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Developed as a one-stop reference source for drug safety and toxicology professionals, this book explains why mitochondrial failure is a crucial step in drug toxicity and how it can be avoided. • Covers both basic science and applied technology / methods • Allows readers to understand the basis of mitochondrial function, the preclinical assessments used, and what they reveal about drug effects • Contains both in vitro and in vivo methods for analysis, including practical screening approaches for drug discovery and development • Adds coverage about mitochondrial toxicity underlying organ injury, clinical reports on drug classes, and discussion of environmental toxicants affecting mitochondria
This special book is conceived to highlight mitochondrial structural and functional integrity and how they are associated with several human diseases such as cardiovascular, cancer, renal, neurological disorder, and genetic disorders. The chapters contributed by leading mitochondrial researchers in the handbook will take us through the novel pharmacological strategies via mitochondria to understand their physiological and pathological role as well as present them as therapeutic targets.
Mitochondrial Metabolism: An Approach for Disease Management covers mitotherapy from three combined perspectives, Pharmacology, Toxicology and Biochemistry. After an introduction from world-renowned experts, the book's chapters cover the balancing role in reduction/oxidation mitochondria play, mitochondria as targets for therapeutics through its metabolism, mitochondrial contributions to the cell death process, mitochondrial response to environmental toxicants, the mitochondrial role in aging, the impact of calorie restrictive diets, new advances in the identification of altered mitochondria associated signaling pathways in carcinogenesis, and much more. This book provides bioscientists new horizons to realize the importance of mitochondria in present-day research on therapies dealing with mitochondria associated chronic diseases, including diabetes, cancer and neurodegenerative disorders. Details the significant role of mitochondria in chronic diseases Presents new insights on the targeting of mitochondria for therapeutic purposes Includes updated results on mitotherapy and other mitochondria-oriented therapies
This is the definitive, one-stop resource on preclinical drug evaluation for potential mitochondrial toxicity, addressing the issue upfront in the drug development process. It discusses mitochondrial impairment to organs, skeletal muscle, and nervous systems and details methodologies used to assess mitochondria function. It covers both in vitro and in vivo methods for analysis and includes the latest models. This is the authoritative reference on drug-induced mitochondrial dysfunction for safety assessment professionals in the pharmaceutical industry and for pharmacologists and toxicologists in both drug and environmental health sciences.
Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
The increased exposure to toxins, toxicants and novel drugs has promoted toxicology to become one of the most important areas of research with emerging innovative toxicity testing protocols, techniques, and regulation being placed. Since the bioactivation of many toxins and toxicants and its consequences on human health are not clearly known, this book offers a quick overview of cellular toxicology through the cell, drug and environmental toxicity. This book does not strive to be comprehensive but instead offers a quick overview of principle aspects of toxins and toxicants in order to familiarize the key principles of toxicology. The book is divided into three main sections,; the first one discusses the role of mitochondrial dysfunction, oxidative stress and mitochondrial drug development. The second and third sections bring light to forensic toxicology and drug poisoning followed by environmental toxicity.
Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.
This book addresses the therapeutic strategies to target mitochondrial metabolism in diseases where the function of that organelle is compromised, and it discusses the effective strategies used to create mitochondrial-targeted agents that can become commercially available drug delivery platforms. The consistent growth of research focused in understanding the multifaceted role of mitochondria in cellular metabolism, controlling pathways related with cell death, and ionic/redox regulation has extended the research of mitochondrial chemical-biological interactions to include various pharmacological and toxicological applications. Not only does the book extensively cover basic mitochondrial physiology, but it also links the molecular interactions within these pathways to a variety of diseases. It is one of the first books to combine state-of-the-art reviews regarding basic mitochondrial biology, the role of mitochondrial alterations in different diseases, and the importance of that organelle as a target for pharmacological and non-pharmacological interventions to improve human health. The different chapters highlight the chemical-biological linkages of the mitochondria in context with drug development and clinical applications.
This expert volume covers an interdisciplinary and rapidly growing area of biomedical research comprising genetic, biochemical, pathological, and clinical studies aimed at the diagnosis and therapy of human diseases which are either caused by or associated with mitochondrial dysfunction. It dedicates itself to showcasing the tremendous efforts and the progress that has been made over the last decades in developing techniques and protocols for probing, imaging, and manipulating mitochondrial functions. Mitochondrial Medicine: Volume II, Manipulating Mitochondrial Function describes techniques developed for manipulating and assessing mitochondrial function under general pathological conditions and specific disease states. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Mitochondrial Medicine provides an essential source of know-how and inspiration to all researchers who are fascinated by this tiny organelle that seems so clearly to control the life and death of a single cell and whole organisms alike.