Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Print this page Email this page Users Online: 257

 Table of Contents  
REVIEW ARTICLE
Year : 2015  |  Volume : 4  |  Issue : 2  |  Page : 75-85

A review on role of essential trace elements in health and disease


1 Intern, NRI Academy of Medical Sciences, Chinakakani, India
2 Department of Oral Pathology, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
3 Department of Oral Surgery, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India

Date of Web Publication12-Jun-2015

Correspondence Address:
Ravi Teja Chitturi
Department of Oral Pathology, Sibar Institute of Dental Sciences, Guntur - 522 509, Andhra Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-8632.158577

Rights and Permissions
  Abstract 

Elements are present in different forms in the nature, and these elements are very essential for the body to perform different functions. Trace elements are very important for cell functions at biological, chemical and molecular levels. These elements mediate vital biochemical reactions by acting as cofactors for many enzymes, as well as act as centers for stabilizing structures of enzymes and proteins. Some of the trace elements control important biological processes by binding to molecules on the receptor site of cell membrane or by alternating the structure of membrane to prevent entry of specific molecules into the cell. The functions of trace elements have a dual role. In normal levels, they are important for stabilization of the cellular structures, but in deficiency states may stimulate alternate pathways and cause diseases. These trace elements have clinical significance and these can be estimated using different analytical method.

Keywords: Analytical methods, body function, health, trace elements


How to cite this article:
Prashanth L, Kattapagari KK, Chitturi RT, Baddam VR, Prasad LK. A review on role of essential trace elements in health and disease. J NTR Univ Health Sci 2015;4:75-85

How to cite this URL:
Prashanth L, Kattapagari KK, Chitturi RT, Baddam VR, Prasad LK. A review on role of essential trace elements in health and disease. J NTR Univ Health Sci [serial online] 2015 [cited 2017 Oct 23];4:75-85. Available from: http://www.jdrntruhs.org/text.asp?2015/4/2/75/158577


  Introduction Top


We have less than 100 years of knowledge on role of elements in the human body. It is estimated that 98% of the body mass of man is made up of nine nonmetallic elements. [1] The four main electrolytes namely sodium, magnesium, potassium, and calcium constitute about 1.89%, while the rest 0.02% or 8.6 g of an average human adults is made up of 11 typical trace elements. [2] However, this tiny fraction exerts a tremendous influence on all body functions. Most of them mediate vital biochemical reactions by acting as a cofactor or catalyst for many enzymes. They also act as centers of building stabilizing structures such as enzymes and proteins. The accumulation of metals or deficiency of these elements may stimulate an alternate pathway which might produce diseases. Interaction among the trace elements may also act as a scaffold upon which the etiopathogenesis of many nutritional disorders lie. [3] Although these elements account for only 0.02% of the total body weight, they play significant roles, e.g., as active centers of enzymes or as trace bioactive substances. [4] Trace elements refers to "elements that occurs in natural and perturbed environments in small amounts and that, when present in sufficient bioavailable concentrations are toxic to living organism." [4]

Elements such as iron, zinc, and selenium are essential components of enzymes where they attract or subtract molecules and facilitate their conversion to specific end products. Few elements donate or accept electrons in redox reactions, which results in generation and utilization of metabolic energy and have an impact on the structural stability and to import certain biological molecules. Iron is involved in the binding, transporting, and release of oxygen in higher animals. Some of the trace elements control important biological processes by facilitating the binding of molecules to their receptor sites on cell membrane, by alternating the structures or ionic nature of membrane to prevent or allow specific molecules to enter or leave a cell and in inducing gene expression resulting in the formation of protein involved in life processes. [5]

Essential elements for human body

  • Four organic basic elements: H, C, N, O
  • Quantity elements - Na, Mg, K, Ca, P, S, Cl.
  • Essential trace elements - Mn, Fe, Co, Ni, Cu, Zn, Mo, Se, I.
  • Function suggested from active handling in humans, but no specific identified biochemical functions - Li, V, Cr, B, F, Si, As. [6]



  Biological Classification of Trace Elements Top


Various classifications have been proposed by so many authors on elements - both major as well as the trace elements, considered as essential for the normal development and growth.

Classification proposed by Frieden (1981) which divided the elements into micro, trace, and ultra-trace elements based on the amount found in tissues.

  1. Essential trace elements: Boron, cobalt, copper, iodine, iron, manganese, molybdenum, and zinc.
  2. Probable essential trace elements: Chromium, fluorine, nickel, selenium, and vanadium.
  3. Physically promotive trace elements: Bromine, lithium, silicon, tin, and titanium. [7]



  Categorical Classification of Trace Elements Top


It is observed that there are at least 29 different types of elements including metal and nonmetals in an adult human body. These 29 elements can be broadly classified into five major groups they are as follows:

  1. Group I: These elements are the basic components of macromolecules such as carbohydrates, proteins, and lipids. The elements belonging to these groups are carbon, hydrogen, oxygen, and nitrogen.
  2. Group II: These are nutritionally important minerals. They are also called as principal elements or macro elements. Their daily requirement for an adult human is above 100 mg/day. The deficiency of such elements usually proves fatal unless intervened properly. The elements belonging to this group are sodium, potassium, chloride, calcium, phosphorous, magnesium, sulfur.
  3. Group III: There are the essential trace elements. An element is called as trace elements when their requirement per day is below 100 mg and deficiency leads to disorders and may prove fatal. The elements belonging to this group are copper, iron, zinc, chromium, cobalt, iodine, molybdenum, and selenium. Of these, iodine is a nonmetal, while others are metals.
  4. Group IV: They are additional trace elements. Their role is not clear and they may be essential. The elements belonging to this group are cadmium, nickel, silica, tin, vanadium, and aluminum.
  5. Group V: This group of metals is not essential their presence may produce toxicity. They have no known function in the human body. The elements belonging to this group are gold, mercury, cyanide, and lead. [8]


