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( ref. see Hausinger )
The element nickel was discovered by Cronstedt in 1751. It was first purified as a metal by Berthier, ca. 1820. It is found as a red-coloured nickel-arsenide. The fume of this reddish substance is very toxic.
Gmelin (1826) gave rabbits and dogs high dosis of nickel-sulfate and observed symptoms of inflammation, generalized physical wasting, severe gastritis and fatal convulsations. The national research council (1975) summarized all the toxicity of nickel and nickel salts.
Herxheimer (1912) described a skin disease of workers in the nickel industry.
Doll (1958) could show in epidemiological studies that nickel can develop pulmonary and nasal cancers. These effects involve cellular changes on genetic level and are different from the general toxicity.
Betrand et al. (1967) showed growth stimulation by nickel in chlorella vulgaris.
Aggagg (1974) demonstrated the requirement of nickel for hydrogenase activity using the purified enzyme from nocardia opaca.
Dixon et al. showed that the jack bean urease contains nickel.
In the late 1800 there were reported some therapeutic uses of nickel compounds in humans (the effects are analgesic, sedative, anti-diarrheal and antiepileptic).
Mishra and Kar (1974) summarized the studies of the plant growth enhancement of low nickel concentrations. Most effects arise from this strong antifungal activity of nickel.
Environmental aspects of nickel
About 2 % of the earth mainly core and mantle regents contain about 2 % nickel.
The soils contain nickel at concentrations of 16 ppm (Nriagu 1980).
Nickel atom can bind 6-, 5-, 4-ligands.
Nickel (IV) or Nickel (III) are generally unstable, rapidly oxidies organic compounds while forming a nickel (II)species.
Nickel(III)species may play a biological role in genetic damage by nickel compounds and in certain nickel-containing enzymes. Nickel (II)- species represents the most common oxidation state of nickel and in environment we find many insoluble complexes of this state. (Nickel-sulfide, nickel-carbonate, nickel-oxide und nickel-phosphat). Soluble nickel complexes contain organic compounds like citrate, histidine and cystine.
The enzyme urease catalyzes the hydrolysis of urea to yield ammonia and carbamate , which spontaneously decomposes to form carbonic-acid and ammonia. There is evidence, that there are two nickel ions per catalytic unit. This demonstrate that nickel plays a more active chemical role than a structural one. Nickel containing ureases are found for example in helicobacter pylori, klebsiella aergenes, several lactobacilli-species, aspergillus nidulans and proteus mirabilis.
The hydrogenase activity catalyzes the reversible activation of hydrogen.
H2 < -‡ 2H(+) + 2e(-)
The hydrogenase catalyzed hydrogen production. It is observed in many fermentative reactions, including those of strict anaerobes such as clostridium spp.
Carbon monoxid dehydrogenase
carbon monoxid (CO) is metabolised by a wide range of microorganisms like aerobic bacteria including pseudomonas.
It is involved in biosynthesis or degradation of acetat.
CO + H2O ﬂ--> CO2 + 2H(+) + 2e(-)
CO plays a central role and the growth of acetogenetic and methano genetic bacteria.
Methyl Coenzyme M Reductase
The biogenesis of methane is carried out by strictly anaerobic bacteria.
Nickel transport into enteric bacteria.
Abelson et al. (1950) noticed that low magnesium concentrations lead to heightened toxicity of nickel and diminishes with increasing magnesium-ion concentrations.
Nelson indicated that magnesium-ion and cobalt-ion inhibit nickel uptake into E.coli.
Mechanism of nickel toxicity
The inhibition of essential enzymes and proteins by nickel-ion is the key side of toxicity of nickel.
Fuhrmann (1968) showed in a yeast-model, that nickel reduces the activity of alcohol-dehydroxygenase . The nickel-ion replaces the zink ion at the active catalytic side and blocks so the activity of alcohol dehydrogenase.
Nickel may replace other metal-ions in specific enzymes and so reduce the original activity or give reason for autoimmunity.
Nickel interferes with iron in redox-active ironproteins.
Nickel binds to RNA and DNA, glutathione acetyl-CoA and many other molecules. Many organic compounds can chelate nickel-ion and reduce its bioavailability and so reduce it´s toxicity. (Citrat, EDTA)
Alternatively, elevated concentrations of other metal-ions may increase the nickeltoxicity by substituting nickel ion, that otherwise would be sequestered into other organic compounds in the medium, thus increasing the concentration of free nickel ion.
As the ph decreases, protons compete more effectively with nickel ion for binding to the chelating components, the concentration of nickel ions increases and the nickel toxicity is elevated.
Nickeltolerance is often a plasmid-borne trait. It is associated with a energy-depending process of a extruding system of metals
Like zinc, cadmium, cobalt. Nies and Silver(1989 )
A single system for cobalt and nickel may be sufficient because both are chemically similar. There are other mechanisms of nickeltolerance identified yet.
uUtramafic and serpentine soils are very rich in nickel.
