The CYP P450 gene family is the largest group of drug metabolizing enzymes, accounting for the metabolism of 75% of all drugs and toxins.
Author: Katherine Joubin
Category: Cytochrome P-450
The CYP P450 gene family is the largest group of drug metabolizing enzymes, accounting for the metabolism of 75% of all drugs and toxins. CYP genes are highly polymorphic, with hundreds of alleles that directly affect enzymatic activity. In order to assess the functional relevance of these genetic polymorphisms on an individual's response to a particular drug, human population studies, animal models, and hepatocyte cell cultures have been used to study how CYP enzymes function and are regulated. Here I show that human embryonic stem (hES) cells can also be used to study the complex signaling pathways that regulate CYP expression and activity. Using previously published liver differentiation protocols for guidance, I developed a simplified protocol using Activin, Bone Morphogenetic Protein-4, and Hepatocyte Growth Factor that effectively differentiates hES cells into endodermal cells that develop into liver cells. The efficiency of differentiation was monitored by immunohistochemistry and PCR for various liver markers such as alpha-fetoprotein, CYP 2C9, CYP 3A4, and CYP 3A7. These liver cells were then treated with the anti-convulsant drug phenytoin and the antimycobiotic drug rifampin. The effect of these drugs on CYP gene expression was then measured by quantitative PCR. I found that rifampin, but not phenytoin, is able to induce the expression of CYP 2C9. My results show that liver cells produced from hES cells are able to regulate gene expression in response to drugs. Using hES cells can therefore provide a powerful and efficient model system to study the regulation of drug metabolizing enzymes and the genetic components that control drug induced signaling.
It aims to: enable the practitioner to assess liver function using biochemical markers, other tests, signs, symptoms and disease knowledge; identify which pharmacokinetic and pharmacodynamic parameters of a drug are likely to be affected by ...
Author: Penny North-Lewis
Liver disease is a widespread and increasing problem throughout the world, however little is published on how different types and degrees of liver dysfunction affect the body's ability to handle medicines."Drugs and the Liver" is designed to assist practitioners in making pragmatic choices for their patients. It aims to: enable the practitioner to assess liver function using biochemical markers, other tests, signs, symptoms and disease knowledge; identify which pharmacokinetic and pharmacodynamic parameters of a drug are likely to be affected by different types of liver disease; and consider the impact of a drug's side effects on a patient with liver disease.This practical guide covers background information on liver function, the principles of drug use in liver disease and includes a section of worked examples of commonly asked questions. It will be invaluable to clinical pharmacists and anyone making medicine choices in patients with liver impairment.
Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity.
Author: Hyman J. Zimmerman
Publisher: Lippincott Williams & Wilkins
Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity. Dr. Zimmerman examines the interface between chemicals and the liver; the latest research in experimental hepatotoxicology; the hepatotoxic risks of household, industrial, and environmental chemicals; and the adverse effects of drugs on the liver. This thoroughly revised, updated Second Edition features a greatly expanded section on the wide variety of drugs that can cause liver injury. For quick reference, an appendix lists these medications and their associated hepatic injuries. Also included are in-depth discussions of drug metabolism and factors affecting susceptibility to liver injury.
This new volume of Advances in Pharmacology explores the current concepts in drug metabolism and toxicology.
Author: Gabrielle M. Hawksworth
Publisher: Academic Press
This new volume of Advances in Pharmacology explores the current concepts in drug metabolism and toxicology. Chapters cover the Keap1-Nrf2 cell defense pathway, animal models of drug-induced idiosyncratic toxicity and the use of human embryonic and induced pluripotent stem cells for modeling metabolism and toxicity. With a variety of chapters and the best authors in the field, the volume is an essential resource for pharmacologists, immunologists and biochemists alike. Explores the current concepts in drug metabolism and toxicology Chapters cover such areas as the Keap1-Nrf2 cell defense pathway, animal models of drug-induced idiosyncratic toxicity and the use of human embryonic and induced pluripotent stem cells for modeling metabolism and toxicity An essential resource for pharmacologists, immunologists and biochemists alike
Likewise the contributors of this volume are leaders in their fields with worldwide expertise and perspective. Molecules, Systems and Signaling in Liver Injury is an essential companion to Hepatocytes and Non-Parenchymal Cells and Diseases.
Author: Wen-Xing Ding
This essential volume presents comprehensive information on cell death and autophagy in liver diseases, including the role and molecular signaling pathways of cell death in alcohol and non-alcoholic fatty liver disease, bile acids, hepatitis C virus and drug-induced liver injury. The book starts with a discussion of lipotoxicity in non-parenchymal cells, followed by a discussion of cell death and autophagy in cholangiocytes, hepatic stellate cells and Kupffer cells in hepatic biliary diseases, fibrosis and liver inflammation. The book also covers Bcl-2 family proteins, beta-catenin and HMGB1 signaling in regulating cell death in the liver as well as mitochondria, ER stress and gut microbiota on liver injury. The Cell Death in Biology and Diseases series has recruited world experts ranging from basic scientists to clinicians on cell death in liver diseases. Likewise the contributors of this volume are leaders in their fields with worldwide expertise and perspective. Molecules, Systems and Signaling in Liver Injury is an essential companion to Hepatocytes and Non-Parenchymal Cells and Diseases. It is beneficial for both clinicians and basic scientists and is relevant to those working on drug discovery for preventing and treating liver diseases by targeting cell death and autophagy pathways.
This outstanding new book elucidates new and important research results from throughout the world.
