Toxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as well as by abiotic chemical reactions. While the parent drug is usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis. Different classes of enzymes, such as P450 monooxygenases, epoxide hydrolase, or acetyltransferases can catalyze the process in the cell, mostly in the liver. Hepatotoxicity indicates the drug's toxicity to liver.
Paracetamol (acetaminophen, APAP) is converted into the hepatotoxic metabolite NAPQI via the 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.
Other oxidoreductases
Oxidoreductases are enzymes that catalyze the reactions that involve the transfer of electrons. Methanol in itself is toxic due to its 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 and formaldehyde can cause severe acidosis, damage to the optic nerve, and other life-threatening complications.
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Ethylene glycol (common antifreeze) can be converted into toxic glycolic acid, glyoxylic acid and oxalic acid by aldehyde dehydrogenase, lactate dehydrogenase (LDH) and glycolate oxidase in mammalian organisms. The accumulation of the end product of the ethylene glycol mechanism, calcium oxalate, may cause malfunction in the kidney and lead to more severe consequences.
- Nicotine into the nitrosated carcinogenic NNK (4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone) in the lung.
- [[Benzo(a)pyrene|Benzo[a]pyrene]] into the carcinogenic benzo[a]pyrene diol epoxide (BP-7,8-dihydrodiol-9,10-epoxide)
- Hypoglycin A into the highly toxic MCPA-CoA
Toxication by abiotic chemical reactions
Increases in toxicity can also be caused by abiotic chemical reactions. Non-living elements affect the abiotic chemical reactions. Anthropogenic trace compounds (ATCs) have potential toxicity to the organisms in aquatic system.
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).
See also
- Chelation therapy
- Detoxification