The trace elements included Group III also called as minor elements. Their requirement is below 100 mg/day and their absence may not hinder normal development, but their activity may be substituted by another metal. [8] Analytical methods are used to measure metal concentration in human tissues and body fluids. [9]

Essential trace elements

The essential trace elements are broadly categorized into macro elements and trace or microelements [Table 1] and [Table 2]. [7]
Table 1: Macro Elements


Click here to view
Table 2: Trace or Micro Elements

Click here to view


The trace elements in human enzyme system

Copper (Cu)

Copper plays a very important role in our metabolism largely because it allows many critical enzymes to function properly. [10] Acidic conditions promotes the solubility which incorporates copper ions either in cupric form or cuprous form into the food chain. Copper toxicosis in plants is very rare compared to its deficiency while in animals and man toxicosis is usually induced by environmental concentrations in genetically abnormal individual. [11] Mainly copper is available in the liver, shellfish, dried fruit, milk and milk products, sunflower seeds, oysters, sesame seeds, tahini, and sun dried tomatoes. [12] The average content of metal in the plant usually ranges from 4 to 20 mg of copper per kg of dry weight. The average adult human of 70 kg weight contains about 100 mg. The daily requirement is about 2-5 mg of which 50% is absorbed from the gastrointestinal tract (GIT). Rest is excreted via bile and kidney. Copper accumulates in the liver, brain and kidney more than rest of body. Over 90% of plasma copper is associated with ceruloplasmin and 60% of red blood cell (RBC) is bound to superoxide dismutase. [13]

In human blood, copper is principally distributed between the erythrocytes and in the plasma. In erythrocytes, 60% of copper occurs as the copper-zinc metalloenzyme superoxide dismutase, the remaining 40% is loosely bound to other proteins and amino acids. Total erythrocytes copper in normal human is around 0.9-1.0 pg/ml of packed red cells. [14] Copper has a selected biochemical function in hemoglobin (Hb) synthesis, connective tissue metabolism, and bone development. Synthesis of tryptophan is done in the presence of Cu. Besides these Cu as ceruloplasmin aid in the transport of iron to cells. [15] A deficiency of Cu in diet for prolonged period especially during stages of active growth leads to anemia, growth retardation, defective keratinization and pigmentation of hair, hypothermia, mental retardation, changes in skeletal system, and degenerative changes in aortic elastin. [16] Excessive Cu either from diet or through any other sources acquired rapidly produces nausea, vomiting, diarrhea, profuse sweating, and renal dysfunction. When the levels of Cu are acquired very slowly, they cause cirrhosis, hepatitis, tremors, mental detritions,  Kayser-Fleischer ring More Detailss, hemolytic anemia, GIT bleeding and azotemia. [16] Congenital diseases like Wilson's disease, Menke's syndrome, idiopathic fibrosis of lung has been associated with Cu. Vineyard sprayer's lung diseases is an occupational hazard due to Cu intake via aerosol which 75% is in blood. [17]

The serum levels of copper increases in patients with myocardial infarction, leukemia, solid tumors, infections, cirrhosis of liver, hemochromatosis, thyrotoxicosis, and computed tomography disorders. Decreased levels occur in nephrotic syndrome, Kwashiorkor, Wilson's disease, severe diarrhea, and vomiting. [18] The symptoms of copper deficiency are hypochromic anemia, neutropenia, hypopigmentation of hair and skin, abnormal bone formation with skeletal fragility and osteoporosis, joint pain, lowered immunity, vascular abnormalities, and uncrimped or steely hair. [19] High copper intake for prolonged period causes increased copper percentages in serum and tissue that in turn causes oxidative stress and affects several immune functions. [18] Decreased copper levels are observed in few malignancies, mostly in the tumors which have high catabolic rate or which is of highly metastatic type. Some of the trace elements like copper and zinc have an anticarcinogenic role. Copper is involved in the cell metabolism, and is a part of various enzymes such as tyrosinase, uricase, and cytochrome oxidase, which are mainly concerned with oxidation reaction. The mean serum copper levels were significantly higher in the sera of patients with oral potentially malignant disorders such as oral leukoplakia and oral submucous fibrosis and also malignant tumors such as squamous cell carcinoma. In oral submucous fibrosis patients, the serum levels of Cu gradually increases as the clinical stage of the disease progresses. [20]

Iron (Fe)

Iron is present in huge quantities all over the earth crust and also is available to a great extent from the plant kingdom. Acidic condition promotes the solubility of iron as ions either in ferric or ferrous forms. The total body content of iron is about 3-5 g of which 75% is in blood while the rest is in liver, bone marrow and muscles. [21] Heme is the major iron containing substance. It is found in Hb, myoglobin, cytochrome while the enzymes associated with iron are cytochrome A, B, C, F 450, cytochrome C reductase, catalases, peroxidases, xanthine oxidases, tryptophan pyrrolase, succinate dehydrogenase, glucose 6 phosphate dehydrogenase, and choline dehydrogenase. [21]

