FACTOID # 21: 15% of Army recruits from South Dakota are Native American, which is roughly the same percentage for female Army recruits in the state.
 
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Encyclopedia > Hepatotoxins

Hepatotoxicity (from hepatic toxicity) is chemical-driven liver damage. Chemicals that cause liver damage are called hepatoxins. It is a possible side-effect of certain medications, but can also be caused by chemicals used in laboratories and industry, and natural chemicals, like microcystins. The liver is an organ in living beings, including humans. ... An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Chemical structure of Microcystin LR Microcystins are cyclic nonribosomal peptides produced by cyanobacteria. ...


Types

Hepatotoxicity can be considered to occur in two forms, symptomatic or idiosyncratic.


Drugs or toxins that have a symptomatic hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity. Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... A dose-response curve is a simple X-Y graph with Y usually being the measured dose (usually in milligrams, micrograms, or grams per kilogram of body-wieght) and X being the response. ...


In contrast, idiosyncratic hepatotoxins are agents that cause liver damage in only a small fraction of the population that is exposed to the agent, does not have a clear dose-response or temporal relationship, and most often do not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of several drugs from market even after rigorous clinical testing as part of the FDA approval process - Rezulin®(troglitazone), Ranitidine (Zantac®), and trovafloxacin (Trovan®) are three prime examples of idiosyncratic hepatotoxins. The development of ximelagatran (Exanta®) was discontinued for concerns of liver damage. Troglitazone (Rezulin®, Resulin® or Romozin®) is a member of the drug class of the thiazolidinediones. ... Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). ... Trovafloxacin (sold as Trovan by Pfizer) is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV [1]. It is not used widely due to the risk of hepatotoxicity. ... Ximelagatran (Exanta®, H 376/95) is an anticoagulant that has been investigated extensively but is awaiting approval by the Food and Drug Administration (FDA). ...


Acetaminophen and hepatotoxicity

One of the main causes of drug-induced hepatotoxicity in western countries is acetaminophen (paracetamol) poisoning, which is a symptomatic hepatotoxin. Hepatic damage can sometimes be detected at advanced stages by the typical yellow skin (jaundice) that arises from defective bilirubin liver metabolism. For earlier stages, there are a number of convenient liver function tests. Acetylcysteine can limit the severity of the liver damage by capturing the toxic acetaminophen metabolite. Acetaminophen (USAN) or paracetamol (INN), is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. ... Jaundice, also known as icterus (attributive adjective: icteric), is a yellowing of the skin, conjuctiva (clear covering over the sclera, or whites of the eyes) and mucous membranes caused by increased levels of bilirubin in the human body (or the body of another red blooded animal). ... Bilirubin is a yellow breakdown product of heme catabolism. ... It has been suggested that this article or section be merged with cell metabolism and carbohydrates. ... Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patients liver. ... N-acetylcysteine is a chemical, commonly called NAC, produced by the body that enhances the production of the molecule glutathione, a powerful antioxidant. ...


Hepatic metabolism

Many common drugs are metabolised by the liver in significant amounts. This, together with its role as first filter of blood loaded with substances absorbed from the gut, makes hepatotoxicity one of the main concerns of pharmaceutical companies in their research for new drugs. All lead optimisation cascades must deal in some way with the issue of hepatic toxicity. An especially thorny issue in drug discovery is enterohepatic circulation. Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... Human blood smear: a - erythrocytes; b - neutrophil; c - eosinophil; d - lymphocyte. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and... Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing, synthesizing and developing pharmaceutical drugs. ... In medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered and/or designed. ... Enterohepatic circulation, is the excretion of a drug (or a metabolite of it) through the bile to be re-absorbed in the gut and sent again to the liver along the portal vein, so the excretion-reabsortion cycle can start again. ...


  Results from FactBites:
 
Development of a DNA Microarray for Toxicology Based on Hepatotoxin-Regulated Sequences (6135 words)
A pool of liver RNA containing 10 mg from all rats treated with hepatotoxin was made and subtracted against a pool of liver RNA containing 150 mg from three naïve rats.
Toward this end, we dosed rats with 52 known hepatotoxins using a combination of drugs and chemicals that have been associated with different mechanisms of hepatotoxicity including DNA damage, oxidative stress, peroxisomal proliferation, necrosis, cirrhosis, steatosis, and protein synthesis inhibitors.
Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity.
Part II Herbs and Hepatic Toxicity (1406 words)
Some herbs are thought to be intrinsic hepatotoxins and show dose-related liver toxicity, either through direct hepatocellular damage, such as with Atractylis gummifera, or through the generation of a reactive metabolite, as is the case with pennyroyal oil (Mentha pulegium).[4]
In many instances, herbal hepatotoxins are thought to cause a hypersensitivity or idiosyncratic reaction.
The amount and duration of use of chaparral, the suspected hepatotoxin, was less than reported in previous cases.
  More results at FactBites »

 
 

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