234 results match your criteria Halothane Hepatotoxicity

Fatal hepatotoxicity due to sevoflurane use in a paediatric patient after aortic repair: reality or fiction? A case of pharmacovigilance.

Eur J Hosp Pharm 2021 Apr 8. Epub 2021 Apr 8.

Cardiac Surgery Unit, Cardiac, Thoracic, Vascular and Public Health Science Department, Padova University Hospital, Padova, Italy.

Hepatotoxicity secondary to exposure of volatile anaesthetics is an exceptional finding, but its clinical interest depends on their frequent use, unpredictable appearance and potential severity. Halothane is the volatile anaesthetic most frequently involved in the development of liver dysfunction, especially after re-exposure. Sevoflurane has rarely been related to this life-threatening complication. Read More

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Fluorine-Containing Inhalation Anesthetics: Chemistry, Properties and Pharmacology.

Curr Med Chem 2020 ;27(33):5599-5652

School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, China.

Studies on fluorinated inhalation anesthetics, including synthesis, physical chemistry and pharmacology, have been summarized in this review. Retrospecting the history of inhalation anesthetics revealed their increasing reliance on fluorine and ether structures. Halothane causes a rare but severe immune-based hepatotoxicity, which was replaced by enflurane in the 1970s. Read More

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December 2020

Drug-induced liver injury in obesity and nonalcoholic fatty liver disease.

Adv Pharmacol 2019 20;85:75-107. Epub 2019 Feb 20.

INSERM, Univ. Rennes, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, Rennes, France. Electronic address:

Obesity is commonly associated with nonalcoholic fatty liver (NAFL), a benign condition characterized by hepatic lipid accumulation. However, NAFL can progress in some patients to nonalcoholic steatohepatitis (NASH) and then to severe liver lesions including extensive fibrosis, cirrhosis and hepatocellular carcinoma. The entire spectrum of these hepatic lesions is referred to as nonalcoholic fatty liver disease (NAFLD). Read More

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February 2020

Beyond Ether and Chloroform-A Major Breakthrough With Halothane.

J Anesth Hist 2017 Jul 3;3(3):87-102. Epub 2017 Jun 3.

University of Massachusetts School of Medicine, Worcester, MA. Electronic address:

Background: The use of equipment powered by electricity in the operating room increased the risk of fires in the presence of flammable agents such as ether and cyclopropane. Chloroform was associated with cardiac arrhythmias and liver damage. The introduction of halothane in the late 1950s was heralded as a solution to many problems facing the specialty of anesthesia. Read More

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Drug-Induced Liver Injury in Children: Clinical Observations, Animal Models, and Regulatory Status.

Int J Toxicol 2017 Sep/Oct;36(5):365-379. Epub 2017 Aug 18.

4 Gen-X-Tox, LLC, Sarasota, FL, USA.

Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. Read More

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Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity.

J Clin Transl Res 2017 Feb 12;3(Suppl 1):212-232. Epub 2017 Feb 12.

INSERM, U991, Université de Rennes 1, Rennes, France.

Background: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Read More

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February 2017

Contributions of caspase-8 and -9 to liver injury from CYP2E1-produced metabolites of halogenated hydrocarbons.

Xenobiotica 2018 Jan 12;48(1):60-72. Epub 2017 Jan 12.

a Cardiovascular Pharmacotherapy and Toxicology and.

1. Drug-induced liver injury is difficult to predict at the pre-clinical stage. This study aimed to clarify the roles of caspase-8 and -9 in CYP2E1 metabolite-induced liver injury in both rats and cell cultures in vitro treated with carbon tetrachloride (CCl), halothane or sevoflurane. Read More

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January 2018

Drug-induced allergic hepatitis develops in mice when myeloid-derived suppressor cells are depleted prior to halothane treatment.

Hepatology 2015 Aug 25;62(2):546-57. Epub 2015 Mar 25.

Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.