Author: T. M. Chen
Publisher: Nova Publishers
The liver is a large organ that sits in the right upper abdomen, just under the right lung. It is one of the body's most 'intelligent' organs in that it performs so many different functions at the same time. The liver makes proteins, eliminates waste material from the body, produces cholesterol, stores and releases glucose energy and metabolises many drugs used in medicine. It also produces bile that flows through bile ducts into the intestine where it helps to digest food. This organ also has the ability to regenerate itself if it is injured or partially removed. Cirrhosis is scarring of the liver that involves the formation of fibrous (scar) tissue associated with the destruction of the normal architecture of the organ. Many types of chronic injury to the liver can result in scar tissue. This scarring distorts the normal structure and re-growth of liver cells. The flow of blood through the liver from the intestine is blocked and the work done by the liver, such as processing drugs or producing proteins, is hindered. Until recently, the most common cause of cirrhosis of the liver in the United States was attributed to alcohol abuse. Because of the rapid increase of hepatitis C virus infection, hepatitis C has now taken over first place (26%), with alcohol abuse falling to second place, but only slightly behind at 21%. This outstanding new book elucidates new and important research results from throughout the world.
This book, therefore, will interest clinically oriented basic scientists as well as those in clinical practice, givng an update on many aspects of modern hepatology and its perspectives in the next millennium.
Author: J.L. Boyer
Publisher: Springer Science & Business Media
Liver cirrhosis is a major clinical problem worldwide and is associated with significant morbidity and mortality from its complications, such as liver cell insufficiency with coagulopathy and hepatic encephalopathy, portal hypertension with ascites and gastrointestinal bleeding, hepatorenal syndrome, HCC development and others. This volume, the proceedings of Falk Symposium 115 held in Basel, Switzerland, October 22-24, 1999 (Part II of the Basel Liver Week 1999; XI International Congress of Liver Diseases) covers our present knowledge of the aetiologies and early stages of liver cirrhosis development. Based on this information, strategies are discussed that are aimed at the prevention, early diagnosis and therapy of chronic liver diseases, thus preventing their progression to cirrhosis and its complications, including HCC development. The main topics mentioned above are complemented by three state-of-the-art chapters on modern aspects of medicine in general and hepatology in particular as well as their perspectives beyond the year 2000: `Molecular Medicine', `New Hepatitis Viruses' and `Genetic Liver Diseases: Diagnosis and Therapy'. Introductory chapters focusing on the more basic aspects of the biology of live cells as well as on the mechanisms underlying fibrogenesis, cholestasis and inflammation will be followed by a detailed discussion of the clinically most important causes of liver cirrhosis worldwide: hepatitis viruses B, C and D; toxins (alcohol, drugs and others) as well as metabolic liver diseases (haemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency, porphyria cutanea tarda and protoporphyria). This book, therefore, will interest clinically oriented basic scientists as well as those in clinical practice, givng an update on many aspects of modern hepatology and its perspectives in the next millennium.
Progress in Liver Diseases, Volume II presents the progress made in the understanding of bilirubin metabolism and secretion. This book discusses the mechanisms underlying the transport of bilirubin in the liver, intestine, and kidney.
Author: Hans Popper
Category: Health & Fitness
Progress in Liver Diseases, Volume II presents the progress made in the understanding of bilirubin metabolism and secretion. This book discusses the mechanisms underlying the transport of bilirubin in the liver, intestine, and kidney. Organized into 31 chapters, this volume begins with an overview of bilirubin metabolism and secretion from the point of view of transport within the liver cell. This text then discusses the relation of hematopoietic factors and coagulation mechanisms to hepatic function. Other chapters consider the etiology of viral hepatitis. This book discusses as well the appearance of genetic considerations in liver disease, as a reflection of progress in this discipline. The final chapter deals with the effects of closer relations with other nations and of migration from foreign lands and vice-versa, which have continued the interest in geographic pathology. This book is a valuable resource for pathologists, physicians, biochemists, physiologists, clinicians, and clinical researchers.
General anesthetic: Fluoroalkane, chloroform, enflurane, methoxyflurane, trichloro ethylene, fluroxene, divinyl ether, etc., can damage liver cells. 9. Other drugs: For example, a lot of traditional Chinese medicine compound ...
Author: Lanjuan Li
Publisher: Springer Nature
This book introduces the clinical application of artificial liver system (ALS) in hepatic failure. It has been widely used in clinics aiming to provide temporary support of liver function while maintaining extra-hepatic function in patients with liver failure. This work comprehensively summarizes the progress of livers and artificial liver, for example, the principle and implementation of Li-ALS, cell transplantation and the combined application of artificial liver and liver transplantation. It will be helpful for clinicians to implement artificial liver treatment to save the lives of patients with hepatic failure.
due to an increased turnover of liver cells. Chronic treatment with halothane produces during the first 4 weeks hypertrophy similar to that induced by barbiturates. In a later stage, after 2 and 6 months treatment, there is in addition ...
Author: H. Rašková
Mechanisms of Drug Toxicity, Volume 4 presents the proceedings of the 3rd International Pharmacological Meeting held in Sao Paulo, Brazil in 1966. The book discusses the drug-induced pathobiotic effects; the mechanisms of adverse reactions; and enzyme induction in the mechanism of chronic toxicity. The text also describes the influence of inducing substances on the growth of liver and microsomal electron transport systems; the quantitative aspects of chronic toxicity; and the facts and fallacies in predicting drug effects in human.