obstet Gynecol, vol. 179, no. 1, pp. 80-6. 1998.

C.W. Redman, G.P. Sacks and I.L. Sargent. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol, vol. 180, no. 2 Pt 1, pp. 499-506. 1999.

A.L. Tranquilli, G. Dekker, L. Magee, J. Roberts, B.M. Sibai, W. Steyn, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens, vol. 4, no. 2, pp. 97-104. 2014.

T.G. Pickering, J.E. Hall, L.J. Appel, B.E. Falkner, J.W. Graves, M.N. Hill MN, et al. Recommendations for blood pressure measurement in humans: an AHA scientific statement from the Council on High Blood Pressure Research Professional and Public Education Subcommittee. J Clin Hypertens (Greenwich), vol. 7, no. 2, pp. 102-109. 2005.

D.B. Ngo, L. Dikassa, W. Okitolonda, T.D. Kashala, C. Gervy, J. Dumont, et al. Selenium status in pregnant women of a rural population (Zaire) in relationship to iodine deficiency. Trop Med Int Health, vol. 2, no. 6, pp. 572-81, 1997.

D. Glinoer. The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab, vol. 18, no. 2, pp. 133-52. 2004

M. Zimmermann. The Effects of Iodine Deficiency in Pregnancy and Infancy. Paediatric and perinatal epidemiology, vol. 26, Suppl 1, pp. 108-17. 2012.

P.P. Smyth. Role of iodine in antioxidant defence in thyroid and breast disease. Biofactors, vol. 19, no. 3-4, pp. 121-130. 2003.

10. Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005;4:5.

L. Tian, L. Zhang, J. Liu, T. Guo, C. Gao and J. Ni. Effects of TSH on the function of human umbilical vein endothelial cells. J Mol Endocrinol, vol 52, no. 2, pp. 215-222. 2014.

A. Dardano, L. Ghiadoni, Y. Plantinga, N. Caraccio, A. Bemi, E. Duranti, et al. Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma. J Clin Endocrinol Metab, vol. 91, no. 10, pp. 4175-8. 2006.

E. Lioudaki, N.G. Mavroeidi, D.P. Mikhailidis, E.S. Ganotakis. Subclinical hypothyroidism and vascular risk: an update. Hormones (Athens), vol. 12, no. 4, pp. 495-506. 2013.

D.H. O'Leary and J.F. Polak JF. Intima-media thickness: a tool for atherosclerosis imaging and event prediction. Am J Cardiol, vol. 90, no. 10c, pp. 18l-21l. 2002.

E. Lapice, S. Maione, L. Patti, P. Cipriano, A.A. Rivellese, G. Riccardi G, et al. Abdominal adiposity is associated with elevated C-reactive protein independent of BMI in healthy nonobese people. Diabetes Care, vol. 32, no. 9, pp. 1734-6. 2009.

R. Anty, S. Bekri, N. Luciani, M.C. Saint-Paul, M. Dahman, A. Iannelli, et al. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH. Am J Gastroenterol, vol. 101, no. 8, pp.1824-33. 2006.

WHO. C-reactive protein concentrations as a marker of inflammation or infection for interpreting biomarkers of micronutrient status. Geneva: World Health Organization; 2014.

M.C. Dao, S. Sen, C. Iyer, D. Klebenov and S.N. Meydani. Obesity during pregnancy and fetal iron status: is Hepcidin the link? J Perinatol, vol. 33, no. 3, pp. 177-81. 2013.

V. Manolov, B. Marinov, M. Velizarova, B. Atanasova, V. Vasilev, K. Tzatchev, et al. Anemia in pregnancy and serum hepcidin levels. Int J adv Res, vol 3, no.1, pp.758-61. 2015.

G. Toldi, B. Stenczer, A. Molvarec, Z. Takáts, G. Beko, J. Rigó Jr., et al. Hepcidin concentrations and iron homeostasis in preeclampsia. Clin Chem Lab Med, vol.48, no. 10, pp. 1423-6. 2010.

R. Drozdz, C. Parmentier, H. Hachad, P. Leroy, G. Siest and M. Wellman. gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med, vol 25, no. 7, pp. 786-92, 1998.

M. Enoiu, H. Aberkane, J.F. Salazar, P. Leroy, J. Groffen, G. Siest, et al. Evidence for the pro-oxidant effect of gamma-glutamyltranspeptidase-related enzyme. Free Radic Biol Med, vol. 29, no. 9, pp. 825-33, 2000.

R. Winkler, S. Griebenow and W. Wonisch. Effect of iodide on total antioxidant status of human serum. Cell Biochem Funct, vol. 18, no. 2, pp. 143-6. 2000.

M. Gulaboglu, B. Borekci and I. Delibas I. Urine iodine levels in preeclamptic and normal pregnant women. Biol Trace Elem Res, vol. 136, no. 3, pp. 249-57. 2010.

C.Y. Chen, C.P. Chen and K.H. Lin. Biological functions of thyroid hormone in placenta. Int J Mol Sci, vol. 16, no. 2, pp. 4161-79. 2015.

C.W. Redman and I.L. Sargent. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000;21(7):597-602. 2000.

A. De Vivo, G. Baviera, D. Giordano, G. Todarello, F. Corrado and R. Deanna. PlGF and sFlt-1 as markers for predicting pre-eclampsia. Acta Obstet Gynecol Scand, vol. 87, no. 8, pp. 837-42. 2008.

R. Burns, F. Azizi, M. Hedayati, P. Mirmiran, C. O'Herlihy and P.P. Smyth. Is placental iodine content related to dietary iodine intake? Clin Endocrinol (Oxf), vol. 75, no. 2, pp. 261-4. 2011.

S. Venkatesha, M. Toporsian, C. Lam, J. Hanai J, T. Mammoto, Y.M. Kim, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med, vol.12, no. 6, pp. 642-9. 2006.

T.A. Pearson, G.A. Mensah, Y. Hong and S.C. Smith. CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease. Circulation, Vol. 110, no. 25, pp. e543-e4. 2004.

M. Shipley, A. Rahman, D. O’Gradaigh and R. Conway. “Rheumatology and bone disease”. In Kumar and Clark’s Clinical Medicine. 7th edn. P. Kumar and M. Clark eds. London Elsevier Saunders, 2012, ch 11, pp. 493–560.

D. Glinoer. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev, vol. 18, no. 3, pp. 404-33.1997.

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How to Cite
Businge, C. B., Longo-Mbenza, B., & Kengne, A. P. (2021). Exploration of the Underlying Nutritional, Inflammatory and Oxidative Stress Pathological Mechanisms in Preeclampsia using Principal Component Analysis. European Journal of Medical and Health Sciences, 3(4), 19-24. https://doi.org/10.24018/ejmed.2021.3.4.932