Nickel

Nickel/Drug Interactions:

  • AntidiabeticsAntidiabetics: According to secondary sources, the insulin response is increased after ingesting nickel, which may be related to its activation of enzymes associated with the breakdown or utilization of glucose.
  • AntineoplasticsAntineoplastics: According to review data, nickel has been shown to have carcinogenic effects (48; 49). The International Agency for Research on Cancer has classified nickel compounds as carcinogenic to humans. Of the trace elements, nickel is considered the most potent inducer of carcinogenesis in animal species and in in vitro mutagenic or chromosomal transformations (50). According to review and in vitro data, nickel activates apoptotic pathways, which may be the mechanism behind nickel-induced carcinogenesis (51; 52).
  • CYP450 substratesCYP450 substrates: According to in vitro research, nickel may regulate cytochrome P450-dependent microsomal drug-metabolizing enzymes by impairing cellular heme-dependent metabolism and by indirectly reducing the drug-detoxifying ability of cells; this effect may be additive with other metals (57).
  • Cytostatic agentsCytostatic agents: Nickel has been shown to enhance the cytotoxicity and genotoxicity of cis-platinum, trans-platinum, and mitomycin C (56). In vitro, significantly increased frequencies of rearranged chromosomes were detected in lymphocytes irradiated with gamma-rays that had been pretreated with low doses of mitomycin C and nickel, which did not cause chromosomal damage alone (369).
  • Disulfiram (Antabuse?)Disulfiram (Antabuse?): A metabolite of disulfiram chelates nickel, accelerating excretion of nickel in the urine (370). For this reason, it is used therapeutically in eczema patients with nickel hypersensitivity and also in the treatment of acute nickel carbonyl poisoning. However, disulfiram therapy has been associated with hepatotoxicity in women with nickel dermatitis (67; 68).
  • Gastrointestinal agentsGastrointestinal agents: According to secondary sources, acute nickel ingestion (325mg of nickel sulfate) has been shown to cause nausea, vomiting, and diarrhea. Accidental ingestion of 0.5-2.5g of nickel has been associated with nausea, vomiting, abdominal pain, and diarrhea, according to secondary sources.
  • Heart rate-regulating agentsHeart rate-regulating agents: According to secondary sources, acute nickel ingestion (325mg of nickel sulfate) has caused bradycardia. According to secondary sources, in a two year-old child, accidental ingestion of 10-15g of nickel sulfate caused tachycardia and cardiac arrest.
  • HepatotoxinsHepatotoxins: According to review data, nickel has been shown to have hepatotoxic effects (48).
  • Hormonal agentsHormonal agents: Nickel has been shown to cross the placenta and to have embryotoxic and teratogenic properties (59; 60). Nickel may upset the hormonal balance of the mother and may impair development of the preimplantation embryo (61).
  • ImmunostimulantsImmunostimulants: According to review data, nickel has been shown to have immunotoxic effects (48). In sensitive individuals, dermal or systemic exposure to nickel induces a type I immediate (anaphylactic) reaction and type IV delayed hypersensitivity reaction, mediated by secreted cytokines and allergen-specific T lymphocytes (54; 55). Patients with autoimmune thyroiditis and other autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, and atopic eczema) exhibited increased lymphocyte reactivity in vitro to nickel compared to healthy controls (53).
  • ImmunosuppressantsImmunosuppressants: According to review data, nickel has been shown to have immunotoxic effects (48). In sensitive individuals, dermal or systemic exposure to nickel induces a type I immediate (anaphylactic) reaction and type IV delayed hypersensitivity reaction, mediated by secreted cytokines and allergen-specific T lymphocytes (54; 55). Patients with autoimmune thyroiditis and other autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, and atopic eczema) exhibited increased lymphocyte reactivity in vitro to nickel compared to healthy controls (53).
  • NephrotoxinsNephrotoxins: According to review data, nickel has been shown to have nephrotoxic effects (48), especially in excessive amounts (10).
  • Neurologic agentsNeurologic agents: According to review data, nickel activates apoptotic pathways, which may be the mechanism behind nickel-induced neurotoxicity (51; 52). In PC12 cells, transcriptional profiling showed that nickel affected glutamate receptors to a greater extent than it affected genes related to oxidative stress (212). According to review data, acute nickel toxicity may cause cerebral edema that may lead to death (1).
  • RadiotherapyRadiotherapy: According to review data, nickel has been shown to enhance the cytotoxicity and genotoxicity of UV light and X-rays (56).
  • TobaccoTobacco: According to reviews, cigarettes may contain nickel and may increase nickel exposure (371; 372).
  • VasodilatorsVasodilators: According to secondary sources, nickel specifically affects the left coronary artery. Vasodilation and vasoconstriction occur with low and high levels of nickel, respectively.