Unlabelled: Clinical evidence suggests that many cases of serious idiosyncratic drug-induced liver injury are mediated by the adaptive immune system in response to hepatic drug-protein adducts, also referred to as "drug-induced allergic hepatitis"; but detailed mechanistic proof has remained elusive due to the lack of animal models. We have hypothesized that drug-induced allergic hepatitis is as rare in animals as it is in humans due at least in part to the tolerogenic nature of the liver. We provide evidence that immune tolerance can be overcome in a murine model of halothane-induced liver injury initiated by trifluoroacetylated protein adducts of halothane formed in the liver. Read More

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Hepatotoxicity of halogenated inhalational anesthetics.

Iran Red Crescent Med J 2014 Sep 5;16(9):e20153. Epub 2014 Sep 5.

Department of Molecular Hepatology, Middle East Liver Disease Center, Tehran, IR Iran ; Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran.

Context: Halogenated inhalational anesthetics are currently the most common drugs used for the induction and maintenance of general anesthesia. Postoperative hepatic injury has been reported after exposure to these agents. Based on much evidence, mechanism of liver toxicity is more likely to be immunoallergic. Read More

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September 2014

Halothane-induced hepatitis: A forgotten issue in developing countries: Halothane-induced hepatitis.

Hepat Mon 2011 Jan;11(1):3-6

Department of Gastroenterology, Tehran University of Medical Sciences, Tehran, IR Iran.

Halothane was introduced as an anesthetic in the 1950s and was considered a revolutionary agent in the field of anesthesia. Soon after, halothane-induced hepatitis became a concern, leading to the development of less toxic gases that induced a lower incidence of side effects. Two types of halothane-related hepatotoxicity have been described: type 1, or mild hepatitis, is associated with elevated transaminase levels and self-limiting symptoms, and type 2, or severe hepatotoxicity, is associated with acute fatal liver failure and is fatal in most cases. Read More

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January 2011

Natural killer cells mediate severe liver injury in a murine model of halothane hepatitis.

Toxicol Sci 2011 Apr 18;120(2):507-18. Epub 2011 Jan 18.

Cell and Molecular Biology Program, Michigan State University, East Lansing, Michigan 48824-1302, USA.

Severe halothane (HAL)-induced hepatotoxicity occurs in one in 6000-30,000 patients by an unknown mechanism. Female sex is a risk factor in humans and rodents. We tested the hypothesis that a sex difference in natural killer (NK) cell activity contributes to HAL-induced liver injury. Read More

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A mouse model of severe halothane hepatitis based on human risk factors.

J Pharmacol Exp Ther 2010 May 2;333(2):364-72. Epub 2010 Feb 2.

Cellular and Molecular Biology Program, Michigan State University, East Lansing, Michigan 48824, USA.

Halothane (2-bromo-2-chloro-1,1,1-trifluoro-ethane) is an inhaled anesthetic that induces severe, idiosyncratic liver injury, i.e., "halothane hepatitis," in approximately 1 in 20,000 human patients. Read More

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Acute liver injury after sevoflurane anesthesia: A case report.

Korean J Anesthesiol 2009 Aug;57(2):221-224

Department of Anesthesiology and Pain Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Halothane, isoflurane and desflurane are metabolized to hepatotoxic trifluoroacetyl proteins. But sevoflurane is metabolized to hexafluoroisopropanol. Hexafluoroisopropanol has a low binding affinity for liver protein and is therefore rapidly converted to glucuronidate that are excreted in the urine. Read More

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Effect of polyI:C cotreatment on halothane-induced liver injury in mice.

Hepatology 2009 Jan;49(1):215-26

Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO, USA.

Unlabelled: Drug-induced liver injury (DILI) is a challenging problem in drug development and clinical practice. Patient susceptibility to DILI is multifactorial, making these reactions difficult to predict and prevent. Clinical observations have suggested that concurrent bacterial and viral infections represent an important risk factor in determining patient susceptibility to developing adverse drug reactions, although the underlying mechanism is not clear. Read More

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January 2009

The role of the antioxidants lycopene and vitamin E in the prevention of halothane-induced hepatotoxicity.

