# Toxication > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Toxication > Markdown URL: https://mediated.wiki/source/Toxication.md > Source: https://en.wikipedia.org/wiki/Toxication > Source revision: 1314603071 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{short description|Biological process of increasing toxicity}} '''Toxication''', '''toxification''' or '''toxicity exaltation''' is the conversion of a [chemical compound](/source/chemical_compound) into a more toxic form in living organisms or in substrates such as [soil](/source/soil) or [water](/source/water). The conversion can be caused by [enzymatic](/source/enzyme) [metabolism](/source/metabolism) in the organisms, as well as by [abiotic](/source/abiotic) [chemical reaction](/source/chemical_reaction)s. While the parent drug is usually less active, both the parent drug and its metabolite can be chemically active and cause [toxicity](/source/toxicity), leading to mutagenesis, teratogenesis, and carcinogenesis.{{Cite journal|title = The Role of Active Metabolites in Drug Toxicity|journal = Drug Safety|date = 2012-10-26|issn = 0114-5916|pages = 114–144|volume = 11|issue = 2|doi = 10.2165/00002018-199411020-00006|pmid = 7945999|language = en|first1 = Dr Munir|last1 = Pirmohamed|first2 = Neil R.|last2 = Kitteringham|first3 = B. Kevin|last3 = Park|s2cid = 24956095}}{{Cite journal|title = Overview of enzymes of drug metabolism|journal = Journal of Pharmacokinetics and Biopharmaceutics|date = 1996-10-01|issn = 0090-466X|pages = 449–459|volume = 24|issue = 5|doi = 10.1007/BF02353473|language = en|first = Urs A.|last = Meyer|pmid = 9131484|s2cid = 22586901}} Different classes of enzymes, such as [P450 monooxygenase](/source/P450_monooxygenase)s, [epoxide hydrolase](/source/epoxide_hydrolase), or [acetyltransferase](/source/acetyltransferase)s can catalyze the process in the cell, mostly in the liver. Parent non-toxic chemicals are generally referred to as ''protoxins''. While toxication is generally undesirable, in certain cases it is required for the ''[in vivo](/source/in_vivo)'' conversion of a [prodrug](/source/prodrug) to a metabolite with desired pharmacological or toxicological activity. [Codeine](/source/Codeine) is an example of a prodrug, metabolized in the body to the active compounds [morphine](/source/morphine) and [codeine-6-glucuronide](/source/codeine-6-glucuronide). == Toxication by enzymatic metabolism == === CYP450 enzymes === thumb|Enzyme CYP3A4, in CYP3A subfamily, contributes to hepatotoxicity during metabolism. Phase I of [drug metabolism](/source/drug_metabolism) are bioactivation pathways, which are catalyzed by [CYP450](/source/CYP450) enzymes, produce toxic metabolites and thus have the potential to damage cells. The unusual level of activity CYP450 enzymes might lead to the changes in drug metabolism and convert drugs into their more toxic forms. Among Phase I CYP450 enzymes, the subfamilies [CYP2D6](/source/CYP2D6) and [CYP3A](/source/CYP3A) are responsible for [hepatotoxicity](/source/hepatotoxicity) during drug metabolism with a number of different drugs, including [flucloxacillin](/source/flucloxacillin), [troleandomycin](/source/troleandomycin), and [troglitazone](/source/troglitazone).{{Cite journal|title = Drug-induced liver injury: insights from genetic studies|journal = Pharmacogenomics|pages = 1467–1487|volume = 10|issue = 9|doi = 10.2217/pgs.09.111|pmid = 19761370|first1 = Raúl J|last1 = Andrade|first2 = Mercedes|last2 = Robles|first3 = Eugenia|last3 = Ulzurrun|first4 = M Isabel|last4 = Lucena|year = 2009}} Hepatotoxicity indicates the drug's toxicity to liver. [Paracetamol](/source/Paracetamol) (acetaminophen, APAP) is converted into the hepatotoxic metabolite [NAPQI](/source/NAPQI) via the [cytochrome P450 oxidase](/source/cytochrome_P450_oxidase) system, mainly by the subfamily CYP2E1. Hepatic reduced glutathione (GSH) will detoxify this formed NAPQI quickly if APAP is taken at a proper level. In the case of overdoses, the storage of GSH will not be enough for NAPQI detoxication, thereby resulting in acute liver injury.{{Cite journal|title = Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease|journal = Liver International |date = 2014-08-01|issn = 1478-3231|pages = e171–e179|volume = 34|issue = 7|doi = 10.1111/liv.12514 |pmid = 24575957|language = en|first1 = Anaïs|last1 = Michaut|first2 = Caroline|last2 = Moreau|first3 = Marie-Anne|last3 = Robin|first4 = Bernard|last4 = Fromenty|doi-access = }} === Other oxidoreductases === [Oxidoreductases](/source/Oxidoreductases) are enzymes that catalyze the reactions that involve the transfer of electrons. [Methanol](/source/Methanol) in itself is toxic due to its [central nervous system depression](/source/central_nervous_system_depression) properties, but it can be converted to formaldehyde by alcohol dehydrogenase and then converted to formic acid by aldehyde dehydrogenase, which are significantly more toxic. [Formic acid](/source/Formic_acid) and [formaldehyde](/source/formaldehyde) can cause severe [acidosis](/source/acidosis), damage to the [optic nerve](/source/optic_nerve), and other life-threatening complications.