    • Nickel/Herb/Supplement Interactions:

  • AntidiabeticsAntidiabetics: According to secondary sources, the insulin response is increased after ingesting nickel, which may be related to its activation of enzymes associated with the breakdown or utilization of glucose.
  • AntineoplasticsAntineoplastics: According to review data, nickel has been shown to have carcinogenic effects (48; 49). The International Agency for Research on Cancer has classified nickel compounds as carcinogenic to humans. Of the trace elements, nickel is considered the most potent inducer of carcinogenesis in animal species and in in vitro mutagenic or chromosomal transformations (50). According to review and in vitro data, nickel activates apoptotic pathways, which may be the mechanism behind nickel-induced carcinogenesis (51; 52).
  • CadmiumCadmium: Interactions of nickel with cadmium have been found to significantly reduce the experimental carcinogenicity of nickel and nickel compounds (30); further details are unavailable. It has been suggested that coexposure of cadmium with nickel may increase the risk of lung cancer (142). It is unclear if prostate cancer is associated with the manufacture of nickel-cadmium batteries (63; 64; 65; 66).
  • CalciumCalcium: According to review data, nickel may interfere with the metabolism of calcium, which may play a role in nickel-related carcinogenesis (11; 199).
  • CopperCopper: Interactions of nickel with copper have been found to significantly reduce the experimental carcinogenicity of nickel and nickel compounds (30).
  • CYP450 substratesCYP450 substrates: According to in vitro research, nickel may regulate cytochrome P450-dependent microsomal drug-metabolizing enzymes by impairing cellular heme-dependent metabolism and by indirectly reduce drug-detoxifying ability of cells; this effect may be additive with other metals (57).
  • Gastrointestinal agentsGastrointestinal agents: According to secondary sources, acute nickel ingestion (325mg of nickel sulfate) has been shown to cause nausea, vomiting, and diarrhea. Accidental ingestion of 0.5-2.5g of nickel has been associated with nausea, vomiting, abdominal pain, and diarrhea, according to secondary sources.
  • Heart rate-regulating agentsHeart rate-regulating agents: According to secondary sources, acute nickel ingestion (325mg of nickel sulfate) has caused bradycardia. According to secondary sources, in a two year-old child, accidental ingestion of 10-15g of nickel sulfate caused tachycardia and cardiac arrest.
  • Hepatotoxic agentsHepatotoxic agents: According to review data, nickel has been shown to have hepatotoxic effects (48).
  • Hormonal agentsHormonal agents: Nickel has been shown to cross the placenta and to have embryotoxic and teratogenic properties (59; 60). Nickel may upset the hormonal balance of the mother and may impair development of the preimplantation embryo (61).
  • ImmunostimulantsImmunostimulants: According to review data, nickel has been shown to have immunotoxic effects (48). In sensitive individuals, dermal or systemic exposure to nickel induces a type I immediate (anaphylactic) reaction and type IV delayed hypersensitivity reaction, mediated by secreted cytokines and allergen-specific T lymphocytes (54; 55). Patients with autoimmune thyroiditis and other autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, and atopic eczema) exhibited increased lymphocyte reactivity to nickel in vitro compared to healthy controls (53).
  • ImmunosuppressantsImmunosuppressants: According to review data, nickel has been shown to have immunotoxic effects (48). In sensitive individuals, dermal or systemic exposure to nickel induces a type I immediate (anaphylactic) reaction and type IV delayed hypersensitivity reaction, mediated by secreted cytokines and allergen-specific T lymphocytes (54; 55). Patients with autoimmune thyroiditis and other autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, and atopic eczema) exhibited increased lymphocyte reactivity to nickel in vitro compared to healthy controls (53).
  • IodineIodine: Interactions of nickel with iodine have been found to significantly reduce the experimental carcinogenicity of nickel and nickel compounds (30).
  • IronIron: According to review data, nickel may interfere with the metabolism of iron, influence iron absorption from foods, and play a role in production of red blood cells (11). It is unclear if iron inhibits or augments the carcinogenicity of nickel (373; 30). Iron deficiency anemia is often found in the presence of low nickel.
  • MagnesiumMagnesium: According to review data, nickel may interfere with the metabolism of magnesium (11; 374). According to review data, nickel-related carcinogenesis may be suppressed or modified by magnesium (204).
  • ManganeseManganese: According to review data, nickel may interfere with the metabolism of manganese (11). Interactions of nickel with manganese have been found to significantly reduce cytotoxicity and experimental carcinogenicity induced by nickel compounds (204; 30; 144; 375).
  • NephrotoxinsNephrotoxins: According to review data, nickel has been shown to have nephrotoxic effects (48), especially in excessive amounts (10).
  • Neurologic agentsNeurologic agents: According to review data, nickel activates apoptotic pathways, which may be the mechanism behind nickel-induced neurotoxicity (51; 52). In PC12 cells, transcriptional profiling showed that nickel affected glutamate receptors to a greater extent than it affected genes related to oxidative stress (212). According to review data, acute nickel toxicity may cause cerebral edema that may lead to death (1).
  • TobaccoTobacco: According to reviews, cigarettes may contain nickel and may increase nickel exposure (371; 372).
  • VasodilatorsVasodilators: According to secondary sources, nickel specifically affects the left coronary artery. Vasodilation and vasoconstriction occur with low and high levels of nickel, respectively.
  • Vitamin CVitamin C: It has been suggested that since nickel induces generation of reactive oxygen species and increased lipid peroxidation in various metabolically active tissues in humans and animals, vitamin C may serve as a protective antioxidant (220). According to secondary sources, vitamin C reduces intestinal nickel absorption.
  • Vitamin EVitamin E: Vitamin E may affect the genotoxicity and mutations induced by particulate and soluble nickel compounds; however, further information is lacking (193).
  • ZincZinc: According to review data, nickel may interfere with the metabolism of zinc (11; 15).