An average daily requirement is 1-2 mg which has to provide as 20 mg of iron in food. Phytates and oxalates reduce the iron absorption in the GIT. Iron is absorbed from food when there is a need and the transport form of iron is known as ferritin. Hemosiderin is a golden brown pigment seen in cells of the reticuloendothelial system which is denatured form of ferritin. [2] The metabolism of iron is unique because it maintains homeostasis by regulating the absorption of iron but not excretion. When iron stores in the body are depleted, absorption is enhanced. [21] Deficiency of such an important trace metal will cause severe disorders, most important among them is iron deficiency anemia. [22] Microcytic hypochromic RBC's, tiredness, achlorhydria,  Plummer-Vinson syndrome More Details, atrophy of epithelium, impaired attention, irritability, and lowered memory are some of the features of iron deficiency anemia. [22] Iron deficiency anemia can lead to heart failure. [23] Anemia is the second most important cause of maternal mortality in India and it is estimated that about 20% of maternal deaths are directly related to anemia and another 50% of maternal deaths are associated with it. [24]

The deficiency when prolonged will be fatal. When iron is increased in body acutely, nausea, vomiting, diarrhea occurs along with hepatic damage. While chronic or prolonged accumulation of iron in body occurs there is a hepatic failure, diabetes, testicular atrophy, arthritis, cardiomyopathy, peripheral neuropathy, and hyperpigmentation. [25] Bronze diabetes is a triad of hemochromatosis, diabetes, and cirrhosis. The hepatic peptide hepcidin is an important systemic iron regulatory hormone. It regulates intestinal iron absorption, plasma iron concentrations, and tissue iron distribution by inducing degradation of its receptor and the cellular iron exporter ferroportin. Ferroportin exports iron into plasma from absorptive enterocytes, from macrophages that recycle the iron from senescent erythrocytes, and from hepatocytes that store iron. Deficiency of hepcidin causes hemochromatosis. [26] There are very few genetic disorders related to iron. One of them is due to an abnormal gene located on short arm of chromosome number 6 and linked to human leukocyte antigen - A locus. [27] The erythropoietin may be inhibited by cytokines such as interleukin 1, 6, tumor necrosis factor α, and interference. Serum ferritin levels are elevated, serum iron concentrations are decreased with tumor progression in head and neck carcinomas and thus it can be used as a follow-up tool for patients.[28] There are studies related to potentially malignant disorders and iron. In oral submucous fibrosis and oral leukoplakia, there is a significant decrease in Hb and serum iron, whereas in oral submucous fibrosis the total iron binding capacity showed statistically significant changes. [29] Recently, it has been found that iron may play a role in esophageal carcinogenesis. [30]

Zinc (Zn)

The metal zinc is an omnipotent metal that has amphoteric nature. Hence, it is ionized either in acidic or alkaline forms. Content of zinc is 2-3 ng the average body content of zinc is 2-3 g in an average adult. [31] About 99% is intracellular while the rest is in plasma. The average daily requirement is 15-20 mg/day. Phytase decreases fibers, phosphates, calcium, and copper competes with zinc for absorption from small intestine. [32] About 2-5 mg/day is excreted via pancreas and intestine. The other mode of excretion is via proximal tubule and sweat glands. [33]

Plasma zinc levels are decreased in pregnancy, fluid loss, oral contraceptive usage, blood loss, acute myocardial infarction, infections, and malignancies. [34] The function of zinc in cells and tissues is dependent on metalloproteinase and these enzymes are associated with reproductive, neurological, immune, dermatological systems, and GIT. It is essential for normal spermatogenesis and maturation, genomic integrity of sperm, for normal organogenesis, proper functioning of neurotransmitters, proper development of thymus, proper epithelialization in wound healing, taste sensation, and secretion of pancreas and gastric enzymes. [35] They can be biochemically classified as those involved in nucleic acid and protein synthesis and degradation, alcohol metabolism, carbohydrate, lipid, and protein metabolism. [31] They include transferases, hydrases, lyses, isomerizes oxidoreductases, and transcription factors. The enzyme most essential for zinc are alkaline phosphates, alcohol dehydrogenase, carboanhydrase, glutamate and lactase dehydrogenase, and RNA polymerases. The deficiency symptoms include compromised energy metabolism, alcohol intoxication, acidosis, blockage of protein biosynthesis, transmutation reaction blocked cell destruction by superoxide radicals. [31] Zinc plays an important role in cell proliferation, differentiation and metabolic activity of the cell. These modifications will take place in the presence of many zinc-binding proteins. Intracellular zinc is homeostatically maintained at extremely low levels either by sequestration in intracellular vesicles or binding to intracellular metalloproteinase and low molecular weight ligands. [36] Their reaction causes growth retardation, alopecia, dermatitis, immunological dysfunction, psychological disturbances, gonadal atrophy, faulty spermatogenesis, congenital malformation, keratogenesis, taste disorders, and delayed wound healing. The genetic disorder related with zinc metabolism is acrodermatitis enteropathica which is an autosomal recessive defect where there is an inability in Zn absorption. [37] Zinc also supports normal growth and development during pregnancy, childhood, and adolescence. [38] Zinc plays an important role in the proliferation, differentiation, and metabolic function of mammalian cells. Various extracellular signals, e.g., redox stress, cytokines, and growth factors stimulate the release of zinc from metallothionein or alter the transport of zinc which alters the intracellular level of mobile reactive zinc. Zinc then binds to and activates metal responsive transcription factors or interacts directly with intracellular signaling molecules to modulate the expression of zinc-responsive genes and to regulate specific signal transduction pathways. Mutations that activate H-Ras are oncogenic in most cells and lead to malignant transformation and this Ras signaling pathway is inhibited by zinc. [36]

Chromium (Cr)

