- Tapa blanda: 344 páginas
- Editor: CRC Press; Edición: 1 (24 de octubre de 2002)
- Idioma: Inglés
- ISBN-10: 0415284597
- ISBN-13: 978-0415284592
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Mechanistic Toxicology: The Molecular Basis of How Chemicals Disrupt Biological Targets (Inglés) Tapa blanda – 24 oct 2002
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'Students taking formal training in toxicology would definitely benefit from adding this book to their collection, since it covers many recent advances in the field.' - British Toxicology Society Newsletter
'This recently-published volume is a clear state-of-the-art explanation and description of how chemicals disrupt biological targets on a molecular basis. It is a beauty!'. - Toxicology Letters
Reseña del editor
Reductionism to cellular and molecular mechanisms is one of the cornerstones of modern toxicology, forming the basis for a better understanding of individual toxic effects, and providing an important tool for human risk assessment. Mechanistic Toxicology is a timely textbook that provides an introduction to this important, but often neglected, area within the toxicological sciences. This book gives new insights into the processes and mechanisms underlying the toxicity of chemicals and explains how foreign compounds (drugs, environmental pollutants, industrial chemicals) exert their potentially damaging effects on cells and tissues.
*an extensive number of illustrations, tables and photographs
*summaries of the main learning points
*question and answer reviews at the end of each chapter
Mechanistic Toxicology incorporates recent advances in molecular biology and develops concepts for the reader in a logical way. It also illustrates, using many examples and complementary background information, how a better understanding of these mechanistic pathways helps in estimating potential risk to human health. Ideal for use in undergraduate and graduate classes of pharma-toxicology and environmental toxicology, Mechanistic Toxicology is also a valuable reference for any other readers interested in this subject.
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In the five years since the first edition was published there have been majot advances in virtually every aspect of the field. As a result each chapter has been updated and new chapters added.
Although an introductory book on the subject, this book is intended for the advanced undergraduate or beginning graduate level student. Of course it might also be used by specialists in other areas needing information about the subject. To further this usage, there is an extensive bibliography of papers at the end of each chapter.
Chapters are structured to present the topics first in the "Contents" section, dive deeper into each topic with helpful headings and examples, summarize and simplify what was presented in the "Learning Points" section, and lastly, to suggest further reading. Examples provided in the body of each chapter can get highly technical, though the main points of the chapter are never lost in even the most extended example.
The abundance of examples and in-depth discussions on specific mechanisms makes this book optimal for someone who already has some background in biology and an understanding of toxicological concepts. The reader who hopes to develop a basic understanding of toxicology should look elsewhere, unless that reader is willing to commit substantial amounts of time pulling the basics out of the somewhat technical contents of this book
Finally, the review question and answer section in the back of the book and the index are useful tools that demonstrate the author's ability to make technical concepts more understandable, considering that the reader has some background in related topics. The book is well equipped to explain concepts that may be beyond that reader's understanding.
Below, the title and a summary sentence is given for each chapter.
An overview of what toxicology investigates and the meaning/importance of both toxicokinetics and toxicodynamics.
Ch. 2. Organ-selective Toxicity
Organ-selective toxicity is based on some of the toxicokinetic and toxicodynamic factors discussed in the previous chapter.
Ch. 3 Cellular Transport and Selective Accumulation of Potentially Toxic Xenobiotics
Structures and the properties resulting from structure of substances, coupled with transport proteins and membrane composition, determine if a xenobiotic can enter a cell and remain there long enough to demonstrate toxic effects.
Ch. 4 Bioactivation of Xenobiotics and Reactive Metabolites
Toxicity is often induced when a substance is metabolized from its original form.
Ch. 5 Xenobiotic-induced Oxidative Stress: Cell Injury, Signaling, and Gene Regulation
Oxidative species are created all the time in equilibrium with antioxidants, but when the equilibrium favors oxidative species (ROS, RNS) cell damage occurs.
Ch. 6 Disruption of Cellular Calcium Homeostasis
Calcium is critical in regulating cell metabolism, activating enzymes and other proteins, and acting as a second messenger, but different xenobiotics can interfere with calcium in all of these processes.
Ch. 7 Mechanisms of Necrotic and Apoptotic Cell Death
Necrosis is relatively random and unorganized cell death, whereas apoptosis is organized cell death that involves signals received by death receptors, action by caspases and checkpoints along the way.
Ch. 8 Impairment of Cell proliferation and Tissue Repair
Xenobiotics and induce or impair cell proliferation.
Ch. 9 Covalent Binding of Reactive Metabolites to Cellular Macromolecules
Some Xenobiotics can be activated into an electrophile that reacts with protein or DNA nucleophiles, forming covalent bonds.
Ch. 10 Immune Mechanisms
Xenobiotics can inhibit immune response, increasing chances of infection, or increase immune response, causing damage through autoimmune action.
Ch. 11 Cytokine-mediated Toxicity
Proinflammatory cytokines and chemokines can enhance or mediate toxicity.
Ch. 12 Specific Inactivation of Enzymes and Other Proteins
Some xenobiotics target very specific proteins, organophosphates being a good example of this in their tendency to target acetylcholine esterase.
Ch. 13 Nuclear Receptor-Mediated Toxicity
Some xenobiotics can bind to nuclear receptors and disrupt normal processes.
Ch. 14 Interactions of Xenobiotics With Ion Transporters
Some xenobiotics can bind to ion channels and ion pumps, disrupting critical functions, like the action of sodium-potassium pumps.
Ch. 15 Disruption of Cellular Energy Production by Xenobiotics
Xenobiotics interference of mitochondrial activity results in a cellular energy crisis and can add to the production of ROS (addressed in Ch. 5).
Ch. 16 Outlook: From Mechanisms to Individual Expression of Genes
Major advances including DNA sequencing and advances in molecular technology is helping provide massive quantities of data still requiring interpretation.
The author, Urs A. Boelsterli, currently serves at the Chair in Mechanistic Toxicology in the Department of Pharmaceutical Sciences at the University of Conneticut. He earned a M. Sc. And Ph. D. from the University of Zurich and did his postdoctoral work at the University of Toxicology in Zurich, Switzerland. His most recent publication, Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice, was published in 2012. He is also on the editorial board of Toxicology Mechanisms and Methods.