    • Nickel/Food Interactions:

  • GeneralGeneral: Certain food items, such as cocoa and chocolate, nuts, dried beans, peas, soya beans, spinach, lettuce, oatmeal, grains, fruits (including canned fruits), other vegetables (including canned vegetables) and leguminous seeds, as well as shellfish, salmon, hydrogenated shortenings, eggs, and milk may have very high nickel contents. Baking powder and cocoa powder may contain excessive amounts of nickel, due to nickel leaching during the manufacturing process (46). Consumption of these items in larger amounts may increase the nickel intake to 900mcg daily or more. Soft drinking water and acid beverages may dissolve nickel from pipes and containers. Leaching or corrosion processes may contribute significantly to the oral nickel intake, occasionally up to 1mg daily, which is equivalent to the tolerable upper intake level for nickel in adults.
  • PhytatesPhytates: Phytates are antioxidant compounds found in whole grains, legumes, nuts, and seeds. According to secondary sources, phytates may decrease nickel absorption.

    • Nickel/Lab Interactions:

  • Alanine aminotransferaseAlanine aminotransferase: According to review data, rats treated with nickel demonstrated reduced hepatic transaminase activity (220).
  • Aspartate aminotransferaseAspartate aminotransferase: According to review data, rats treated with nickel demonstrated reduced hepatic transaminase activity (220).
  • BilirubinBilirubin: According to review data, a transient increase in serum bilirubin occurred in workers who were hospitalized after drinking water from a nickel sulfate-contaminated water fountain (48).
  • Blood glucoseBlood glucose: According to secondary sources, the insulin response is increased after ingesting nickel, which may be related to its activation of enzymes associated with the breakdown or utilization of glucose.
  • Heart rateHeart rate: According to secondary sources, acute nickel ingestion (325mg of nickel sulfate) caused bradycardia. According to secondary sources, in a two year-old child, accidental ingestion of 10-15g of nickel sulfate caused tachycardia and cardiac arrest.
  • Immune panelImmune panel: According to review data, nickel has been shown to have immunotoxic effects (48). In sensitive individuals, dermal or systemic exposure to nickel induces a type I immediate (anaphylactic) reaction and type IV delayed hypersensitivity reaction, mediated by secreted cytokines and allergen-specific T lymphocytes (54; 55). Patients with autoimmune thyroiditis and other autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, and atopic eczema) exhibited increased lymphocyte reactivity to nickel in vitro compared to healthy controls (53).
  • Lipid profileLipid profile: According to review data, nickel sulfate may decrease cholesterol levels in rats (48).
  • RadiotherapyRadiotherapy: According to review data, nickel has been shown to enhance the cytotoxicity and genotoxicity of UV light and X-rays (56).