Chromium word is derived from Greek in which chrome means "color". First identified as PbCro4. Full name of chromium is chromium acetylacetonate. [39] The total content of chromium is about 0.006 g in an average human adult. The daily requirement is about 0.005 mg/day. The need of chromium is for biosynthesis of glucose tolerance factor. The deficiency causes impairment of glucose tolerance while toxicity results in renal failure, dermatitis, and pulmonary cancer. [40] Processed meats, whole grain products, pulses, and spices are the best sources of chromium, while dairy products and most fruits and vegetables contain only small amounts. [41] Chromium content in animal foodstuff such as meat, poultry, and fish is low which provides 2 μg Cr. Most dairy products are also low in Cr and provide <0.6 μg/serving. Whole wheat and wheat flour contain 5-10 μg of Cr/kg. Pulses, seeds, and dark chocolate may contain more chromium than most other foods. Certain spices such as black pepper contain high concentrations of chromium. Chromium is excreted principally in the urine and in small quantities in the hair, sweat, and bile. The major route of elimination after absorption is fecal. [42] Chromium is a human carcinogen primarily by inhalation exposure in occupational settings. Lung cancer has been established as a consequence of hexavalent chromium exposure in smokers and nonsmokers and some cancers of other tissues such as GIT and central nervous system. The most recent data reveals the induction of skin tumors in mice by chronic drinking-water exposure to hexavalent chromium in combination with solar ultraviolet light. [43],[44] Chromium deficiency is difficult to document because of the very low levels present in blood, while tissue levels are 10 times higher. If concentrations of chromium are lower than the normal value of 0.14-0.15 ng/ml for serum or 0.26 or 0.28 ng/ml for plasma it indicates the presence of a severe chromium deficiency. Raised plasma levels can coexist with a negative balance. Hyperglycemia may be associated with raised plasma chromium and increased urinary excretion, without reflecting tissue level. Chromium concentrations in urine, hair, and other tissues or body fluids have also been reported not to reflect chromium status. The role of chromium supplementation was investigated in special subgroups of patients with diabetes. [45] Longstanding exposure with chromium will cause chronic ulcers of the skin and acute irritative dermatitis have been consistently reported in workers exposed to chromium containing materials. [46] Inhalation of Chromium compounds causes marked irritation of the respiratory tract. Rhinitis, bronchospasm, and pneumonia. [45] Chromium is considered to be a one of the risk factor for oral squamous cell carcinoma. Welding fumes involves exposure to many chemicals, including metal dust, irritant gases. Welding in stainless steel is associated with an increased risk of cancer of larynx and pharynx due to exposure to hexavalent chromium. [46]

Cobalt

The average human adult contain about 1.1 g with the daily requirement of 0.0001 mg/day. It is a component of Vitamin B12. It induces erythropoietin and blocks iodine uptake by the thyroid. It has a role to play in methionine metabolism where it controls the transfer of enzymes like homocysteine methyltransferase. Deficiency produces cardiomyopathy, congestive cardiac failure, pericardial effusion, polycythemia, and thyroid enlargement. [47] The occurrence of cobalt in animal tissues was demonstrated by Bertrand and Macheboeuf in 1925 and a wide distribution was confirmed by other workers employing spectrographic methods. [48] Cobalt is usually found in the environment combined with other elements such as oxygen, sulfur, and arsenic. Small amounts of these chemical compounds can be found in rocks, soil, plants, and animals. Most of the production of cobalt involves the metallic form used in the formation of cobalt super alloys. The term "hard metal" refers to compounds containing tungsten carbide (80-95%) combined with matrices formed from cobalt (5-20%) and nickel (0-5%). For the general population, the diet is the main source of exposure to cobalt. Meat, liver, kidney, clams, oysters, and milk all contain some cobalt. Ocean fish and sea vegetables have cobalt, but land vegetables have very little; some cobalt is available in legumes, spinach, cabbage, lettuce, beet greens, and figs. [47] The recommended daily intake of Vitamin B12 for an adult in the USA was said to be 3 μg, corresponding to 0.012 μg of cobalt. [45] Cobalt compounds are absorbed by the oral and inhalation routes and through the skin. The degree of gastrointestinal absorption depends on the dose; very small doses in the order of a few μg/kg are absorbed almost completely, whereas larger doses are less well absorbed. [46] Cobalt is not easily absorbed from the digestive tract. The body level of cobalt normally measures 80-300 mcg. It is stored in the RBCs and the plasma, as well as in the liver, kidney, spleen, and pancreas. [49],[50] Cobalt has both beneficial and harmful effects on human health. Cobalt is beneficial for humans because it is part of Vitamin B12, which is essential to maintain human health. Cobalt (0.16-1.0 mg cobalt/kg of body weight) has also been used as a treatment for anemia, including in pregnant women because it causes erythropoiesis. Cobalt also increases RBC production in healthy people, but only at very high exposure levels. [51] Deficiency of cobalt also leads to fatigue, digestive disorders, and neuromuscular problems. As cobalt's deficiency leads to decreased availability of B12, there is an increase of many symptoms and problems related to B12 deficiency, particularly pernicious anemia, and nerve damage. [51] Cobalt is excreted in both the urine and the feces, independent to the route of exposure (inhalation, injection or ingestion) most cobalt will be eliminated rapidly. [49] In one cohort study of people with hip prosthesis, there was a significant increase in the incidence of lymphatic and hematopoietic malignancies, and significant deficits of breast and colorectal cancer. [51]

Manganese (Mn)