( Brooks,1987) There are found nickel-hyperaccumulating plants like Alyssum, Phyllanthus ,Thlaspi (Baker and Walker,1990)
Nickel is mainly sequestered into the leaves. There is a relation of nickel : cobalt = 7 : 1.
Animal nickel metabolism
A small portion of ingested nickel is absorbed in small intestine.
Non-absorbed nickel is eliminated into the feces while the absorbed portion is excreted by the kidney into the urinary tract. Nickel ion can be taken up into the cell by metal ion transport and lipophilic nickel complexes can defuse into the cell.
Nickelabsorption is not well understood but clearly biphasic. The first phase involves a saturable step associated with crossing the brush border membrane, whereas the second phase the uptake into the body is not saturable. (Foulkes and McMullen, 1986)
Low concentrations of nickel facilitate optimal growth of several animals.
Nickel is present in all animals, for example approximately 10 mg of nickel in the human body. In serum nickel binds to albumin and as well as to a large protein “nickeloplasmin” identified as alpha-2-macroglobulin. The alpha-2-macroglobulin is the major zink-binding protein in the serum. From serum nickel is rapidly distributed throughout the body.
It is highly distributed into the lunges, thyroid and adrenal. Nickel ion is rapidly excreted from the body through kidney and sweat.
Nickeldepletion in rats leads to increased mortality at birth, decreased weight, alterations of hair development and chicken to
pigmentation changes and swelling of the legs. ( Nielsen and Sauberlich, 1970, 1975 )
Immunological effects of nickel ( Type IV metalallergy )
Nickel leads to a allergic contact dermatitis, with a prevalence of 7 –10 % among women and 1-3 % among men ( menne´, 1992 )
The nickel contact dermatitis is a typical delayed-type hypersensitivity reaction to a nickel-conjugate antigen. ( rev. Nicklin and Nielsen, 1992 )
The Hypersensitivity response depend on the clonal T cells. It involves a cell-mediated immunereaction stimulated by an antigen, e. g. the HLA class II determinants and a antigenpresenting cell
( For example the langerhans cells of skin ) ( Sinigaglia et al, 1885 )
Severity of the dermatitis can be affected by nickel taken orally.
The asthmatic response type is antybody-mediated.
Nickel-albumin- or –proteinconjugate binds to nickel-specific IgE molecules, which bind to mastcells. ( Dolovich et al ,1984 )
This can lead to an acute bronchospasm and/or late response several hours later. ( Nicklin and Nielsen )
General toxicity of nickel
High Concentrations ( 2 – 5 mg/kg bodyweight ) can lead to a acute nephropathy. It result into a proteinuria and teturn to normal after some days. ( Gitlitz, 1975 )
Through free radical processes nickelsalts can exhibit toxic effects on liver.
Nickel salts can readily cross the placenta. ( Mas et al, 1985 )
There is evidence of Embryotoxicity in rodents.
Doll ( 1958 ) reported among 293 nickelworkers in south wales
Died 75 ( 25,6 % ) of lungcancer and 29 ( 9.9 % ) died of nasalcancer.
Sterzl found in patients with chronic fatigue a in vitro significant higher lymphocyt-stimulation of anorganic mercury and nickel compared with healthy contols.
Toxicol Appl Pharmacol. 1998 Jul;151(1):117-22.
Transport of nickel across monolayers of human intestinal Caco-2 cells.
Tallkvist J, Tjalve H.
Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, SE-751 23, Sweden.
The passage of nickel across monolayers of intestinal epithelial Caco-2 cells, originally derived from a human colonic adenocarcinoma, was studied in bicameral chambers. The results showed that the transport and accumulation of nickel were depressed in iron-loaded monolayers, indicating that the metal participates in an absorptive process for iron in the Caco-2 cells. No detectable transport of nickel in either the apical to basal or basal to apical direction occurred at 4 degreesC. Since cellular metabolism is inhibited at 4 degreesC, these data indicate that there is no passive transcellular or paracellular passage of the nickel across the monolayers. Studies in ATP-depleted monolayers showed an increased permeability of nickel, and concomitantly there was a similar increase in the permeability of the paracellular marker mannitol. These results indicate that the metabolic inhibition results in a loosening of the junctional complexes between the Caco-2 cells, resulting in a paracellular leakage of the nickel. Additional experiments showed that the transport of nickel in the basal to apical direction occurred at a higher rate than in the apical to basal direction. This indicates the presence of an extrusion mechanism that secretes the nickel from the basal to the apical side of the Caco-2 cells. Studies with Caco-2 cells and in vivo studies by other authors have shown similar results for other metals, indicating that colonic epithelial cells may have the ability to secrete some metals. Copyright 1998 Academic Press.