Drug-Induced Liver Injury
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.
Liver Diseases
Pathological processes of the LIVER.
Liver
Wounds and Injuries
Liver Cirrhosis
Liver Transplantation
The transference of a part of or an entire liver from one human or animal to another.
Liver Neoplasms
Tumors or cancer of the LIVER.
Brain Injuries
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.
Reperfusion Injury
Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.
Fatty Liver
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.
Liver Diseases, Alcoholic
Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.
Hepatocytes
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Liver Function Tests
Aspartate Aminotransferases
Spinal Cord Injuries
Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).
Microsomes, Liver
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
Drug-Induced Liver Injury, Chronic
Acetaminophen
Liver Failure, Acute
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
Kupffer Cells
Mitochondria, Liver
Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)
Injury Severity Score
An anatomic severity scale based on the Abbreviated Injury Scale (AIS) and developed specifically to score multiple traumatic injuries. It has been used as a predictor of mortality.
Disease Models, Animal
Hepatitis, Animal
INFLAMMATION of the LIVER in non-human animals.
Cholestasis
Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).
Hepatitis
INFLAMMATION of the LIVER.
Lung Injury
Damage to any compartment of the lung caused by physical, chemical, or biological agents which characteristically elicit inflammatory reaction. These inflammatory reactions can either be acute and dominated by NEUTROPHILS, or chronic and dominated by LYMPHOCYTES and MACROPHAGES.
Liver Circulation
The circulation of BLOOD through the LIVER.
Liver Cirrhosis, Experimental
Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.
Rats, Sprague-Dawley
Thioacetamide
Cytochrome P-450 CYP2E1
An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.
Acute Lung Injury
A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).
Eye Injuries
Rats, Wistar
Hepatectomy
Excision of all or part of the liver. (Dorland, 28th ed)
Necrosis
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
Neck Injuries
Protective Agents
Mice, Knockout
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Hepatic Stellate Cells
Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.
Hepatitis, Alcoholic
INFLAMMATION of the LIVER due to ALCOHOL ABUSE. It is characterized by NECROSIS of HEPATOCYTES, infiltration by NEUTROPHILS, and deposit of MALLORY BODIES. Depending on its severity, the inflammatory lesion may be reversible or progress to LIVER CIRRHOSIS.
Bile Ducts
The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.
Wounds, Nonpenetrating
Liver Neoplasms, Experimental
Experimentally induced tumors of the LIVER.
Acute Kidney Injury
1-Naphthylisothiocyanate
Liver Cirrhosis, Alcoholic
Fatty Liver, Alcoholic
Lipid infiltration of the hepatic parenchymal cells that is due to ALCOHOL ABUSE. The fatty changes in the alcoholic fatty liver may be reversible, depending on the amounts of TRIGLYCERIDES accumulated.
Analgesics, Non-Narcotic
Liver Extracts
Blast Injuries
Tumor Necrosis Factor-alpha
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Oxidative Stress
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Liver Abscess
Solitary or multiple collections of PUS within the liver as a result of infection by bacteria, protozoa, or other agents.
Abbreviated Injury Scale
Classification system for assessing impact injury severity developed and published by the American Association for Automotive Medicine. It is the system of choice for coding single injuries and is the foundation for methods assessing multiple injuries or for assessing cumulative effects of more than one injury. These include Maximum AIS (MAIS), Injury Severity Score (ISS), and Probability of Death Score (PODS).
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Lipopolysaccharides
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Glutathione
Alanine Transaminase
Lipid Peroxidation
Myocardial Reperfusion Injury
Transaminases
Back Injuries
Head Injuries, Closed
Traumatic injuries to the cranium where the integrity of the skull is not compromised and no bone fragments or other objects penetrate the skull and dura mater. This frequently results in mechanical injury being transmitted to intracranial structures which may produce traumatic brain injuries, hemorrhage, or cranial nerve injury. (From Rowland, Merritt's Textbook of Neurology, 9th ed, p417)
Soft Tissue Injuries
Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as "soft tissue injuries of the hand".
Diffuse Axonal Injury
Cholestasis, Intrahepatic
Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).
Craniocerebral Trauma
Immunohistochemistry
Cells, Cultured
Bilirubin
A bile pigment that is a degradation product of HEME.
Carcinoma, Hepatocellular
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
Carotid Artery Injuries
Damages to the CAROTID ARTERIES caused either by blunt force or penetrating trauma, such as CRANIOCEREBRAL TRAUMA; THORACIC INJURIES; and NECK INJURIES. Damaged carotid arteries can lead to CAROTID ARTERY THROMBOSIS; CAROTID-CAVERNOUS SINUS FISTULA; pseudoaneurysm formation; and INTERNAL CAROTID ARTERY DISSECTION. (From Am J Forensic Med Pathol 1997, 18:251; J Trauma 1994, 37:473)
Biological Markers
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Rats, Inbred Strains
Ethionine
2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms.