Manganese content of foods varies greatly. Peterson and Skinner and Schroeder et al. found the highest concentrations in nuts, grains, and cereals; the lowest in dairy products, meat, poultry, fish, and seafood. Relatively high concentrations of manganese were found in soluble ("instant") coffee and tea and account for 10% of the total daily intake. [52] The total body content average human adult has about 15 mg of manganese, typically seen in nucleic acid. Daily requirement is about 2-5 mg/day. Manganese acts as an activator of enzyme and as a component of metalloenzymes. They have a role to play in oxidative phosphorylation, fatty acids and cholesterol metabolism, mucopolysaccharide metabolism, and urea cycle. [53] Manganese is found in all mammalian tissues with concentrations ranging from 0.3 to 2.9 μg manganese/g. Tissues rich in mitochondria and pigments (e.g., retina, dark skin) tend to have high manganese concentrations. Bone, liver, pancreas, and kidney typically have higher manganese concentrations than other tissues. The largest tissue store of manganese is in the bone. [53] Bone, liver, pancreas, and kidney typically have higher manganese concentrations than other tissues. The largest tissue store of manganese is in the bone. [53] In hydroxyapatite crystals of enamel, more than 49 elements are found, one of them being manganese, mostly in very small percentage. The concentrations of manganese in enamel are 0.08-20 ppm, equivalent 0.08-20 mg/kg, and in dentine are from 0.6 to 1000 ppm. Mn concentration is higher in the outer surface of enamel than in enamel-dentin border, and higher in permanent than in primary dentition. [54]

Some of the enzymes which are present along with magnesium are arginase, diamine oxidase, pyruvate carboxylate, phosphoglucomutase, succinate dehydrogenase, glutamine synthetase, superoxide dismutase. The deficiency cause bleeding disorders due to increased prothrombin time while accumulation over a long period causes anorexia, apathy, headache impotence, leg cramps, speech disturbance, encephalitis like syndrome and parkinsonian like syndrome. Psychosis may also occur. [55]

Selenium

The relationship between selenium and oral cancer has not yet been understood clearly, but there is some evidence observed that there is a relationship between selenium and Keshan syndrome. [55] Few studies have shown that prolonged deficiency of selenium produces this syndrome's features in animals such as failure growth in rats and muscle diseases in sheep. [56] A selenium responsive clinical syndrome in humans is described in some pathological conditions. In humans, they observed that those who take oral self-medication containing selenium causes muscular complications. [57] Low blood levels of selenium observed in some pathological conditions such as colonic, gastric and pancreatic carcinoma and cirrhosis. [58] Increased selenium intake may cause Keshan syndrome. [59] Keshan disease was first described in 1935 in North China. Clinically Keshan disease showed acute and chronic episodes of cardiogenic shock, enlarged heart, congestive heart failure, and cardiac arrhythmias. [60] The etiology of Keshan disease is still perplexing. There are numerous hypothesis suggested by different studies such as viral infections, environmental intoxication, mycotoxins, and nutritional deficiency. The hypothesis that relates with the deficiency of selenium is the most accepted hypothesis. [61]

Fluorine

Fluorine is a lightest element in Group VII of the periodic table, with atomic number 9. [62] Fluorine plays an important role in the hard tissues of the body such as bone and teeth. It helps in producing denser bones and fluoride has been suggested as a therapeutic agent in the treatment of osteoporosis. It is thought that fluoride, in conjunction with calcium, stimulates osteoblastic activity. It gets integrated into the bone matrix as fluorapatite which in turn increases the hardness of bones. Fluorine has profound anti-enzyme properties and prevents dental caries. The increased fluoride utilization could be responsible for the anticariogenic action. [63]

Fluoride or fluorine deficiency is a hypothetical disorder, which may cause increased dental caries and possibly osteoporosis due to a lack of fluoride in the diet. High levels of dietary fluoride cause fluorosis (bone disease) and mottling of teeth. High levels of fluoride cause dental lesions, periosteal hyperostosis, calcification of ligaments, and lameness. Crippling fluorosis in human is observed in persons exposed to very high intake (>20 mg/day) over a period of several years. Acute toxicity of fluoride is very rare and can occur due to a single ingestion of a large amount of fluoride and can be fatal. The amount of fluoride considered lethal when taken orally is 35-70 mg F/kg body weight. Symptoms of acute toxicity occur rapidly. There is a diffuse abdominal pain, diarrhea, vomiting, excess salivation, and thirst. Chronic toxicity is caused due to long-term ingestion of smaller amounts of fluoride in drinking-water. Excessive fluoride more than 8 ppm in drinking water daily for many years can lead to skeletal and dental fluorosis. Severe cases are normally found only in warm climates where drinking-water contains very high levels of fluoride. Due to chronic toxicity, bone density slowly increases; the joints stiffen and become painful. [64],[65]

Dental fluorosis may be easily recognized but the skeletal involvement is not clinically obvious until the advanced stage and early cases may be misdiagnosed as rheumatoid arthritis or osteoarthritis. Fluoride increases the stability of the crystal lattice in bone, but makes bone more brittle. The total quantity of fluoride ingested is the single most important factor in determining the clinical course of skeletal fluorosis; the severity of symptoms correlates directly with the level and duration of exposure. Bone changes observed in human skeletal fluorosis are structural and functional, with a combination of osteosclerosis, osteomalacia, osteoporosis and exostosis formation, and secondary hyperparathyroidism in a proportion of patients. At very high fluoride concentrations, stages 2 and 3 of skeletal fluorosis are likely to occur. The clinical signs of these stages are chronic joint pain, dose-related calcification of ligaments, osteosclerosis, possible osteoporosis of long bones, and in severe cases, muscle wasting, and neurological defects. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed. [66]