Methods Find Exp Clin Pharmacol 2008 Oct;30(8):627-31

Department of Anesthesiology and Reanimation, Firat University School of Medicine, Elazig, Turkey.

The aim of this study was to examine the effects of lycopene and vitamin E on halothane-induced hepatotoxicity. Thirty-five male albino Wistar rats were studied. The control group (group C) did not receive any treatment. Read More

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October 2008

Understanding the role of reactive metabolites in drug-induced hepatotoxicity: state of the science.

Expert Opin Drug Metab Toxicol 2008 Nov;4(11):1415-27

University of Liverpool, MRC Centre for Drug Safety Science, Department of Pharmacology & Therapeutics, L69 3GE, UK.

Drug-induced liver injury (DILI) represents a major impediment to the development of new drugs and is a leading cause of drug withdrawal. The occurrence of hepatotoxicity has been closely associated with the formation of chemically reactive metabolites. Huge investment has focused on the screening of chemically reactive metabolites to offer a pragmatic approach to produce safer drugs and also reduce drug attrition and prevent market place withdrawal. Read More

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November 2008

First use of halothane in the United States, C. Ronald Stephen, M.D. (1916-2006).

Bull Anesth Hist 2008 Jul-Aug;26(2):1, 4; discussion 5

University of Texas Southwestern Medical Center, USA.

Anesthesia is one of the most valued discoveries in all of history. Almost immediately after the first public demonstration of ether anesthesia, a search for a better drug began. Ether, despite its flammability, persisted as the primary inhalation agent for over a hundred years. Read More

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Protective role of zinc pretreatment in hepatotoxicity induced by halothane.

Eur J Anaesthesiol 2008 Oct 5;25(10):810-5. Epub 2008 Jun 5.

Selcuk University, Meram Medical Faculty, Department of Anesthesiology and Reanimation, Konya, Turkey.

Background And Objective: This study was designed to determine the protective effects of zinc on halothane induced hepatotoxicity.

Methods: Forty-five male Sprague-Dawley rats were divided into three groups. The halothane group received normal drinking water and diet; the zinc-halothane group received 227 mg L(-1) zinc sulphate in the drinking water and diet for 2 weeks; and the control group received normal diet and water. Read More

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October 2008

Toxicological significance of mechanism-based inactivation of cytochrome p450 enzymes by drugs.

Crit Rev Toxicol 2007 Jun;37(5):389-412

Laboratory of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Chosi, Japan.

Cytochrome P450 (P450) enzymes oxidize xenobiotics into chemically reactive metabolites or intermediates as well as into stable metabolites. If the reactivity of the product is very high, it binds to a catalytic site or sites of the enzyme itself and inactivates it. This phenomenon is referred to as mechanism-based inactivation. Read More

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Measuring covalent binding in hepatotoxicity.

Curr Protoc Toxicol 2007 May;Chapter 14:Unit14.6

Michigan State University, East Lansing, Michigan, USA.

Many hepatotoxicants like acetaminophen, chloroform, carbon tetrachloride, halothane, and thioacetamide cause hepatotoxicity through covalent binding of their reactive metabolites to proteins. The covalent binding to proteins may lead to dysfunction of critical proteins such as enzymes, transporters, receptors, and regulatory molecules. Because most reactive metabolites covalently bind to tissue macromolecules and tend to be unstable, they can not be isolated, and direct quantitation of the formation of reactive metabolites is not possible. Read More

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Role of neutrophils in a mouse model of halothane-induced liver injury.

Hepatology 2006 Dec;44(6):1421-31

Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

Drug-induced liver injury (DILI) is a major safety concern in drug development. Its prediction and prevention have been hindered by limited knowledge of the underlying mechanisms, in part the result of a lack of animal models. We developed a mouse model of halothane-induced liver injury and characterized the mechanisms accounting for tissue damage. Read More

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December 2006

Anaesthetic organ toxicity: is it really a problem?

