On the Differences Between Ouabain and Digitalis Glycosides

Fuerstenwerth, Hauke

doi:10.1097/mjt.0b013e318217a609

Cited by 40 publications

(36 citation statements)

References 56 publications

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“…In addition, at low concentrations binding of ouabain to NKA activates multiple signal transduction pathways [95, 96]. Recent research has confirmed the uniqueness of ouabain; supported by the fact that ouabain has a different mechanism of action to digitalis glycosides [97]. Experiments with extremely low concentrations (10 -8 M) of ouabain in isolated working rat hearts provide strong evidence that the cardioprotective effect of ouabain may be mediated by activation of transduction pathways rather than by inhibition of NKA [98].…”

Section: Ouabain Is Different From Digitalis Glycosidesmentioning

confidence: 99%

“…Ouabain exerts its therapeutic effects already in low nanomolar and even picomolar concentrations. In addition, a critical analysis of the available data proposes that Strophanthus glycosides have a distinct different mode of action than Digitalis glycosides [97]. Digitalis glycosides mimic the effects of catecholamines, whereas Strophanthus glycosides counteract sympathetic activity.…”

Section: Ouabain Is Oats For the Starving Myocardiummentioning

confidence: 99%

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Rethinking Heart Failure

Fürstenwerth¹

2012

Cardiol Res

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An increasing body of clinical observations and experimental evidence suggests that cardiac dysfunction results from autonomic dysregulation of the contractile output of the heart. Excessive activation of the sympathetic nervous system and a decrease in parasympathetic tone are associated with increased mortality. Elevated levels of circulating catecholamines closely correlate with the severity and poor prognosis in heart failure. Sympathetic over-stimulation causes increased levels of catecholamines, which induce excessive aerobic metabolism leading to excessive cardiac oxygen consumption. Resulting impaired mitochondrial function causes acidosis, which results in reduction in blood flow by impairment of contractility. To the extent that the excessive aerobic metabolism resulting from adrenergic stimulation comes to a halt the energy deficit has to be compensated for by anaerobic metabolism. Glucose and glycogen become the essential nutrients. Beta-adrenergic blockade is used successfully to decrease hyperadrenergic drive. Neurohumoral antagonists block adrenergic over-stimulation but do not provide the heart with fuel for compensatory anaerobic metabolism. The endogenous hormone ouabain reduces catecholamine levels in healthy volunteers, promotes the secretion of insulin, induces release of acetylcholine from synaptosomes and potentiates the stimulation of glucose metabolism by insulin and acetylcholine. Ouabain stimulates glycogen synthesis and increases lactate utilisation by the myocardium. Decades of clinical experience with ouabain confirm the cardioprotective effects of this endogenous hormone. The so far neglected sympatholytic and vagotonic effects of ouabain on myocardial metabolism clearly make a clinical re-evaluation of this endogenous hormone necessary. Clinical studies with ouabain that correspond to current standards are warranted.

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Section: Ouabain Is Different From Digitalis Glycosidesmentioning

confidence: 99%

Section: Ouabain Is Oats For the Starving Myocardiummentioning

confidence: 99%

Rethinking Heart Failure

Fürstenwerth¹

2012

Cardiol Res

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“…The eighteen candidates in this report were selected from sixty credible leads by a scientific panel; they covered a range of potentially promising mechanisms of action against EBOV. Brief details of the compounds nominated for inclusion are outlined below: Ouabain: Originally used for the treatment of heart diseases [5], which has been demonstrated to reduce EBOV replication by around half when testing in vitro in a study looking into the viral protein 24 (VP24) protein and the interruption of cellular interacting proteins [6]17-DMAG: An inhibitor of heat shock protein 90 (HSP90), which has been shown to reduce in vitro EBOV replication [7]BGB324: An inhibitor of Axl receptor tyrosine kinase, which appears to be involved with Ebola virus entry into host cells [8]JB1a: An antibody therapy, targeting beta-1 integrins, which have been proposed to facilitate the entry of filoviruses; treatment of target cells with the JB1a clone reduced infection using a vesicular stomatitis virus (VSIV) pseudotyped with EBOV glycoprotein [9]Omeprazole and esomeprazole magnesium: Members of the benzimidazoles that may stop viral entry via clathrin-mediated endocytosis by raising the endosomal pH. Both compounds were shown to inhibit lentivirus-based pseudotypes expressing EBOV glycoprotein [10]…”

Section: Introductionmentioning

confidence: 99%

“…Ouabain: Originally used for the treatment of heart diseases [5], which has been demonstrated to reduce EBOV replication by around half when testing in vitro in a study looking into the viral protein 24 (VP24) protein and the interruption of cellular interacting proteins [6]…”

Section: Introductionmentioning

confidence: 99%

Antiviral Screening of Multiple Compounds against Ebola Virus

Dowall

Bewley

Watson

et al. 2016

Viruses

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In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

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“…Despite the structural similarities between digoxin and ouabain, their intracellular effects are thought to be markedly different. 32,33 Unlike ouabain, digoxin is able to pass through the cell membrane whereby it binds to ryanodine receptors. 34 Once bound, Ca 2 + is released from the sarcoplasmic reticulum.…”

Section: Introductionmentioning

confidence: 99%

Digoxin and Adenosine Triphosphate Enhance the Functional Properties of Tissue-Engineered Cartilage

Makris

Huang

et al. 2015

Tissue Engineering Part A

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Toward developing engineered cartilage for the treatment of cartilage defects, achieving relevant functional properties before implantation remains a significant challenge. Various chemical and mechanical stimuli have been used to enhance the functional properties of engineered musculoskeletal tissues. Recently, Ca 2 + -modulating agents have been used to enhance matrix synthesis and biomechanical properties of engineered cartilage. The objective of this study was to determine whether other known Ca 2 + modulators, digoxin and adenosine triphosphate (ATP), can be employed as novel stimuli to increase collagen synthesis and functional properties of engineered cartilage. Neocartilage constructs were formed by scaffold-free self-assembling of primary bovine articular chondrocytes. Digoxin, ATP, or both agents were added to the culture medium for 1 h/ day on days 10-14. After 4 weeks of culture, neocartilage properties were assessed for gross morphology, biochemical composition, and biomechanical properties. Digoxin and ATP were found to increase neocartilage collagen content by 52-110% over untreated controls, while maintaining proteoglycan content near native tissue values. Furthermore, digoxin and ATP increased the tensile modulus by 280% and 180%, respectively, while the application of both agents increased the modulus by 380%. The trends in tensile properties were found to correlate with the amount of collagen cross-linking. Live Ca 2 + imaging experiments revealed that both digoxin and ATP were able to increase Ca 2 + oscillations in monolayer-cultured chondrocytes. This study provides a novel approach toward directing neocartilage maturation and enhancing its functional properties using novel Ca 2 + modulators.

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On the Differences Between Ouabain and Digitalis Glycosides

Cited by 40 publications

References 56 publications

Rethinking Heart Failure

Rethinking Heart Failure

Antiviral Screening of Multiple Compounds against Ebola Virus

Digoxin and Adenosine Triphosphate Enhance the Functional Properties of Tissue-Engineered Cartilage

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