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2015-05-15 - Colloque/Présentation - poster - Anglais - 1 page(s)

Lenaerts Charline , Bond Liz, Tuytten Robin, Blankert Bertrand , "Marinobufagenin : extraction and LC-MS/MS identification in toad venom and human plasma as a promising preeclampsia risk stratification tool" in Bioforum 2015- ULG, Liège, Belgique, 2015

  • Codes CREF : Analyse et contrôle pharmaceutique (DI3450), Chimie analytique (DI1314), Sciences pharmaceutiques (DI3400), Métabolisme (DI3223)
  • Unités de recherche UMONS : Analyse pharmaceutique (M130)

Abstract(s) :

(Anglais) Marinobufagenin (MBG) is an endogenous bufadienolide cardiac inotrope which has a growing interest in the early diagnosis of varied volume expansion-mediated hypertensive states such as preeclampsia and end-stage renal disease hypertension. Mammalian MBG acts by inhibiting the α1 isoform of Na+,K+-ATPase, giving the compound vasoconstrictive and cardiotonic properties and resulting in hypertension and natriuresis. Elevated endogenous MBG levels have been described in pregnant mammals and especially in preeclamptic patients [1-3]. The rise of endogenous MBG appears prior the development of the main symptoms of preeclampsia (PE), leading us to consider MBG as one of the potential target in the biomarker panel for PE. Nowadays, a sensitive and accurate analytical method is needed to assess MBG in as lower level as possible in plasma. An algorithm dealing with the MBG plasma levels might be established by clinicians in the future, in order to predict, in combination with other clinical and biological markers, the risk for preeclampsia in pregnant women. A MBG standard compound is currently not commercially available. As the major source for MBG is located in the parotid glands of the Bufo Marinus toad, it forced us to develop an extraction and purification method of MBG from crystallized toad venom. The identity of the compound has been confirmed by different spectral techniques, including mass spectrometry. Currently, only marinobufagenin-like material has been found in humans using two published quantification methods based each on immunoassays [4, 5]. These techniques suffer from a lack of specificity due to cross-reactivity and tend to exhibit high variability at low concentrations [6]. This condition has led us to authenticate the presence of MBG in humans using a more specific and accessible technique, such as LC-MS/MS. The optimization of a LC-MS based assay in order to identify and quantify MBG in human plasma will be presented. A pre-extraction procedure is needed to concentrate and clean the sample prior to its analysis. The identification of MBG in non-pregnant healthy volunteers as well as in early pregnancy will be demonstrated, giving the clinicians a promising perspective for early preeclampsia risk assessment in pregnant women. References 1. Lopatin, D.A., et al., Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia. Journal of Hypertension, 1999. 17(8): p. 1179-1187. 2. Agunanne, E., et al., Marinobufagenin Levels in Preeclamptic Patients: A Preliminary Report. American Journal of Perinatology, 2011. 28(7): p. 509-514. 3. Vu, H.V., et al., Involvement of Marinobufagenin in a Rat Model of Human Preeclampsia. American Journal of Nephrology, 2005. 25(5): p. 520-528. 4. Abi-Ghanem, D., et al., A CHEMIFLUORESCENT IMMUNOASSAY FOR THE DETERMINATION OF MARINOBUFAGENIN IN BODY FLUIDS. Journal of Immunoassay and Immunochemistry, 2011. 32(1): p. 31-46. 5. Fedorova, O.V., et al., Endogenous Ligand of α1 Sodium Pump, Marinobufagenin, Is a Novel Mediator of Sodium Chloride–Dependent Hypertension. Circulation, 2002. 105(9): p. 1122-1127. 6. Jarvis, Ultra-sensitive analysis of aldosterone in serum using the AB SCIEX Triple QuadTM 6500 LC/MS/MS system, AB SCIEX, 5730212-01


Mots-clés :
  • (Anglais) LC-MS/MS
  • (Anglais) Preeclampsia
  • (Anglais) biomarker
  • (Anglais) Bufo marinus
  • (Anglais) Marinobufagenin