Digoxin immune Fab protects endothelial cells from ouabain‐induced barrier injury. Research output: Contribution to journal › Article. Am J Reprod Immunol 2012; 67: 66–72. ), digitoxin: 59 % Marzo et al. Digoxin and ouabain reduced the influx and had no appreciable effect on the efflux ofpotassium, so that the auricles lost potassium. Compared to digoxin, ouabain is more hydrophilic and cannot easily cross the Brain–Blood Barrier (BBB) (Sugimoto et al., 2011). (A) Structural representation of the CTSs digoxin, bufalin, and ouabain. Remarkably, these effects are independent of the inhibition of the Na/K pump. Digoxin, which is synthesized in adrenal glands, seems to counteract the hypertensinogenic action of ouabain in rats, as do antibodies against ouabain, for example, (Digibind) and rostafuroxin (PST 2238), a selective ouabain antagonist. Digoxin and digitoxin are widely used in the treatment of heart diseases. Moreover, digoxin was shown to induce changes in intracellular membrane traffic in neuronal cells, whereas ouabain does not possess this ability and even antagonized digoxin effect. Activation of c-SRC underlies the differential effects of ouabain and digoxin on Ca2+ signaling in arterial smooth muscle cells Only ouabain in small doses stimulates the sodium pump; digoxin does not show this effect. In this study, we examined renal tubular cell handling of digoxin and ouabain using LLC-PK1 cells, a model of proximal renal tubular cells. Digoxin and ouabain are steroid drugs that inhibit the Na+/K+-ATPase, and are widely used in the treatment of heart diseases. Digoxin: The excretion of Ouabain can be decreased when combined with Digoxin. Acetyldigitoxin: Used for fast digitalization in congestive heart failure. Plasma ouabain, BP, and all evoked responses were normal one week following interruption of the ouabain infusion. The K +and Mg2 ions are represented by purple and yellow spheres, respectively. Digoxin for 24 h and 48 h of incubation in MDA-MB-231 cells proved to be only slightly more potent than ouabain, with IC50 values of 122 ± 2 and 70 ± 2 nM, respectively, compared to 150 ± 2 and 90 ± 2 nM for ouabain. Ouabain and digoxin activate the cellular proteasome, instigating ER degradation, which causes the inhibition of 17 -estradiol signaling, induces the cell cycle blockade in the G2 phase, and triggers apoptosis. Digoxin, ouabain, zaragozic acid and the BCA (bicinchoninic acid) kit for protein measurement were from Sigma. Virus titers of single dose treatment of ouabain and digoxin showed a >99% inhibition of SARS-CoV-2 replication. were of the order of 10 −6 for ouabain and somewhat higher for digoxin. Indeed, H9c2 cells treated with digoxin and ouabain had low levels of intracellular cholesterol and showed a time-dependent cholesterol accumulation in the culture medium. In an in vitro assay for the inhibitory effects on Na ϩ ,K ϩ -ATPase activity, 20 ng of ouabain caused 29% inhibition, but 20 ng of ouabain plus 13 or 53 ng of digoxin caused only 16% or 4% inhibition, respectively. Ouabain has become the standard tool to investigate the mode of action of cardiotonic steroids, and results with ouabain are regarded as generally valid for all cardiac glycosides. Digoxin and ouabain reduced the influx and had no appreciable effect on the efflux of potassium, so that the auricles lost potassium. Abstract—Digoxin prevents ouabain-induced hypertension in rats. Irregularities or failure of contraction occurred when the tissue potassium was reduced by about 15%. alpha 1-isoform expression decreased in the ouabain group and was unchanged in the digoxin group. 10 Scopus citations. Ouabain and digoxin enhanced the histamine release while digitoxigenin either had no effect or was slightly inhibitory. Digoxin: A cardiac glycoside used in the treatment of mild to moderate heart failure and for ventricular response rate control in chronic atrial fibrillation. It lowers BP in ouabain- and adducin-dependent hypertension in rats and is a promising new class of antihypertensive medication in humans. Poisoning the hearts of dogs and of dog heart-lung preparations with ouabain or digoxin to the extent of producing ventricular tachycardia or ventricular fibrillation caused a severe depletion of the phosphocreatine stores of the tissue. DLSTRISUTION OF OUABAIN AND DIGOXIN IN THE RAT AND GUINEA PIG S. Dutta and B. H. Marks Department of Pharmacology, Ohio State University College of Medicine, Columbus, Ohio (Received 14 February 1966; is final form 21 1larch 1966) THE pattern of distribution of various digitaloids has been studied by a number of investigators ( 1, 2, 3) . Our results suggest that weight loss during opiate withdrawal is mediated … Such occurrence, however, has never been described in patients treated with digoxin. In comparison with chloroquine, ouabain and digoxin were much more e"ective. Comparative Cardiotoxicity of Low Doses of Digoxin, Ouabain, and Oleandrin. The threshold concentrations which produced effects within 20 min. The cells were used in suspension for binding experiments and in monolayers on permeable filters for transport studies. 