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Carbon Tetrachloride: A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)Carbon Tetrachloride PoisoningLiver Cirrhosis, Experimental: Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.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.Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenicity.Hydrocarbons, HalogenatedCarbon: A nonmetallic element with atomic symbol C, atomic number 6, and atomic weight [12.0096; 12.0116]. It may occur as several different allotropes including DIAMOND; CHARCOAL; and GRAPHITE; and as SOOT from incompletely burned fuel.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Aspartate Aminotransferases: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2.Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals.Drug-Induced Liver Injury, Chronic: Liver disease lasting six months or more, caused by an adverse drug effect. The adverse effect may result from a direct toxic effect of a drug or metabolite, or an idiosyncratic response to a drug or metabolite.Hepatic Stellate Cells: Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Liver Diseases: Pathological processes of the LIVER.MalonatesPhosgene: A highly toxic gas that has been used as a chemical warfare agent. It is an insidious poison as it is not irritating immediately, even when fatal concentrations are inhaled. (From The Merck Index, 11th ed, p7304)Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent.Peroxides: A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)Carbon Monoxide: Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)Liver Regeneration: Repair or renewal of hepatic tissue.Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.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.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Dimethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents.Thioacetamide: A crystalline compound used as a laboratory reagent in place of HYDROGEN SULFIDE. It is a potent hepatocarcinogen.Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.Ethylene Dibromide: An effective soil fumigant, insecticide, and nematocide. In humans, it causes severe burning of skin and irritation of the eyes and respiratory tract. Prolonged inhalation may cause liver necrosis. It is also used in gasoline. Members of this group have caused liver and lung cancers in rodents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), 1,2-dibromoethane may reasonably be anticipated to be a carcinogen.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Fasciola hepatica: A species of helminth commonly called the sheep liver fluke. It occurs in the biliary passages, liver, and gallbladder during various stages of development. Snails and aquatic vegetation are the intermediate hosts. Occasionally seen in man, it is most common in sheep and cattle.Phenolphthaleins: A family of 3,3-bis(p-hydroxyphenyl)phthalides. They are used as CATHARTICS, indicators, and COLORING AGENTS.Trichloroethanes: Chlorinated ethanes which are used extensively as industrial solvents. They have been utilized in numerous home-use products including spot remover preparations and inhalant decongestant sprays. These compounds cause central nervous system and cardiovascular depression and are hepatotoxic. Include 1,1,1- and 1,1,2-isomers.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.1-Naphthylisothiocyanate: A tool for the study of liver damage which causes bile stasis and hyperbilirubinemia acutely and bile duct hyperplasia and biliary cirrhosis chronically, with changes in hepatocyte function. It may cause skin and kidney damage.EthaneLipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Viologens: A group of dipyridinium chloride derivatives that are used as oxidation-reduction indicators. The general formula is 1,1'-di-R-4,4'-bipyridinium chloride, where R = methyl, ethyl, benzyl or, betaine.Aspalathus: A plant genus of the family FABACEAE. It is the source of an herbal tea that is commonly consumed in South Africa. Members contain aspalathin and other polyphenols (PHENOLS).Trichloroethylene: A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment.Nanotubes, Carbon: Nanometer-sized tubes composed mainly of CARBON. Such nanotubes are used as probes for high-resolution structural and chemical imaging of biomolecules with ATOMIC FORCE MICROSCOPY.Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology.Eleusine: A plant genus of the family POACEAE. Finger millet or raggee (E. coracana) is an important food grain in southern Asia and parts of Africa.Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.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.Chlordecone: A highly chlorinated polycyclic hydrocarbon insecticide whose large number of chlorine atoms makes it resistant to degradation. It has been shown to be toxic to mammals and causes abnormal cellular changes in laboratory animals.Solvents: Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant & Hackh's Chemical Dictionary, 5th ed)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.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.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.Bromotrichloromethane: A potent liver poison. In rats, bromotrichloromethane produces about three times the degree of liver microsomal lipid peroxidation as does carbon tetrachloride.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.Liver Function Tests: Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions.Iridoids: A type of MONOTERPENES, derived from geraniol. They have the general form of cyclopentanopyran, but in some cases, one of the rings is broken as in the case of secoiridoid. They are different from the similarly named iridals (TRITERPENES).Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.Podophyllum: A genus of poisonous American herbs, family BERBERIDACEAE. The roots yield PODOPHYLLOTOXIN and other pharmacologically important agents. The plant was formerly used as a cholagogue and cathartic. It is different from the European mandrake, MANDRAGORA.Embelia: A plant genus of the family MYRSINACEAE. Members contain embelin.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Portal Pressure: The venous pressure measured in the PORTAL VEIN.Bromobenzenes: Derivatives of benzene in which one or more hydrogen atoms on the benzene ring are replaced by bromine atoms.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Cyclooctanes: A group of compounds with an 8-carbon ring. They may be saturated or unsaturated.Methyl Chloride: A hydrocarbon used as an industrial solvent. It has been used as an aerosal propellent, as a refrigerant and as a local anesthetic. (From Martindale, The Extra Pharmacopoeia, 31st ed, p1403)Malondialdehyde: The dialdehyde of malonic acid.Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights.Aldehydes: Organic compounds containing a carbonyl group in the form -CHO.Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.Iridoid Glycosides: A subclass of iridoid compounds that include a glycoside moiety, usually found at the C-1 position.Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.Lethal Dose 50: The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.Aspartate Aminotransferase, Mitochondrial: An aspartate aminotransferase found in MITOCHONDRIA.Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.Transforming Growth Factor beta1: A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.Diethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties.Silymarin: A mixture of flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum. It consists primarily of silybin and its isomers, silicristin and silidianin. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent.Rats, Inbred F344Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.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.Carbon Monoxide Poisoning: Toxic asphyxiation due to the displacement of oxygen from oxyhemoglobin by carbon monoxide.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).Transaminases: A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.GalactosamineGallic Acid: A colorless or slightly yellow crystalline compound obtained from nutgalls. It is used in photography, pharmaceuticals, and as an analytical reagent.Hydrocarbons, Chlorinated: Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.Arsenamide: Proposed chemotherapeutic agent against filaria and trichomonas.2-Acetylaminofluorene: A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines.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.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.Kupffer Cells: Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells.Plant Bark: The outer layer of the woody parts of plants.Salvia miltiorrhiza: A plant species which is known as an Oriental traditional medicinal plant.Ligation: Application of a ligature to tie a vessel or strangulate a part.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Aniline Hydroxylase: A drug-metabolizing, cytochrome P-450 enzyme which catalyzes the hydroxylation of aniline to hydroxyaniline in the presence of reduced flavoprotein and molecular oxygen. EC 1.14.14.-.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.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.Mice, Inbred C57BLAlkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.