Nickel bis(dibutyldithiocarbamate) is an exogenous organic compound with the formula C18H36N2NiS4 and an average molecular weight of 467.44 g/mol. It exists as a solid at room temperature. Nickel bis(dibutyldithiocarbamate) belongs to the organic transition metal salts, a subclass of organic metal salts within the organic compounds. Industrially, the compound is used as an antioxidant. It has been recorded as being released from electrical and electronic equipment, specifically antennas, as well as building and construction materials, specifically ladders.
The compound interacts with several protein targets. Nickel substitutes for iron in alpha-ketoglutarate-dependent dioxygenases, including DNA oxidative demethylase ALKBH2 and alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3), which inhibits DNA repair. Similarly, it substitutes for iron in prolyl hydroxylases EGLN1, EGLN2, and EGLN3, inhibiting enzyme activity and causing hypoxia-mimic stress through the accumulation of hypoxia inducible factor 1 alpha. Nickel also substitutes for iron in jmjC domain-containing histone demethylation proteins, inhibiting their demethylation activity. Additionally, nickel is known to substitute for other essential elements in enzymes such as calcineurin, specifically targeting protein phosphatase 3 catalytic subunit alpha (PPP3CA) and calcineurin subunits B type 1 (PPP3R1) and type 2 (PPP3R2). Furthermore, nickel has a high affinity for chromatin proteins, including histone H1.4 (H1-4) and histone H2B type 1-C/E/F/G/I (H2BC4). The resulting complexing of nickel ions with heterochromatin can lead to gene silencing, DNA hypermethylation, condensation, and inhibition of histone acetylation, which disturb gene expression.
belongs to the class of organic compounds known as organic transition metal salts. These are organic salt compounds containing a transition metal atom in its ionic form.
Nickel is known to substitute for other essential elements in certain enzmes, such as calcineurin. It is genotoxic, and some nickel compounds have been shown to promote cell proliferation. Nickel has a high affinity for chromatin proteins, particularly histones and protamines. The complexing of nickel ions with heterochromatin results in a number of alterations including condensation, DNA hypermethylation, gene silencing, and inhibition of histone acetylation, which have been shown to disturb gene expression. Nickel has also been shown to alter several transcription factors, including hypoxia-inducible transcription factor, activating transcription factor, and NF-KB transcription factor. There is also evidence that nickel ions inhibit DNA repair, either by directly inhibiting DNA repair enzymes or competing with zinc ions for binding to zinc-finger DNA binding proteins, resulting in structural changes in DNA that prevent repair enzymes from binding. Nickel ions can also complex with a number of cellular ligands including amino acids, peptides, and proteins resulting in the generation of oxygen radicals, which induce base damage, DNA strand breaks, and DNA protein crosslinks. (3, 1)
Metabolism
Nickel is absorbed mainly through the lungs and gastrointestinal tract. Once in the body it enters the bloodstream, where it binds to albumin, L-histidine, and _2-macroglobulin. Nickel tends to accumulate in the lungs, thyroid, kidney, heart, and liver. Absorbed nickel is excreted in the urine, wherease unabsorbed nickel is excreted in the faeces. (3)
The most common harmful health effect of nickel in humans is an allergic reaction. This usually manifests as a skin rash, although some people experience asthma attacks. Long term inhahation of nickel causes chronic bronchitis and reduced lung function, as well as damage to the naval cavity. Ingestion of excess nickel results in damage to the stomach, blood, liver, kidneys, and immune system, as well as having adverse effects on reproduction and development. (3)
Symptoms
Symptoms of nickel poisoning include headache, nausea, vomiting, dizziness, irritability, and difficulty sleeping, followed by chest pains, sweating, rapid heart beat, and a dry cough. (4)
Treatment
Excess exposure to nickel is usually handled by preventing further exposure and symptomatic treatment. Nickel poisoning may also be treated using chelation therapy with sodium diethyldithiocarbamate. (4)
