Am J Perinatol 2011; 28(7): 509-514
DOI: 10.1055/s-0031-1272965
© Thieme Medical Publishers

Marinobufagenin Levels in Preeclamptic Patients: A Preliminary Report

Enoch Agunanne1 , Darijana Horvat1 , Recherael Harrison1 , M. Nasir Uddin1 , Richard Jones2 , Thomas J. Kuehl2 , Daad Abi Ghanem3 , Luc R. Berghman3 , Xinzhong Lai4 , Jing Li4 , 5 , Daniel Romo4 , 5 , Jules B. Puschett1
  • 1The Nephrology/Hypertension Division, Department of Medicine, Texas A&M Health Science Center/Scott & White, Temple
  • 2The Department of Obstetrics and Gynecology, Texas A&M Health Science Center/Scott & White, Temple
  • 3The Department of Poultry Science, Texas A&M University, College Station, Texas
  • 4The Department of Chemistry, Texas A&M University, College Station, Texas
  • 5The Natural Products LINCHPIN Laboratory, Texas A&M University, College Station, Texas
Further Information

Publication History

Publication Date:
04 March 2011 (online)

ABSTRACT

Preeclampsia is a disorder resulting in significant fetomaternal complications with no definitive pharmacological intervention. A bufadienolide, marinobufagenin, has been implicated in the etiology of preeclampsia. We investigated both the blood and urine levels of marinobufagenin in preeclamptic and control subjects. Preeclamptic and normotensive pregnant women were recruited at various gestational age periods. Blood and urine specimens were obtained and analyzed for marinobufagenin levels and creatinine. The former determination was performed utilizing a new, novel chemifluorescent enzyme-linked immunosorbent assay. The marinobufagenin levels were higher in preeclamptics than in the controls in both serum and urine at various gestational age periods. Additionally, the mean level of marinobufagenin in the preeclamptic group was significantly greater than in controls in both blood and urine specimens (p < 0.05). These data are consistent with a role for marinobufagenin in the etiology of preeclampsia. This study demonstrated comparable results in blood and urine samples. This suggests that subsequent studies on levels of marinobufagenin as a screening test for preeclampsia could be done utilizing urine samples, which are easier to obtain, less invasive, more cost-effective, and as accurate as the serological tests.

REFERENCES

  • 1 Pridjian G, Puschett J B. Preeclampsia. Part 1: clinical and pathophysiologic considerations.  Obstet Gynecol Surv. 2002;  57 598-618
  • 2 Pridjian G, Puschett J B. Preeclampsia. Part 2: experimental and genetic considerations.  Obstet Gynecol Surv. 2002;  57 619-640
  • 3 Ness R B, Roberts J M. Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications.  Am J Obstet Gynecol. 1996;  175 1365-1370
  • 4 Puschett J B, Agunanne E, Uddin M N. Marinobufagenin, resibufogenin and preeclampsia. Biochim Biophys Acta.  2010;  2 1246-1253
  • 5 Maynard S E, Min J Y, Merchan J et al.. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.  J Clin Invest. 2003;  111 649-658
  • 6 Hypertensive disorders in pregnancy. Chapter 34. In:, Cunningham F G, Gant N F, Leveno K G, Gilstrap L C, Hauth J C, Wenstrom K D, eds. Williams Textbook of Obstetrics, 22nd ed. New York: McGraw-Hill; 2005: 762-808
  • 7 Vu H V, Ianosi-Irimie M R, Pridjian C A et al.. Involvement of marinobufagenin in a rat model of human preeclampsia.  Am J Nephrol. 2005;  25 520-528
  • 8 Abi-Ghanem D, Berghman L R, Romo D et al.. A chemifluorescent immunoassay for the determination of marinobufagenin in body fluids.  J Immunoassay Immunochem. 2011;  32 31-46
  • 9 Averina I V, Tapilskaya N I, Reznik V A et al.. Endogenous Na/K-ATPase inhibitors in patients with preeclampsia.  Cell Mol Biol (Noisy-le-grand). 2006;  52 19-23
  • 10 Lopatin D A, Ailamazian E K, Dmitrieva R I et al.. Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia.  J Hypertens. 1999;  17 1179-1187
  • 11 Gonick H C, Ding Y, Vaziri N D, Bagrov A Y, Fedorova O V. Simultaneous measurement of marinobufagenin, ouabain, and hypertension-associated protein in various disease states.  Clin Exp Hypertens. 1998;  20 617-627
  • 12 Bagrov A Y, Fedorova O V, Dmitrieva R I, French A W, Anderson D E. Plasma marinobufagenin-like and ouabain-like immunoreactivity during saline volume expansion in anesthetized dogs.  Cardiovasc Res. 1996;  31 296-305
  • 13 Bagrov A Y, Fedorova O V, Austin-Lane J L, Dmitrieva R I, Anderson D E. Endogenous marinobufagenin-like immunoreactive factor and Na+, K+ATPase inhibition during voluntary hypoventilation.  Hypertension. 1995;  26 781-788
  • 14 Songu-Mize E, Bealer S L, Caldwell R W. Effect of DOCA-salt treatment duration and anteroventral third ventricle lesions on a plasma-borne sodium pump inhibitor in rats.  J Hypertens. 1987;  5 461-467
  • 15 Deray G, Pernollet M G, Devynck M A et al.. Plasma digitalislike activity in essential hypertension or end-stage renal disease.  Hypertension. 1986;  8 632-638
  • 16 Sagnella G A, Jones J C, Shore A C, Markandu N D, MacGregor G A. Evidence for increased levels of a circulating ouabainlike factor in essential hypertension.  Hypertension. 1986;  8 433-437
  • 17 Whitley G S, Cartwright J E. Trophoblast-mediated spiral artery remodelling: a role for apoptosis.  J Anat. 2009;  215 21-26
  • 18 LaMarca H L, Morris C A, Pettit G R, Nagowa T, Puschett J B. Marinobufagenin impairs first trimester cytotrophoblast differentiation.  Placenta. 2006;  27 984-988
  • 19 Uddin M N, Horvat D, Glaser S S et al.. Marinobufagenin inhibits proliferation and migration of cytotrophoblast and CHO cells.  Placenta. 2008;  29 266-273
  • 20 Norwitz E R, Schust D J, Fisher S J. Implantation and the survival of early pregnancy.  N Engl J Med. 2001;  345 1400-1408
  • 21 Pijnenborg R, Dixon G, Robertson W B, Brosens I. Trophoblastic invasion of human decidua from 8 to 18 weeks of pregnancy.  Placenta. 1980;  1 3-19
  • 22 Vu H, Ianosi-Irimie M, Danchuk S et al.. Resibufogenin corrects hypertension in a rat model of human preeclampsia.  Exp Biol Med (Maywood). 2006;  231 215-220
  • 23 Agunanne E, Horvat D, Uddin M N, Puschett J B. The treatment of preeclampsia in a rat model employing Digibind.  Am J Perinatol. 2010;  27 299-305
  • 24 Horvat D, Severson J, Uddin M N, Mitchell B, Puschett J B. Resibufogenin prevents the manifestations of preeclampsia in an animal model of the syndrome.  Hypertens Pregnancy. 2010;  29 (1) 1-9

Jules B PuschettM.D. 

Professor of Medicine, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center/Scott & White

2401 S. 31st Street, Medical Education Center, 407 L, Temple, TX 76508

Email: jpuschett@swmail.sw.org

    >