Abstract
Mitochondria have long been involved in several cellular processes beyond its role in energy production. The importance of this organelle for cardiac tissue homeostasis has been greatly investigated and its impairment can lead to cell death and consequent organ failure. Several compounds have been described in the literature as having direct effects on cardiac mitochondria which can provide a mechanistic explanation for their toxicological or pharmacological effects. The present review describes one classic example of druginduced cardiac mitochondrial toxicity and another case of drug-induced mitochondrial protection. For the former, we present the case of doxorubicin, an anticancer agent whose treatment is associated with a cumulative and dose-dependent cardiomyopathy with a mitochondrial etiology. Following this, we present the case of carvedilol, a β-blocker with intrinsic antioxidant activity, which has been described to protect cardiac mitochondria from oxidative injury. The final part of the review integrates information from the previous chapters, demonstrating how carvedilol can contribute to reduce doxorubicin toxicity on cardiac mitochondria. The two referred examples result in important take-home messages: a) drug-induced cardiac mitochondrial dysfunction is an important contributor for drug-associated organ failure, b) protection of mitochondrial function is involved in the beneficial impact of some clinically-used drugs and c) a more accurate prediction of toxic vs. beneficial effects should be an important component of drug development by the pharmaceutical industry.
Keywords: Cardioprotection, carvedilol, doxorubicin, heart, mitochondria, toxicity, oxidative stress, apoptosis, metalloproteinases, anthracyclines
Current Pharmaceutical Design
Title: Drug-induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol
Volume: 17 Issue: 20
Author(s): Goncalo C. Pereira, Ana M. Silva, Catia V. Diogo, Filipa S. Carvalho, Pedro Monteiro and Paulo J. Oliveira
Affiliation:
Keywords: Cardioprotection, carvedilol, doxorubicin, heart, mitochondria, toxicity, oxidative stress, apoptosis, metalloproteinases, anthracyclines
Abstract: Mitochondria have long been involved in several cellular processes beyond its role in energy production. The importance of this organelle for cardiac tissue homeostasis has been greatly investigated and its impairment can lead to cell death and consequent organ failure. Several compounds have been described in the literature as having direct effects on cardiac mitochondria which can provide a mechanistic explanation for their toxicological or pharmacological effects. The present review describes one classic example of druginduced cardiac mitochondrial toxicity and another case of drug-induced mitochondrial protection. For the former, we present the case of doxorubicin, an anticancer agent whose treatment is associated with a cumulative and dose-dependent cardiomyopathy with a mitochondrial etiology. Following this, we present the case of carvedilol, a β-blocker with intrinsic antioxidant activity, which has been described to protect cardiac mitochondria from oxidative injury. The final part of the review integrates information from the previous chapters, demonstrating how carvedilol can contribute to reduce doxorubicin toxicity on cardiac mitochondria. The two referred examples result in important take-home messages: a) drug-induced cardiac mitochondrial dysfunction is an important contributor for drug-associated organ failure, b) protection of mitochondrial function is involved in the beneficial impact of some clinically-used drugs and c) a more accurate prediction of toxic vs. beneficial effects should be an important component of drug development by the pharmaceutical industry.
Export Options
About this article
Cite this article as:
C. Pereira Goncalo, M. Silva Ana, V. Diogo Catia, S. Carvalho Filipa, Monteiro Pedro and J. Oliveira Paulo, Drug-induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol, Current Pharmaceutical Design 2011; 17 (20) . https://dx.doi.org/10.2174/138161211796904812
DOI https://dx.doi.org/10.2174/138161211796904812 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Target-based Anti-angiogenic Therapy in Breast Cancer
Current Pharmaceutical Design Inflammatory Related Cardiovascular Diseases: From Molecular Mechanisms to Therapeutic Targets
Current Pharmaceutical Design Cell Sheet-Based Myocardial Tissue Engineering: New Hope for Damaged Heart Rescue
Current Pharmaceutical Design Targeting microRNAs in Pathological Hypertrophy and Cardiac Failure
Mini-Reviews in Medicinal Chemistry Adipose Triglyceride Lipase: A New Target in the Regulation of Lipolysis by Insulin
Current Diabetes Reviews Autoantibodies for Cardiac Channels and Sudden Cardiac Death and its Relationship to Autoimmune Disorders
Current Cardiology Reviews Combined Anticancer Therapies: An Overview of the Latest Applications
Anti-Cancer Agents in Medicinal Chemistry The Oxido-reductase Activity of the Apoptosis Inducing Factor: A Promising Pharmacological Tool?
Current Pharmaceutical Design Potential Role of TRAIL in the Management of Autoimmune Diabetes Mellitus
Current Pharmaceutical Design Novel approaches to examine the regulation of voltage-gated calcium channels in the heart
Current Molecular Pharmacology Editorial [Hot Topic: Matrix Metalloproteinases in Cardiovascular Disease (Guest Editors: N. Papageorgiou & D. Tousoulis)]
Current Topics in Medicinal Chemistry Current State of Development of Genome Analysis in Livestock
Current Genomics The Emerging Roles of Leptin and Ghrelin in Cardiovascular Physiology and Pathophysiology
Current Vascular Pharmacology Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiac Structural and Electrical Remodeling: From Myocardial Cytology to Cardiodiabetology
Current Vascular Pharmacology Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes
Current Pharmaceutical Design Comparison of Uptake Mechanisms for Anthracyclines in Human Leukemic Cells
Current Drug Delivery Adverse Cardiovascular Effects of Antirheumatic Drugs: Implications for Clinical Practice and Research
Current Pharmaceutical Design Understanding Abnormal c-JNK/p38MAPK Signaling in Amyotrophic Lateral Sclerosis: Potential Drug Targets and Influences on Neurological Disorders
CNS & Neurological Disorders - Drug Targets Cell-free DNA: Characteristics, Detection and its Applications in Myocardial Infarction
Current Pharmaceutical Design Proteomic and Bioinformatic Analysis of Trypanosoma cruzi Chemotherapy and Potential Drug Targets: New Pieces for an Old Puzzle
Current Drug Targets