Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: a pilot study (original) (raw)
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Oxidative medicine and cellular longevity, 2014
Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF i...
Role of Mitochondrial Dysfunction in Related Diseases-A Review
Journal of health and rehabilitation research, 2024
Background: Mitochondrial dysfunction (MD) is increasingly recognized for its role in a wide array of diseases, extending beyond primary mitochondrial diseases (PMDs) to include secondary mitochondrial diseases (SMDs) and a broad spectrum of neurodegenerative, cardiovascular, metabolic, and oncological disorders. This growing awareness underscores the need for a comprehensive review of the mechanisms underlying MD, its clinical implications, and emerging therapeutic strategies. Objective: To synthesize current knowledge on the pathogenesis of diseases associated with MD, delineate the distinction between PMDs and SMDs, explore the genetic and environmental factors contributing to MD, and assess the potential of novel therapeutic approaches targeting mitochondrial dysfunction. Methods: A narrative review was conducted through a structured search of PubMed, Scopus, Web of Science, and Google Scholar, focusing on articles published up to April 2023. Keywords related to mitochondrial dysfunction and its implications across various diseases were used to identify relevant studies. Inclusion criteria targeted original research, reviews, and meta-analyses published in English that contributed to understanding MD's role in disease pathogenesis and treatment. Data extraction and synthesis were performed to highlight key findings, mechanisms, and therapeutic strategies. Results: The review emphasizes the critical role of mitochondrial dysfunction in the pathogenesis of a wide range of diseases. It identifies specific mtDNA mutations contributing to PMDs and highlights how SMDs arise from mitochondrial impairment secondary to other conditions. The synthesis of findings points to oxidative stress, impaired ATP production, and altered mitochondrial dynamics as central to MD's impact on cellular and systemic health. Additionally, the review explores emerging therapies, including mitochondrial-targeted antioxidants, gene therapy, and metabolic interventions, underscoring their potential in managing MDrelated diseases. Conclusion: Mitochondrial dysfunction is a pivotal factor in the etiology of numerous diseases, with genetic mutations and environmental influences contributing to its development and progression. Understanding these complex mechanisms is essential for devising effective therapeutic interventions. While significant advances have been made, further research is needed to fully exploit the therapeutic potential of targeting mitochondrial dysfunction.
Mitochondrial dysfunction and molecular pathways of disease
2007
Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. Antioxidant therapies hold promise for improving mitochondrial performance. Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them. If in the next 50 years advances in mitochondrial treatments match the immense increase in knowledge about mitochondrial function that has occurred in the last 50 years, mitochondrial diseases and dysfunction will largely be a medical triumph.
Mitochondrial Oxidative Stress—A Causative Factor and Therapeutic Target in Many Diseases
International Journal of Molecular Sciences, 2021
The excessive formation of reactive oxygen species (ROS) and impairment of defensive antioxidant systems leads to a condition known as oxidative stress. The main source of free radicals responsible for oxidative stress is mitochondrial respiration. The deleterious effects of ROS on cellular biomolecules, including DNA, is a well-known phenomenon that can disrupt mitochondrial function and contribute to cellular damage and death, and the subsequent development of various disease processes. In this review, we summarize the most important findings that implicated mitochondrial oxidative stress in a wide variety of pathologies from Alzheimer disease (AD) to autoimmune type 1 diabetes. This review also discusses attempts to affect oxidative stress as a therapeutic avenue.
Mediterranean Journal of Hematology and Infectious Diseases, 2020
Structural mitochondrial abnormalities as well as genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS) , yet there is currently little data regarding the metabolic properties and energy production of MDS cells. In the current study we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls We then assessed the effect of food supplements- Coenzyme Q10 and carnitine on mitochondrial function and hematological response .We show here for the first time that in low risk MDS there is a significant impairment of mitochondrial respiration in peripheral blood cells and this can be improved with food supplements. We also show that such myelodysplastic syndrome, mitochondria, oxidative phosphorylation, coenzyme Q10, seahorse XF analyzer. supplements lead to improvement in cytopenia's and quality of life.
Mitochondrial oxidative stress and mammalian healthspan
2010
Aging of the American society is leading to a growing need for disease-modifying interventions to treat age-related diseases and enhance healthspan. Mitochondria and mitochondrially-generated reactive oxygen species appear to play a central role in these processes and are a likely target for interventions. Conventional, untargeted antioxidants have not demonstrated a clear benefit in human studies. As a result, approaches have been developed to target antioxidants specifically to mitochondria. Studies have employed a wide array of targeted molecules including antioxidant enzymes such as catalase, peroxiredoxin, superoxide dismutases and small molecular compounds which recapitulate the antioxidant activities of these enzymes. Lifespan and healthspan effects differ between interventions suggesting varied roles for specific mitochondrial reactive oxygen species and their impact on usual aging. Consistent findings in myocardial protection across various interventions support a focus on the impact of cardiac aging on healthspan. The advancement of mitochondriallytargeted small molecule antioxidants suggests the prospect of swift translation to human use.