Gene Expression Regulation
Vascular System Injuries
Injuries to blood vessels caused by laceration, contusion, puncture, or crush and other types of injuries. Symptoms vary by site and mode of injuries and may include bleeding, bruising, swelling, pain, and numbness. It does not include injuries secondary to pathologic function or diseases such as ATHEROSCLEROSIS.
Choline Deficiency
A condition produced by a deficiency of CHOLINE in animals. Choline is known as a lipotropic agent because it has been shown to promote the transport of excess fat from the liver under certain conditions in laboratory animals. Combined deficiency of choline (included in the B vitamin complex) and all other methyl group donors causes liver cirrhosis in some animals. Unlike compounds normally considered as vitamins, choline does not serve as a cofactor in enzymatic reactions. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Dimethylnitrosamine
A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents.
Accidents, Traffic
Accidents on streets, roads, and highways involving drivers, passengers, pedestrians, or vehicles. Traffic accidents refer to AUTOMOBILES (passenger cars, buses, and trucks), BICYCLING, and MOTORCYCLES but not OFF-ROAD MOTOR VEHICLES; RAILROADS nor snowmobiles.
Dose-Response Relationship, Drug
Kidney
Burns
Trauma Severity Indices
Concanavalin A
A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Antioxidants
Liver Glycogen
Glycogen stored in the liver. (Dorland, 28th ed)
Liver, Artificial
Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.
Retrospective Studies
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Random Allocation
Mice, Transgenic
Cytokines
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Drugs, Chinese Herbal
Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.
Inflammation
Accidents, Occupational
Gene Expression
Reverse Transcriptase Polymerase Chain Reaction
L-Lactate Dehydrogenase
Peroxidase
Blotting, Western
Endotoxins
End Stage Liver Disease
Final stage of a liver disease when the liver failure is irreversible and LIVER TRANSPLANTATION is needed.
Treatment Outcome
Cytoprotection
Carbon Tetrachloride
Neutrophils
gamma-Glutamyltransferase
An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.
Cytochrome P-450 Enzyme System
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Interleukin-6
Plant Extracts
Glycochenodeoxycholic Acid
Hepatitis, Autoimmune
A chronic self-perpetuating hepatocellular INFLAMMATION of unknown cause, usually with HYPERGAMMAGLOBULINEMIA and serum AUTOANTIBODIES.
Risk Factors
Superoxide Dismutase
Needlestick Injuries
Ischemia
Whiplash Injuries
Glycyrrhizic Acid
A widely used anti-inflammatory agent isolated from the licorice root. It is metabolized to GLYCYRRHETINIC ACID, which inhibits 11-BETA-HYDROXYSTEROID DEHYDROGENASES and other enzymes involved in the metabolism of CORTICOSTEROIDS. Therefore, glycyrrhizic acid, which is the main and sweet component of licorice, has been investigated for its ability to cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure, as well as depression of the renin-angiotensin-aldosterone system.
Lung
Biliary Tract
The BILE DUCTS and the GALLBLADDER.
Bile Acids and Salts
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Bile
An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.
Jaundice
Smoke Inhalation Injury
Up-Regulation
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Models, Animal
Electric Injuries
Neutrophil Infiltration
The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.
Wounds, Gunshot
Nitric Oxide Synthase Type II
A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.
Hep G2 Cells
A human liver tumor cell line used to study a variety of liver-specific metabolic functions.
Lipid Metabolism
Tissue Distribution
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
Endotoxemia
A condition characterized by the presence of ENDOTOXINS in the blood. On lysis, the outer cell wall of gram-negative bacteria enters the systemic circulation and initiates a pathophysiologic cascade of pro-inflammatory mediators.
Prospective Studies
Propionibacterium acnes
Head Injuries, Penetrating
Head injuries which feature compromise of the skull and dura mater. These may result from gunshot wounds (WOUNDS, GUNSHOT), stab wounds (WOUNDS, STAB), and other forms of trauma.
Bromobenzenes
Caspase 3
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Phenobarbital
NF-kappa B
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Hepatomegaly
Enlargement of the liver.
Severity of Illness Index
Thiobarbituric Acid Reactive Substances
Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct.
Intestines
Recovery of Function
Shiitake Mushrooms
Keratin-18
In Situ Nick-End Labeling
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
Tooth Injuries
Cholestasis, Extrahepatic
Impairment of bile flow in the large BILE DUCTS by mechanical obstruction or stricture due to benign or malignant processes.
Alkaline Phosphatase
Injections, Intraperitoneal
Central Nervous System Depressants
Ischemic Preconditioning
A technique in which tissue is rendered resistant to the deleterious effects of prolonged ISCHEMIA and REPERFUSION by prior exposure to brief, repeated periods of vascular occlusion. (Am J Physiol 1995 May;268(5 Pt 2):H2063-7, Abstract)
Analysis of Variance
Rabbits
Inflammation Mediators
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.