Definition
Description
Top Gene Interactions
Related Pathways
Nickel Health Effects
General Information
- 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 α2-macroglobulin. Nickel tends to accumulate in the lungs, thyroid, kidney, heart, and liver. Absorbed nickel is excreted in the urine, whereas unabsorbed nickel is excreted in the faeces. (L41)
- Uses/Sources: Pure nickel is mainly used to make alloys, which are found in items such as coins, jewelry, valves and heat exchangers. Nickel compounds are used for nickel plating, to color ceramics, to make some batteries, and as catalysts. (L41)
- Health Effects: 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. (L41)
- 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. (L42)
- 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. (L42)
- Route of Exposure: Oral (L41) ; inhalation (L41) ; dermal (L41)
Toxicity
- Carcinogenicity: Metallic nickel is possibly carcinogenic to humons (Group 2B). Nickel compounds are carcinogenic to humans (Group 1). (L135)
- Toxicity: LD50: 250 mg/kg (Intraperitoneal, Rat) (T26)
- Minimum Risk Level: Intermediate Inhalation: 0.0002 mg/m3 (L134) Chronic Inhalation: 0.00009 mg/m3 (L134)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2 |
Nickel substitutes for iron in alpha-ketoglutarate-dependent dioxygenases, inhibiting DNA repair. (A109) |
19096759 |
Egl nine homolog 2 Egl nine homolog 1 Egl nine homolog 3 |
Nickel substitutes for iron in hypoxia-inducible factor prolyl hydroxylases, inhibiting their enzyme activity. This results in the accumulation of hypoxia inducible factor 1 alpha, causing hypoxia-mimic stress. (A109) |
19096759 |
Calcineurin subunit B type 1 Calcineurin subunit B type 2 Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform |
Nickel is known to substitute for other essential elements in certain enzmes, such as calcineurin. (A40) |
6311199 |
Histone H4 Histone H3.1 Histone H3.1t Histone H3.3 Protamine-2 Protamine-3 Sperm protamine P1 Histone H1.1 Histone H1.2 Histone H1.3 Histone H1.4 Histone H1.5 Histone H1oo Histone H1t Histone H1x Testis-specific H1 histone Histone H2A type 1 Histone H2A type 1-A Histone H2A type 1-B/E Histone H2A type 1-C Histone H2A type 1-D Histone H2A type 1-H Histone H2A type 1-J Histone H2A type 2-A Histone H2A type 2-B Histone H2A type 2-C Histone H2A type 3 Histone H2A-Bbd type 1 Histone H2A-Bbd type 2/3 Histone H2A.J Histone H2A.V Histone H2A.x Histone H2A.Z Histone H2B type 1-A Histone H2B type 1-B Histone H2B type 1-C/E/F/G/I Histone H2B type 1-D Histone H2B type 1-H Histone H2B type 1-J Histone H2B type 1-K Histone H2B type 1-L Histone H2B type 1-M Histone H2B type 1-N Histone H2B type 1-O Histone H2B type 2-E Histone H2B type 2-F Histone H2B type 3-B Histone H2B type F-M Histone H2B type F-S Histone H2B type W-T Histone H3.3C Histone H3-like centromeric protein A Histone H4-like protein type G Putative histone H2B type 2-D Histone H3.2 Histone H1.0 |
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. (L41) |
2005 |
Lysine-specific demethylase 4A Lysine-specific demethylase 3A |
Nickel substitutes for iron in jmjC domain-containing histone demethylation proteins, inhibiting their demethylation activity. (A109) |
19096759 |