Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae

Федорова, О. В.; Tapilskaya, Tapilskaya N.I.; Bzhelyansky, Anton; Frolova, Elena Vladimirovna; Никитина, Е. Р.; Reznik, Vitaly A.; Kashkin, Vladimir A.; Bagrov, Alexei Y.

doi:10.1097/hjh.0b013e328333226c

Cited by 26 publications

(40 citation statements)

References 26 publications

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“…Previously, we demonstrated that in patients with preeclampsia-elevated plasma, MBG levels were associated with the inhibition of erythrocyte Na/K-ATPase which was reversible by both 3E9 mAb and Digibind [14] and that in preeclamptic placentae, bufadienolide CTS, including MBG, rather than EO, represents a target for Digibind [27]. In the present study, both 3E9 mAb and Digibind ex vivo restored activity of Na/K-ATPase in erythrocytes from patients with CKD.…”

Section: Discussionsupporting

confidence: 67%

Endogenous cardiotonic steroids in chronic renal failure

Колмакова¹,

Haller

Kennedy

et al. 2011

Nephrology Dialysis Transplantation

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Background. Previous reports demonstrated that digitalislike cardiotonic steroids (CTS) contribute to the pathogenesis of end-stage renal disease. The goal of the present study was to define the nature of CTS in patients with chronic kidney disease (CKD) and in partially nephrectomized (PNx) rats. Methods. In patients with CKD and in healthy controls, we determined plasma levels of marinobufagenin (MBG) and endogenous ouabain (EO) and erythrocyte Na/K-ATPase activity in the absence and in the presence of 3E9 anti-MBG monoclonal antibody (mAb) and Digibind. Levels of MBG and EO were also determined in sham-operated Sprague-Dawley rats and in rats following 4 weeks of PNx. Results. In 25 patients with CKD plasma, MBG but not EO was increased (0.86 6 0.07 versus 0.28 6 0.02 nmol/L, P < 0.01) and erythrocyte Na/K-ATPase was inhibited (1.24 6 0.10 versus 2.80 6 0.09 lmol Pi/mL/h, P < 0.01) as compared to that in 19 healthy subjects. Ex vivo, 3E9 mAb restored Na/K-ATPase in erythrocytes from patients with CKD but did not affect Na/K-ATPase from control subjects. Following chromatographic fractionation of uremic versus normal plasma, a competitive immunoassay based on anti-MBG mAb detected a 3-fold increase in the level of endogenous material having retention time similar to that seen with MBG. A similar pattern of CTS changes was observed in uremic rats. As compared to sham-operated animals, PNx rats exhibited 3-fold elevated levels of MBG but not that of EO. Conclusions. In chronic renal failure, elevated levels of a bufadienolide CTS, MBG, contribute to Na/K-ATPase inhibition and may represent a potential target for therapy.

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Section: Discussionsupporting

confidence: 67%

Endogenous cardiotonic steroids in chronic renal failure

Колмакова¹,

Haller

Kennedy

et al. 2011

Nephrology Dialysis Transplantation

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“…MBG has been identified in the placenta, and its increase in preeclampsia have been well documented (22). In our study in offspring of dams on HS or LS, the expression of ␣ 1 -Na ϩ -K ϩ -ATPase in fetal kidneys at term was decreased in parallel with the elevation of MBG resembling the decrease of plasmalemmal ␣ 1 -Na ϩ -K ϩ -ATPase observed in response to MBG in vitro (41).…”

Section: F351supporting

confidence: 65%

Both high and low maternal salt intake in pregnancy alter kidney development in the offspring

Koleganova¹,

Piecha

Ritz

et al. 2011

American Journal of Physiology-Renal Physiology

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In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.

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“…Previous research by ourselves 27 and others [28][29][30][31][32] had indicated that an SP inhibitor or EDLF exists in placental homogenates, with higher amounts observed in placenta from women having PE. Our initial hypothesis in this study was that the placenta produces such an EDLF.…”

Section: Resultsmentioning

confidence: 99%

Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

Esplin

Adair

et al. 2012

Reprod. Sci.

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Endogenous digitalis-like factors (EDLFs) appear to be hypertensiogenic and increased in the serum and placenta of women with preeclampsia (PE), a complication of pregnancy. Digibind, an anti-digoxin antibody Fab fragment, reverses in vitro effects of EDLF and in vivo features of PE. We used Digibind in a radioimmunoassay to measure EDLF and compared this to a bio-functional assay of EDLF with good agreement. These methods confirmed that human placenta was a source of EDLF, synthesizing and releasing EDLF into the media of cultured human placental tissue. Ketoconazole, a steroid synthesis inhibitor, and 17-OH progesterone, a possible substrate of steroid synthesis, were shown to inhibit or increase EDLF release respectively, suggesting overlap of synthetic pathways. Abnormalities of PE such as placental hypoxia, increased reactive oxygen species and increased pro-inflammatory cytokines were demonstrated to increase placental EDLF release. These findings strongly support placental production of EDLF with increased release due to features of PE.

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Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae

Cited by 26 publications

References 26 publications

Endogenous cardiotonic steroids in chronic renal failure

Endogenous cardiotonic steroids in chronic renal failure

Both high and low maternal salt intake in pregnancy alter kidney development in the offspring

Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

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