{{Cite journal|title = Methanol and Ethylene Glycol Intoxication|journal = Critical Care Clinics|pages = 661–711|volume = 28|issue = 4|doi = 10.1016/j.ccc.2012.07.002|first = James A.|last = Kruse|pmid=22998995|year=2012}} centre|frameless|500x500px [Ethylene glycol](/source/Ethylene_glycol) (common antifreeze) can be converted into toxic [glycolic acid](/source/glycolic_acid), [glyoxylic acid](/source/glyoxylic_acid) and [oxalic acid](/source/oxalic_acid) by aldehyde dehydrogenase, lactate dehydrogenase (LDH) and glycolate oxidase in mammalian organisms.{{cite book|author1=Wayne Wingfield|author2=Marc Raffe|title=The Veterinary ICU Book|url=https://books.google.com/books?id=-DN35GUKOBgC&pg=PA1042|date=29 September 2002|publisher=Teton NewMedia|isbn=978-1-893441-13-2|pages=1042–}} The accumulation of the end product of the ethylene glycol mechanism, [calcium oxalate](/source/calcium_oxalate), may cause malfunction in the kidney and lead to more severe consequences. centre|frameless|800x800px === Other examples === Other examples of toxication by enzymatic metabolism include: * Conversion of [secondary amine](/source/secondary_amine)s in the stomach into carcinogenic [nitrosamine](/source/nitrosamine)s via NO pathway.{{Cite journal|title = Secondary Targets of Nitrite-Derived Reactive Nitrogen Species: Nitrosation/Nitration Pathways, Antioxidant Defense Mechanisms and Toxicological Implications|journal = Chemical Research in Toxicology|date = 2011-09-30|pages = 2071–2092|volume = 24|issue = 12|doi = 10.1021/tx2003118|pmid = 21923154|language = EN|first1 = Marco|last1 = d'Ischia|first2 = Alessandra|last2 = Napolitano|first3 = Paola|last3 = Manini|first4 = Lucia|last4 = Panzella}} * [Nicotine](/source/Nicotine) into the nitrosated carcinogenic [NNK](/source/NNK) (''4-(methylnitrosamino)- 1-(3-pyridyl)-1-[butanone](/source/butanone)'') in the lung.{{Cite journal|title = Formation and Analysis of Tobacco-SpecificN-Nitrosamines|journal = Critical Reviews in Toxicology|date = 1996-01-01|issn = 1040-8444|pages = 121–137|volume = 26|issue = 2|doi = 10.3109/10408449609017926|pmid = 8688156|first1 = Klaus D.|last1 = Brunnemann|first2 = Bogdan|last2 = Prokopczyk|first3 = Mirjana V.|last3 = Djordjevic|first4 = Dietrich|last4 = Hoffmann}} * [[Benzo(a)pyrene|Benzo[a]pyrene]] into the carcinogenic ''benzo[a]pyrene diol epoxide'' ([BP-7,8-dihydrodiol-9,10-epoxide](/source/BP-7%2C8-dihydrodiol-9%2C10-epoxide)) * [Hypoglycin A](/source/Hypoglycin_A) into the highly toxic [MCPA](/source/methylene_cyclopropyl_acetic_acid)-[CoA](/source/Coenzyme_A) == Toxication by abiotic chemical reactions == Increases in toxicity can also be caused by [abiotic](/source/abiotic) [chemical reactions.](/source/chemical_reaction) Non-living elements affect the abiotic chemical reactions. Anthropogenic trace compounds (ATCs) have potential toxicity to the organisms in aquatic system.{{Cite journal|title = Anthropogenic Trace Compounds (ATCs) in aquatic habitats — Research needs on sources, fate, detection and toxicity to ensure timely elimination strategies and risk management|journal = Environment International|date = 2015-06-01|pages = 85–105|volume = 79|doi = 10.1016/j.envint.2015.03.011|pmid = 25801101|first1 = Sabine U.|last1 = Gerbersdorf|first2 = Carla|last2 = Cimatoribus|first3 = Holger|last3 = Class|first4 = Karl-H.|last4 = Engesser|first5 = Steffen|last5 = Helbich|first6 = Henner|last6 = Hollert|first7 = Claudia|last7 = Lange|first8 = Martin|last8 = Kranert|first9 = Jörg|last9 = Metzger|doi-access = free}} [Arsenic](/source/Arsenic) contamination in drinking water can be chemically toxic. The uptake and metabolism of arsenic may result in damage to the body. When organic arsenic is converted into more toxic inorganic arsenic, it causes carcinogenesis, cytotoxicity (toxic to cells) and genotoxicity (causing mutations in genes).{{Cite journal |last1=Shankar |first1=Shiv |last2=Shanker |first2=Uma |last3=Shikha |date=2014-01-01|title=Arsenic contamination of groundwater: a review of sources, prevalence, health risks, and strategies for mitigation |journal=TheScientificWorldJournal |volume=2014 |article-number=304524 |doi=10.1155/2014/304524|issn=1537-744X|pmc=4211162|pmid=25374935|doi-access=free }} == See also == * [Chelation therapy](/source/Chelation_therapy) * [Detoxification](/source/Detoxification) == References == Category:Pharmacokinetics Category:Biodegradation --- Adapted from the Wikipedia article [Toxication](https://en.wikipedia.org/wiki/Toxication) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Toxication?action=history)). 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