Abstract
Cardioactive glycosides, like digoxin, ouabain and related compounds, are drugs that inhibit Na+/K+-ATPase and have a strong inotropic effect on heart: they cause the Na+/Ca2+ exchanger to extrude Na+ in exchange with Ca2+ and therefore increase the [Ca2+]i concentration. For this reason, some of these drugs are currently used in the treatment of congestive heart failure and cardiac arrhythmias. Recently it has been discovered that cardiac glycosides exert pleiotropic effects on many aspects of cell metabolism. Na+/K+-ATPase is not the exclusive target, as they affect the cell response to hypoxia, modulate several signaling pathways involved in cell death and proliferation, regulate the transcription of different genes and modify the pharmacokinetics of other drugs, by altering the expression and activity of drug-metabolizing enzymes. Some of these effects are related to the steroid structure of glycosides, a property which also makes them fine modulators of the synthesis of cholesterol and steroid hormones. Moreover, new endogenously synthesized glycosides have been discovered in the last years: these molecules are involved in the balance of salt and in the control of blood pressure.
This review will focus on the recent studies which have demonstrated that exogenous and endogenous glycosides, besides playing a role as inotropic agents, are also important in the pathogenesis and therapy of different human diseases, such as stroke, diabetes, neurological diseases and cancer.
Keywords: Digoxin, ouabain, Na+/K+-ATPase, cancer, sterols metabolism, Cardioactive glycosides, cardiac arrhythmias, pleiotropic effects, roliferation
Current Medicinal Chemistry
Title: Pleiotropic Effects of Cardioactive Glycosides
Volume: 18 Issue: 6
Author(s): C. Riganti, I. Campia, J. Kopecka, E. Gazzano, S. Doublier, E. Aldieri, A. Bosia and D. Ghigo
Affiliation:
Keywords: Digoxin, ouabain, Na+/K+-ATPase, cancer, sterols metabolism, Cardioactive glycosides, cardiac arrhythmias, pleiotropic effects, roliferation
Abstract: Cardioactive glycosides, like digoxin, ouabain and related compounds, are drugs that inhibit Na+/K+-ATPase and have a strong inotropic effect on heart: they cause the Na+/Ca2+ exchanger to extrude Na+ in exchange with Ca2+ and therefore increase the [Ca2+]i concentration. For this reason, some of these drugs are currently used in the treatment of congestive heart failure and cardiac arrhythmias. Recently it has been discovered that cardiac glycosides exert pleiotropic effects on many aspects of cell metabolism. Na+/K+-ATPase is not the exclusive target, as they affect the cell response to hypoxia, modulate several signaling pathways involved in cell death and proliferation, regulate the transcription of different genes and modify the pharmacokinetics of other drugs, by altering the expression and activity of drug-metabolizing enzymes. Some of these effects are related to the steroid structure of glycosides, a property which also makes them fine modulators of the synthesis of cholesterol and steroid hormones. Moreover, new endogenously synthesized glycosides have been discovered in the last years: these molecules are involved in the balance of salt and in the control of blood pressure.
This review will focus on the recent studies which have demonstrated that exogenous and endogenous glycosides, besides playing a role as inotropic agents, are also important in the pathogenesis and therapy of different human diseases, such as stroke, diabetes, neurological diseases and cancer.
Export Options
About this article
Cite this article as:
Riganti C., Campia I., Kopecka J., Gazzano E., Doublier S., Aldieri E., Bosia A. and Ghigo D., Pleiotropic Effects of Cardioactive Glycosides, Current Medicinal Chemistry 2011; 18 (6) . https://dx.doi.org/10.2174/092986711794927685
DOI https://dx.doi.org/10.2174/092986711794927685 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Recent Advances in the Development of Multi-Kinase Inhibitors
Mini-Reviews in Medicinal Chemistry Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses
Recent Patents on Anti-Cancer Drug Discovery Cytotoxicity and Toxicity to Animals and Humans of Ribosome-Inactivating Proteins
Mini-Reviews in Medicinal Chemistry Growth Arrest Specific Gene (GAS) 6 Modulates Platelet Thrombus Formation and Vascular Wall Homeostasis and Represents an Attractive Drug Target
Current Pharmaceutical Design HCN Pacemaker Channels and Pain: A Drug Discovery Perspective
Current Pharmaceutical Design Role of Magnetic Resonance Imaging in Myocardial Iron Assessment
Current Cardiology Reviews Novel Findings and Therapeutic Targets on Cardioprotection of Ischemia/ Reperfusion Injury in STEMI
Current Pharmaceutical Design Management of Spasticity in Progressive Multiple Sclerosis: Efficacy of Repeated Intrathecal Triamcinolone Acetonide Administration
Current Pharmaceutical Design Chemokines and Atherosclerotic Plaque Progression: Towards Therapeutic Targeting?
Current Pharmaceutical Design Chemokines as Potential Therapeutic Targets in Atherosclerosis
Current Drug Targets Protein-Energy Malnutrition Alters Hippocampal Plasticity-Associated Protein Expression following Global Ischemia in the Gerbil
Current Neurovascular Research Pharmacological Therapy of Parkinson’s Disease: Current Options and New Avenues
Recent Patents on CNS Drug Discovery (Discontinued) Statins and Cancer
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Drugs that Slow the Heart Rate of Early Rat Embryos. Is there a Risk for the Human?
Current Pharmaceutical Design Role of Oxidative-Nitrosative Stress and Downstream Pathways in Various Forms of Cardiomyopathy and Heart Failure
Current Vascular Pharmacology C. elegans Genetic Networks Predict Roles for O-GlcNAc Cycling in Key Signaling Pathways
Current Signal Transduction Therapy Pharmacotherapy for Patent Ductus Arteriosus: Current Options and Outstanding Questions
Current Pediatric Reviews Biomarkers in Molecularly Targeted Therapy for Cancer
Recent Patents on Biomarkers Editorial [ Nuclear Receptors as Drug Discovery Targets Executive Editor: Sunil Nagpal ]
Mini-Reviews in Medicinal Chemistry Pharmacological Risk Factors for Delirium after Cardiac Surgery: A Review
Current Neuropharmacology