2020 Jun 01;: Authors: Botelho AFM, Miranda ALS, Freitas TG, Milani PF, Barreto T, Cruz JS, Melo MM Abstract The aim of this study was to evaluate the comparative effects of CGs on heart physiology. Both ouabain and digoxin stimulated expression of the alpha 3-isoform, whereas alpha 2 was unchanged in those two groups. Thethreshold concentrations whichproduced effects within 20 min. As digoxin and ouabain increase the synthesis of cholesterol, one might expect that these cells ‘fill up’ with cholesterol. Cardiac glycosides are promising anticancer drugs. Therefore, the pharmacological action of ouabain is more peripheral, which explains why it has no effect on locomotion in mice. Ouabain and digoxin activate the cellular proteasome, instigating ERα degradation, which causes the inhibition of 17β-estradiol signaling, induces the cell cycle blockade in the G2 phase, and triggers apoptosis. Deslanoside: For the treatment and management of Congestive cardiac insufficiency, arrhythmias and heart failure. Comparison of the effects of aminosugar cardiac glycosides wth ouabain and digoxin on Na+, K+ adenosine triphosphatase and cardiac contractile force. Digoxin and Fab fragments had no effects on either function. In the presence of lithium or lanthanum the enhancement of the histamine release was counteracted. December 2020; Cardiovascular Toxicology 20(1) DOI: 10.1007/s12012-020-09579-1. When not otherwise specified, all of the other reagents were purchased from Sigma. The exact mechanism of action of these drugs has remained an enigma. 1. rat: ouabain: 24 % digoxin: 75 % digitoxin: 86 %, guinea pig: ouabain: 48 %, digoxin: 20 % (! Comparative Cardiotoxicity of Low Doses of Digoxin, Ouabain, and Oleandrin. This work was aimed at determining the cardioprotective effect of digitalis glycosides in rat heart, and to relate it with Na+, K+-ATPase inhibition and ERK1/2 activation. Problem Endogenous digitalis‐like factors (EDLF) inhibit sodium pump Na + /K + ATPase activity, and maternal EDLF levels are elevated in preeclampsia (PE). Milrinone does not affect locomotion in mice either. There are marked differences between the effects of digoxin and ouabain. In a second study, BP increased in ouabain (15 μg/kg/day, n=23), but not digoxin (30 μg/kg/day, n=12), or vehicle-infused (n=16) rats. activity of ouabain and digoxin against SARS-CoV-2 infection [8]. Digoxin is known to be secreted by renal tubular cells, but the mechanisms are still not fully understood. The ATP levels were slightly lowered or remained unchanged. A heterogeneous immunoassay for digoxin having improved sensitivity and precision is disclosed. 2. To examine acute ouabain–digoxin interactions, we tested these and related CTSs on myogenic tone (MT) in pressurized rat mesenteric small arteries and glutamate‐evoked Ca 2+ transients in primary cultured rat hippocampal neurones. were ofthe order of 10-6 for ouabain and somewhat higher for digoxin. Overview; Fingerprint; Abstract . Remarkably, these e ects are independent of the inhibition of the Na/K pump. Nevertheless, prolonged ouabain, but not digoxin, administration induces hypertension; moreover, digoxin antagonizes the hypertensinogenic effect of ouabain. They may also have additional effects, such as on metabolism of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on the synthesis of cholesterol. Plasma and kidney levels of ouabain immunoreactivity were increased 4-8 fold in ouabain infused rats while blood pressure and plasma levels of ouabain returned to normal one week following discontinuation of the steroid infusion. Dihydrostreptomycin: The risk or severity of adverse effects can be increased when Dihydrostreptomycin is combined with Ouabain. Robert William Caldwell, C. B. Nash. The improvement results from the use of ouabain rather than digoxin as the means for separating the bound and free labeled components. We have recently shown that the cardiac glycosides digitoxin, digoxin and ouabain induce selective killing of lung cancer cells, and that the cytotoxicity of digitoxin against these cells occurs at concentrations below those observed in the plasma of cardiac patients treated with this drug (Oncogene, 2013. doi: 10.1038/onc.2013.229). Cardiovasc Toxicol. In the presence of calcium, the glycosides only affected potassium uptake and histamine release slightly. !e half-maximal inhibitory concentration (IC50) of ouabain and digoxin were determined at a nanomolar concentration. bufalin, digoxin, and ouabain (5) is depicted in blue, green, and gray cartoons, respectively, and the bufalin, digoxin, and ouabain molecules are represented by magenta, orange, and dark gray sticks, respectively. Dihydrotachysterol: The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Dihydrotachysterol is combined with Ouabain. 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