Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. In humans and many other animals, they serve to break down alcohols that are otherwise toxic, and they also participate in the generation of useful aldehyde, ketone, or alcohol groups during the biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.
Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol. Disulfiram works by inhibiting the enzyme aldehyde dehydrogenase, causing many of the effects of a hangover to be felt immediately following alcohol consumption. Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, fast heart rate, low blood pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, abnormal heart rhythms, heart attack, acute congestive heart failure, unconsciousness, convulsions, and death.
Safrole is an organic compound with the formula CH2O2C6H3CH2CH=CH2. It is a colorless oily liquid, although impure samples can appear yellow. A member of the phenylpropanoid family of natural products, it is found in sassafras plants, among others. Small amounts are found in a wide variety of plants, where it functions as a natural antifeedant. Ocotea pretiosa, which grows in Brazil, and Sassafras albidum, which grows in eastern North America, are the main natural sources of safrole. It has a characteristic "sweet-shop" aroma.
Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is the object of pharmacokinetics. Metabolism is one of the stages of the drug's transit through the body that involves the breakdown of the drug so that it can be excreted by the body.
Tienilic acid or ticrynafen (USAN) is a loop diuretic drug with uric acid-lowering (uricosuric) action, formerly marketed for the treatment of hypertension. It was approved by FDA on May 2, 1979, and withdrawn in 1982, after case reports in the United States indicated a link between the use of ticrynafen and hepatitis.
Fomepizole, also known as 4-methylpyrazole, is a medication used to treat methanol and ethylene glycol poisoning. It may be used alone or together with hemodialysis. It is given by injection into a vein.
Iproniazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class. It is a xenobiotic that was originally designed to treat tuberculosis, but was later most prominently used as an antidepressant drug. However, it was withdrawn from the market because of its hepatotoxicity. The medical use of iproniazid was discontinued in most of the world in the 1960s, but remained in use in France until its discontinuation in 2015.
Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Their use dates back centuries and is intertwined with the discovery, understanding, and eventual recognition of their toxicity on humans and animals.
Ethylene glycol poisoning is poisoning caused by drinking ethylene glycol. Early symptoms include intoxication, vomiting and abdominal pain. Later symptoms may include a decreased level of consciousness, headache, and seizures. Long term outcomes may include kidney failure and brain damage. Toxicity and death may occur after drinking even in a small amount as ethylene glycol is more toxic than other diols.
Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 enzymes that metabolize polyunsaturated fatty acids (PUFAs) to epoxide products that have a range of biological activities.
Senecionine is a toxic pyrrolizidine alkaloid isolated from various botanical sources. It takes its name from the Senecio genus and is produced by many different plants in that genus, including Jacobaea vulgaris. It has also been isolated from several other plants, including Brachyglottis repanda, Emilia, Erechtites hieraciifolius, Petasites, Syneilesis, Crotalaria, Caltha leptosepala, and Castilleja.
Arsenic biochemistry refers to biochemical processes that can use arsenic or its compounds, such as arsenate. Arsenic is a moderately abundant element in Earth's crust, and although many arsenic compounds are often considered highly toxic to most life, a wide variety of organoarsenic compounds are produced biologically and various organic and inorganic arsenic compounds are metabolized by numerous organisms. This pattern is general for other related elements, including selenium, which can exhibit both beneficial and deleterious effects. Arsenic biochemistry has become topical since many toxic arsenic compounds are found in some aquifers, potentially affecting many millions of people via biochemical processes.
Toxicodynamics, termed pharmacodynamics in pharmacology, describes the dynamic interactions of a toxicant with a biological target and its biological effects. A biological target, also known as the site of action, can be binding proteins, ion channels, DNA, or a variety of other receptors. When a toxicant enters an organism, it can interact with these receptors and produce structural or functional alterations. The mechanism of action of the toxicant, as determined by a toxicant’s chemical properties, will determine what receptors are targeted and the overall toxic effect at the cellular level and organismal level.
Methanol toxicity is poisoning from methanol, characteristically via ingestion. Symptoms may include a decreased level of consciousness, poor or no coordination, vomiting, abdominal pain, and a specific smell on the breath. Decreased vision may start as early as twelve hours after exposure. Long-term outcomes may include blindness and kidney failure. Blindness may occur after drinking as little as 10 mL; death may occur after drinking quantities over 15 mL.
Glycidamide is an organic compound with the formula H2NC(O)C2H3O. It is a colorless oil. Structurally, it contains adjacent amides and epoxide functional groups. It is a bioactive, potentially toxic or even carcinogenic metabolite of acrylonitrile and acrylamide. It is a chiral molecule.
4-Ipomeanol (4-IPO) is a pulmonary pre-toxin isolated from sweet potatoes infected with the fungus Fusarium solani. One of the 4-IPO metabolites is toxic to the lungs, liver and kidney in humans and animals. This metabolite can covalently bind to proteins, thereby interfering with normal cell processes.
A disulfiram-like drug is a drug that causes an adverse reaction to alcohol leading to nausea, vomiting, flushing, dizziness, throbbing headache, chest and abdominal discomfort, and general hangover-like symptoms among others. These effects are caused by accumulation of acetaldehyde, a major but toxic metabolite of alcohol formed by the enzyme alcohol dehydrogenase. The reaction has been variously termed a disulfiram-like reaction, alcohol intolerance, and acetaldehyde syndrome.
2-Ethoxyethyl acetate is an organic compound with the formula CH3CH2OCH2CH2O2CCH3. It is the ester of ethoxyethanol and acetic acid. A colorless liquid, it is partially soluble in water.
