Toxication
Toxication, toxification or toxicity exaltation is the conversion of a
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 conversion of a prodrug to a metabolite with desired pharmacological or toxicological activity. Codeine is an example of a prodrug, metabolized in the body to the active compounds morphine and codeine-6-glucuronide.
Toxication by enzymatic metabolism
CYP450 enzymes
Phase I of drug metabolism are bioactivation pathways, which are catalyzed by 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 and CYP3A are responsible for hepatotoxicity during drug metabolism with a number of different drugs, including flucloxacilin, trioleandomycin, and troglitazone.[3] Hepatotoxicity indicates the drug's toxicity to liver.
Other oxidoreductases
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.[5][6] 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.[5]
Other examples
Other examples of toxication by enzymatic metabolism include:
- Conversion of secondary amines in the stomach into carcinogenic nitrosamines via NO pathway.[7]
- Nicotine into the nitrosated carcinogenic NNK (4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone) in the lung.[8]
- 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
Arsenic contamination in drinking water can be chemically toxic. The uptake and metabolism of arsenic may result the damage to body. When organic arsenic is converted into more toxic inorganic arsenic, it causes carcinogenesis, cytotoxicity (toxic to cells) and genotoxicity (causing mutations in genes).[10]