Iodine

Iodine is a vital micronutrient required at all stages of life; fetal life and early childhood being the most critical phases of requirement. Iodine is an essential constituent of the thyroid hormones thyroxine (T4 tetraiodothyronine) and (T3 triiodothyronine). [67] It also plays an important role in the functioning of the parathyroid glands. Iodine also promotes general growth and development within the body as well as aiding in metabolism. Because of its role in the metabolism, the symptoms of an iodine deficiency can be far reaching. Even though it is so important to proper functioning of the human organism, iodine deficiency is not uncommon. Severe iodine deficiency often occurs in individuals who have thyroid disease and are hyperthyroid or those who have a goiter from thyroid malfunction. Symptoms of iodine deficiency may include extreme fatigue, slowing of both physical and mental processes, weight gain, facial puffiness, constipation, and lethargy. Babies born to iodine deficient mothers may be lethargic and difficult to feed. If they are left untreated, it is likely that they will develop cretinism and end up suffering poor overall growth and mental retardation. [68]

Iodine overload is less common compared with its deficit though it is unfavorable, as well as a lack of it. The literature provides information demonstrating that intake of iodine from seaweeds is safe because iodine is organically bound and is not cumulated in the body. If its intake is exceeded, it is excreted with urine, mainly during the 1 st day. Organically bound iodine is harmless, even with prolonged use at high doses. For example, at intake of 1-5 mg of iodine with seaweeds by healthy people, all iodine is excreted with urine within 48 h. Only very high doses of organic iodine from seaweeds may cause unfavorable effects on the function of the thyroid gland. Excess iodine can cause as thyrotoxicosis so as hyperthyroidism as well as chronic thyroiditis, hashimoto's thyroiditis and even may increase the risk of thyroid gland cancer. [69]


  Clinical Significance of Essential Trace Elements Top


The clinical interest in trace metal determination for the diagnosis of different diseases has increased in recent years. Distribution of trace metal metabolism influences biochemical pathways in different fields of metabolism and causes characteristic diseases. Trace metal metabolism may be concerned with intake, dietary availability, absorption, distribution, storage, mobilization, biochemical activity, and excretion.


  Trace Elements and Fibrosis Top


Fibrosis of various organs and tissue have been studied, but only very few studies correlate the trace elements and fibrosis. The role of trace elements may be as a cofactor of any of enzyme involved in fibrosis. There are reports that trace elements abnormalities may be pathologically reflected as liver dysfunction leading to fibrosis. The antioxidant defenses in metal-induced liver damage, mainly iron, and copper overload is not fully understood due to a variety of perturbations in homeostasis. Levels of selected antioxidants may provide additional protection against liver injury and prevent progression of fibrosis and cirrhosis. [30]

Indian childhood cirrhosis leads to fibrosis. There are reports indicate that there are significant deposits of stainable copper in hepatocytes. Reports from Japanese literature say that excess iron and copper accumulation may cause liver damage and fibrosis. [70]

The action of molybdenum and tungsten upon collagen by the administration to rats, showed that there was a lower levels of cross-linking. It was concluded that tritopical binding of molybdenum and tungsten in the collagen is unlikely. The biological effect of these metals was due to competition with copper and the interference with physiological cross-linking reaction based on partial blockade of lysyl oxidase (LOX). The action of molybdenum for a long period in rats caused decreased collagen stability. The cobalt - chromium- molybdenum powder had no apparent effect on the growth of fibroblast when they were exposed to these metal powders in vitro studies. [54]

Role of trace elements in oral submucous fibrosis

  • Areca nut in any form have high level of soluble copper in them
  • The tissue of submucous fibrosis patients had increased copper and decreased zinc and iron than the normal patients
  • In submucous fibrosis patients, the serum levels showed decreased copper and increased zinc and iron contents than the normal patients.


This clearly shows that there exists a sort of interaction of metals copper, iron, and zinc. It is known fact that excess of iron produces a deficit of copper and zinc while an excess of zinc produces a deficit of copper and iron, it is assumed that the local increase of copper is due to the content of areca nut. The decrease of zinc and iron content may be attributed or secondary to an increase of copper levels. [30]

Dental aspects of trace elements

Since 1908, when in Texas Dental Society meeting at El Paso, mottled teeth were attributed to drinking-water; researches started on influence of trace elements on dental diseases. It was reported that about 41 elements are incorporated into a dental tissues during development of the tooth. The amount of each element reflected the environment which the process was exposed. After the development of hard dental tissue, there are only mild changes. Posteruptive uptake of trace elements is limited to surface and when restorations are done. [66]

Trace elements of teeth

Elements occurring above 1000 ppm are Na, Cl, and Mg. The elements that are found in a range of 100-1000 ppm are potassium, sulfur, zinc, silicone and Fl. While those are found b/w 10-100 ppm are iron, aluminum, lead, boron, and barium. 1-10 ppm of Cu, molybdenum, cadmium, iodine, titanium, chromium and Mg and found nickel, lithium, silver, selenium, cobalt are found in the range of 0.1-0.9 ppm. [71]

Trace elements in saliva

Saliva normally does not contain trace elements. If metal is found in excess quantities, they may be excreted via saliva. This may be reflected to diet, pollution or water. They in turn may affect the production of plaque, amount of saliva secreted, and metal concentration in saliva. [67]

Trace elements in dental caries

Of all the positive and negative interaction Fl, molybdenum, selenium and siliconium have been studied to produce cariostatic activity while interaction such as molybdenum - fluorine, molybdenum, copper, and siliconium - fluoride are primary interaction for cariostatic process. Cu acts as a caries promoting agent. [68]

Trace elements in dental soft-tissues

Epidermal parakeratosis in cheek, tongue, and esophagus is a sign of zinc deficiency. Thickening of the buccal mucosa is a common feature along with loss of filiform papillae. Deficiency of zinc could be loss of smell. [38]

Techniques to detect trace elements

Recently trace elements content of food and tissues has been created interest among research scholars. Such determinations required sensitivity and accurate methods of analysis. Most of the trace elements are estimated with a help of colorimetric and spectrographic methods of analysis. [69],[70]

Atomic absorption spectrometry-based on flames arcs and sparks (flame by electrothermal):

  • Emission spectroscopic methods.
  • Neutron activation analysis.
  • Electrochemical methods.
  • Isotope dilution mass spectrometry.
  • Atomic X-ray fluorescence spectroscopy.