Curr Opin Anaesthesiol 1998 Aug;11(4):399-401

Department of Anaesthesia, St Mary's Hospital, London W2 1NY, UK.

The hepatotoxicity of halothane is now well known, but only became apparent after several years of use. The nephrotoxicity of methoxyflurane was not realized immediately, but once identified, led to its withdrawal from use. Therefore, when new agents that appear to offer significant advantages over established drugs become available, exhaustive testing and monitoring is necessary to ensure their safety. Read More

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Role of animal models in the study of drug-induced hypersensitivity reactions.

Jack Uetrecht

AAPS J 2006 Jan 13;7(4):E914-21. Epub 2006 Jan 13.

Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.

Drug-induced hypersensitivity reactions (DHRs) are a major problem, in large part because of their unpredictable nature. If we understood the mechanisms of these reactions better, they might be predictable. Their unpredictable nature also makes mechanistic studies very difficult, especially prospective clinical studies. Read More

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January 2006

Fatal isoflurane hepatotoxicity without re-exposure.

Indian J Gastroenterol 2006 Jan-Feb;25(1):41-2

Department of General Surgery, Osmangazi University Faculty of Medicine, 26480 Eskisehir, Turkey.

Isoflurane is less hepatotoxic than its predecessors, halothane and enflurane. We present a 68-year-old man who developed fulminant and fatal hepatic necrosis two days after open cholecystectomy done under isoflurane anesthesia. Laboratory findings included grossly elevated transaminases and bilirubin and prolonged prothrombin time. Read More

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Inhaled anesthetic agents.

Joan Stachnik

Am J Health Syst Pharm 2006 Apr;63(7):623-34

Department of Pharmacy Practice, College of Pharmacy, University of Illinois Medical Center at Chicago, Chicago, IL, USA.

Purpose: The pharmacology, bioavailability and pharmacokinetics, indications, clinical efficacy, adverse effects and toxicities, and dosage and administration of the inhaled anesthetics are reviewed.

Summary: The inhaled anesthetics include desflurane, enflurane, halothane, isoflurane, and sevoflurane and are thought to enhance inhibitory postsynaptic channel activity and inhibit excitatory synaptic activity. The mechanism of action of inhaled anesthetics has not been completely defined. Read More

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Ca2+ cytochemical changes of hepatotoxicity caused by halothane and sevoflurane in enzyme-induced hypoxic rats.

World J Gastroenterol 2005 Aug;11(32):5025-8

Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200438, China.

Aim: To investigate the relation between hepatotoxicity of halothane and sevoflurane and altered hepatic calcium homeostasis in enzyme-induced hypoxic rats.

Methods: Forty-eight rats were pretreated with phenobarbital and randomly divided into six groups (eight in each group) and exposed to O(2)/ N(2)/1.2 MAC anesthetics for 1 h: normal control (NC), 21% O(2)/79% N(2); hypoxic control (HC), 14% O(2)/86%N(2); normal sevoflurane (NS), 21% O(2)/ N(2)/1. Read More

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In vivo interaction of pulmonary intravascular macrophages with activated platelets in microvessels of equine lung after multiple exposures to halothane, isoflurane, and thiamylal: a comparative ultrastructural and cytochemical study.

Anat Rec A Discov Mol Cell Evol Biol 2005 Jun;284(2):574-84

Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Ontario, Canada.

The pulmonary intravascular macrophages (PIMs) of equines contain a unique electron-dense surface coat that is predominantly composed of lipoproteins. A single exposure of inhalatory halothane causes mobilization of the surface coat into the endocytotic system of the PIMs, followed by expansion of the Golgi apparatus and its enrichment with acid phosphatase. Simultaneously, the cells of the lymphocytic series show hyperplasia in the form of mitotic changes inside the microvascular compartment of the lung. Read More

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