Induction of drug (xenobiotic)-metabolizing enzymes is a common biological response to xenobiotics, the mechanisms and consequences of which are important in academic, industrial, and regulatory areas of pharmacology and toxicology. This monograph, for the first time, has brought together researchers who deal specifically with drug-metabolizing enzymes and peroxisome proliferators. It contains an up-to-date review of peroxisome proliferation, with detailed tables on the 100 known peroxisome proliferators and studies on their hepatocarcinogic capacity. It provides current material from 12 different laboratories doing cutting-edge research on the effect of peroxisome proliferators on drug-metabolizing enzymes.The book covers the response of cytochrome P450s, UDP-glucuronosyltransferases, epoxide hydrolases, glutathione S-transferase, DT-diaphorase, and other enzymes.
A state-of-the-art consensus report on what is known about peroxisome proliferation, the mechanisms involved, and their relevance to carcinogenesis. Peroxisomes are single, membrane-limited, cytoplasmic organelles that are found in cells of animals, plants, fungi, and protozoa. Peroxisome proliferators include certain hypolipidaemic drugs, phthalate ester plasticizers, industrial solvents, herbicides, food flavours, leukotriene D4 antagonists, and hormones. Numerous studies in rats and mice have demonstrated the hepatocarcinogenic effects of peroxisome proliferators, and these compounds have been unequivocally established as carcinogens. Since humans are exposed to peroxisome proliferators to a significant extent, assessment of the adverse biological effects of this group of compounds, and particularly their potential carcinogenicity, has become an important issue. The report has two parts. The first records the consensus reached by a group of eleven experts, including several of the leading investigators in this field. Questions addressed include the mechanisms by which peroxisome proliferators exert their carcinogenic effects in rodents, the relevance of animal studies to the evaluation of carcinogenic risk in humans, and the potential use of peroxisome proliferation as a biological marker for liver cancer. The report concludes that compounds inducing peroxisome proliferation in rats and mice have little, if any, effect on human liver. The report also issues advice on the interpretation of peroxisome proliferation, demonstrated in animal studies, when evaluating the carcinogenic risk to humans. The second part consists of three background papers presented by members of the working group.
All three peroxisome proliferator-activated receptor (PPAR) subtypes share a high degree of structural homology while exhibiting differences in function, tissue distribution, and ligand specificity. In Peroxisome Proliferator-Activated Receptors: Discovery and Recent Advances, the authors trace the history of PPAR discovery and detail the receptor structure and its posttranslational modifications. Furthermore, endogenous ligands as well as various classes of exogenous ligands, subtype-selective, dual and pan agonists as well as antagonists, are discussed. In addition, the tissue distribution and versatile functions of PPAR subtypes in major organs are described. As PPARs play critical roles as regulators of numerous physiological as well as pathophysiological pathways, Peroxisome Proliferator-Activated Receptors: Discovery and Recent Advances aims to help researchers to develop safer and more effective PPAR modulators as therapeutic agents to treat a myriad of diseases and conditions.
In Vitro Methods in Pharmaceutical Research provides a comprehensive guide to laboratory techniques for evaluating in vitro organ toxicity using cellular models. Step-by-step practical tips on how to perform and interpret assays for drug metabolism and toxicity assessment are provided, along with a comparison of different techniques available. It is a welcome addition to the literature at a time when interest is growing in cellular in vitro models for toxicology and pharmacology studies. - Meets the continuing demand for information in this field - Compares In Vitro techniques with other methods - Describes cell-culture methods used to investigate toxicity in cells derived from different organs - Includes contributions by leading experts in the field
Worldwide, the prevalence of chronic diseases, such as obesity, diabetes, cardiovascular diseases, cancer, non-alcoholic fatty liver disease, inflammatory (autoimmune) and neurodegenerative diseases, has shown a sharp increase. In the last 20 years, developing countries and the young population have presented the largest augment in the incidence of these diseases, which evidences that they are not only limited to developed countries nor the adult population. These pathologies have in common a complex interaction between genetic, metabolic and environmental factors. In this context, several basic and clinical researches have demonstrated the relevance of the expression and activity of the peroxisomal proliferator-activated receptors (PPARs) as fundamental elements in the prevention and treatment of chronic diseases. PPARs are a family of transcription factors that control many cellular metabolic processes. PPAR isoform expression and activity is regulated in different tissues according to physiological processes (growth, development, and aging) and to pathological conditions (cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, hepatic diseases, among others). Also, different compounds such as drugs (fibrates), nutrients (long-chain polyunsaturated fatty acids), and several natural bioactive compounds (polyphenols) are molecular regulators of PPARs expression and activity. Recent research has established the importance of the regulation of PPARs activity and their role in cell and tissue protection against injury (i.e., oxidative stress, inflammation, endoplasmic reticulum stress). This book is dedicated to reviewing the state of the art regarding PPARs regulation with an emphasis on molecular aspects underlying their effect in health and disease. Specifically, the participation of PPARs is discussed in insulin resistance, inflammation, NAFLD, DM2, cardiovascular disease, hypertension, obesity, gastrointestinal disease, and neurological health and disease. Moreover, this book reviews how different molecules regulate the expression and activity of PPARs. Finally, the scientific information presented in this book pretends to contribute to a greater understanding of PPAR role in the prevention and treatment of different pathologies and metabolic alterations.
Handbook of Epigenetics: The New Molecular and Medical Genetics, Second Edition, provides a comprehensive analysis of epigenetics, from basic biology, to clinical application. Epigenetics is considered by many to be the new genetics in that many biological phenomena are controlled, not through gene mutations, but rather through reversible and heritable epigenetic processes. These epigenetic processes range from DNA methylation to prions. The biological processes impacted by epigenetics are vast and encompass effects in lower organisms and humans that include tissue and organ regeneration, X-chromosome inactivation, stem cell differentiation, genomic imprinting, and aging. The first edition of this important work received excellent reviews; the second edition continues its comprehensive coverage adding more current research and new topics based on customer and reader reviews, including new discoveries, approved therapeutics, and clinical trials. From molecular mechanisms and epigenetic technology, to discoveries in human disease and clinical epigenetics, the nature and applications of the science is presented for those with interests ranging from the fundamental basis of epigenetics, to therapeutic interventions for epigenetic-based disorders. - Timely and comprehensive collection of fully up-to-date reviews on epigenetics that are organized into one volume and written by leading figures in the field - Covers the latest advances in many different areas of epigenetics, ranging from basic aspects, to technologies, to clinical medicine - Written at a verbal and technical level that can be understood by scientists and college students - Updated to include new epigenetic discoveries, newly approved therapeutics, and clinical trials
A new volume in the Methods in Molecular Biology series, this book includes cutting-edge methods and advice for characterizing PPARs, reflecting their critical roles as regulators of numerous physiological as well as pathophysiological pathways.
The first of its kind, this reference gives a comprehensive but concise introduction to epigenetics before covering the many interactions between hormone regulation and epigenetics at all levels. The contents are very well structured with no overlaps between chapters, and each one features supplementary material for use in presentations. Throughout, major emphasis is placed on pathological conditions, aiming at the many physiologists and developmental biologists who are familiar with the importance and mechanisms of hormone regulation but have a limited background in epigenetics.
Provides an update on several new aspects of peroxisome biology, including the role of the peroxisome proliferator activated receptor. The book covers morphilogical, biochemical and molecular biological aspects of peroxisomes.