For a single elements analysis, atomic spectroscopy and electrochemical methods are frequently applied. For multi elements tech, NAA and spectroscopic methods are used. [9]


  Obstacles Facing Elemental Analysis Top


The problem of analytical inaccuracy and sample contamination is the source of error in trace element studies. Accuracy in the analysis can be overcome by using properly graded instruments, avoiding operator bias, ambient temperature, and pressure. Sample contamination may occur at the collection device or storage devices or air or chemical reagents or lab instruments. The method should also include standard reference materials to avoid errors, in both sample storage and analysis. [9]


  Conclusion Top


The role of copper and other trace elements in LOX and submucous fibrosis may provide vital clue for the etiopathogenesis and enable to use inhibitors of the enzyme as antifibrotic agents. The ability of LOX to function as Ras recession gene product can provide an answer to the occurrence of carcinoma. The increased levels of copper and decreased levels of zinc and iron in biopsy specimen of oral submucous fibrosis when compared to normal may be sort of interaction with the serum levels that are reversed, decreased level of copper and increased level of zinc and iron in serum specimens of oral submucous fibrosis when compared to normal subjects. It is then also possible to relate anemia, a consistent finding with these diseases. Thus the deciphered role of trace elements and interaction of metals in LOX, will enable to understand the etiopathogenesis, provide a rapid diagnostic facility and also create effective treatment modalities.

 
  References Top

1.
Kienlen J. Deficiencies in trace elements during parenteral alimentation. Ann Anesthesiol Fr 1977;18:1019-34.  Back to cited text no. 1
    
2.
Frieden E. The chemical elements of life. Sci Am 1972;227:52-60.  Back to cited text no. 2
    
3.
Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 1995;18:321-36.  Back to cited text no. 3
    
4.
Wada O. What are trace elements? Their deficiency and excess states. J Japan Med Assoc 2004;47:351-8.  Back to cited text no. 4
    
5.
Nielsen FH. New essential trace elements for the life sciences. Biol Trace Elem Res 1990;26-27:599-611.  Back to cited text no. 5
    
6.
Bowen HJ. Trace Elements in Biochemistry. 2 nd ed. London: Academic Press; 1966. p. 55-7.  Back to cited text no. 6
    
7.
Frieden E. New perspectives on the essential trace elements. J Chem Educ 1985;62:917-23.  Back to cited text no. 7
    
8.
Frieden E. The evolution of metals as essential elements (with special reference to iron and copper). Adv Exp Med Biol 1974;48:1-29.  Back to cited text no. 8
    
9.
Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini M, et al. Trace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood and serum of Italian subjects. Sci Total Environ 1990;95:89-105.  Back to cited text no. 9
    
10.
Harris ED. Copper homeostasis: The role of cellular transporters. Nutr Rev 2001;59:281-5.  Back to cited text no. 10
    
11.
Hart EB, Steenbock H, Waddell J, Elvehjem CA. Iron in nutrition. VII. Copper as a supplement to iron for hemoglobin building in the rat 1928. J Biol Chem 2002;277:e22.  Back to cited text no. 11
    
12.
Deleves HT. Text Book of Biological Role of Copper. Ciba Foundation Symposium. Chichester, UK: John Wiley & Sons Inc.; 2009. p. 5-22.  Back to cited text no. 12
    
13.
Walravens PA. Nutritional importance of copper and zinc in neonates and infants. Clin Chem 1980;26:185-9.  Back to cited text no. 13
    
14.
Mason KE. A conspectus of research on copper metabolism and requirements of man. J Nutr 1979;109:1979-2066.  Back to cited text no. 14
    
15.
Turnlund JR. Human whole-body copper metabolism. Am J Clin Nutr 1998;67 5 Suppl:960S-4.  Back to cited text no. 15
    
16.
Odell BL. Biochemical basis of the clinical effects of copper deficiency.New York: Alan R Liss Inc; 1982. p. 301-13.  Back to cited text no. 16
    
17.
Todd WR, Elvehjem CA, Hart EB. Nutrition classics. Am J Physiol 1934;107:146-56.  Back to cited text no. 17
    
18.
Turnlund JR, Jacob RA, Keen CL, Strain JJ, Kelley DS, Domek JM, et al. Long-term high copper intake: Effects on indexes of copper status, antioxidant status, and immune function in young men. Am J Clin Nutr 2004;79:1037-44.  Back to cited text no. 18
    
19.
Watts DL. The nutritional relationships of copper. J Orthomol Med 1998;4:99-109.  Back to cited text no. 19
    
20.
Shetty SR, Babu S, Kumari S, Shetty P, Hegde S, Karikal A. Role of serum trace elements in oral precancerous and oral cancer - A biochemical study. J Cancer Res Treat 2013;1:1-3.  Back to cited text no. 20
    
21.
Vasudevan DM, Sreekumari S. Text Book of Biochemistry for Medical Students. 5th ed. New Delhi: Jaypee Publication; 2007. p. 76-91.  Back to cited text no. 21
    
22.
Lieu PT, Heiskala M, Peterson PA, Yang Y. The roles of iron in health and disease. Mol Aspects Med 2001;22:1-87.  Back to cited text no. 22
    
23.
Gil VM, Ferreira JS. Anemia and iron deficiency in heart failure. Rev Port Cardiol 2014;33:39-44.  Back to cited text no. 23
    
24.
Anand T, Rahi M, Sharma P, Ingle GK. Issues in prevention of iron deficiency anemia in India. Nutrition 2014;30:764-70.  Back to cited text no. 24
    
25.
Andrews NC. The iron transporter DMT1. Int J Biochem Cell Biol 1999;31:991-4.  Back to cited text no. 25
    
26.
Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta 2012;1823:1434-43.  Back to cited text no. 26
    
27.
Roy CN, Andrews NC. Recent advances in disorders of iron metabolism: Mutations, mechanisms and modifiers. Hum Mol Genet 2001;10:2181-6.  Back to cited text no. 27
    
28.
Rosati G, Riccardi F, Tucci A. Use of tumor markers in the management of head and neck cancer. Int J Biol Markers 2000;15:179-83.  Back to cited text no. 28
    
29.
Rajendran R, Vasudevan DM, Vijayakumar T. Serum levels of iron and proteins in oral submucous fibrosis (OSMF). Ann Dent 1990;49:23-5, 45.  Back to cited text no. 29
    
30.
Boult J, Roberts K, Brookes MJ, Hughes S, Bury JP, Cross SS, et al. Overexpression of cellular iron import proteins is associated with malignant progression of esophageal adenocarcinoma. Clin Cancer Res 2008;14:379-87.  Back to cited text no. 30
    
31.
Satyanarayana U, Chakrapani U. Essentials of Biochemistry. 2nd ed. Kolkata: Arunabha Sen Book and Allied (P) Ltd.; 2008. p. 210-27.  Back to cited text no. 31
    
32.
Halsted JA, Smith JC Jr, Irwin MI. A conspectus of research on zinc requirements of man. J Nutr 1974;104:345-78.  Back to cited text no. 32
    
33.
Todd WR, Elvehjem CA, Hart EB. Zinc in the nutrition of the rat. Nutr Rev 1980;38:151-4.  Back to cited text no. 33
    
34.
Favier M, Faure P, Roussel AM, Coudray C, Blache D, Favier A. Zinc deficiency and dietary folate metabolism in pregnant rats. J Trace Elem Electrolytes Health Dis 1993;7:19-24.  Back to cited text no. 34
    
35.
Watson TD. Diet and skin disease in dogs and cats. J Nutr 1998;128 12 Suppl:2783S-9.  Back to cited text no. 35
    
36.
Franklin RB, Costello LC. Zinc as an anti-tumor agent in prostate cancer and in other cancers. Arch Biochem Biophys 2007;463:211-7.  Back to cited text no. 36
    
37.
Tuormaa TE. Adverse effects of zinc deficiency: A review from the literature. J Orthomol Med 1995;10:149-64.  Back to cited text no. 37
    
38.
Das M, Das R. Need of education and awareness towards zinc supplementation: A review. Int J Nutr Metab 2012;4:45-50.  Back to cited text no. 38
    
39.
Atkin's PW, Shriver DF. Inorganic Chemistry. 3rd ed. New York: Freeman and Company; 1999. p. 156-9.  Back to cited text no. 39
    
40.
Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care 2004;27:2741-51.  Back to cited text no. 40
    
41.
Anderson RA. Chromium and parenteral nutrition. Nutrition 1995;11 1 Suppl:83-6.  Back to cited text no. 41
    
42.
Krejpcio Z. Essentiality of chromium for human nutrition and health. Pol J Environ Stud 2001;10:399-404.  Back to cited text no. 42
    
43.
Costa M, Klein CB. Toxicity and carcinogenicity of chromium compounds in humans. Crit Rev Toxicol 2006;36:155-63.  Back to cited text no. 43
    
44.
Shi XL, Dalal NS. Chromium (V) and hydroxyl radical formation during the glutathione reductase-catalyzed reduction of chromium (VI). Biochem Biophys Res Commun 1989;163:627-34.  Back to cited text no. 44
    
45.
Dayan AD, Paine AJ. Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000. Hum Exp Toxicol 2001;20:439-51.  Back to cited text no. 45
    
46.
Gustavsson P, Jakobsson R, Johansson H, Lewin F, Norell S, Rutkvist LE. Occupational exposures and squamous cell carcinoma of the oral cavity, pharynx, larynx, and oesophagus: A case-control study in Sweden. Occup Environ Med 1998;55:393-400.  Back to cited text no. 46
    
47.
Barceloux DG. Cobalt. J Toxicol Clin Toxicol 1999;37:201-6.  Back to cited text no. 47
    
48.
Yamagata N, Murata S, Torii T. The cobalt content of human body. J Radiat Res 1962;3:4-8.  Back to cited text no. 48
    
49.
Taylor NA, Marks TS. Food and nutrition board recommended daily allowances. J Hum Nutr 1974;32:165-77.  Back to cited text no. 49
    
50.
Christiansen JM, Poulsen OM, Thomsen M. A short-term cross-over study on oral administration of soluble and insoluble cobalt compounds: Sex differences in biological levels. Int Arch Occup Environ Health 1993;65:233-40.  Back to cited text no. 50
    
51.
Paternain JL, Domingo JL, Corbella J. Developmental toxicity of cobalt in the rat. J Toxicol Environ Health 1988;24:193-200.  Back to cited text no. 51
    
52.
Burch RE, Hahn HK, Sullivan JF. Newer aspects of the roles of zinc, manganese, and copper in human nutrition. Clin Chem 1975;21:501-20.  Back to cited text no. 52
    
53.
Rehnberg GL, Hein JF, Carter SD, Linko RS, Laskey JW. Chronic ingestion of Mn3O4 by rats: Tissue accumulation and distribution of manganese in two generations. J Toxicol Environ Health 1982;9:175-88.  Back to cited text no. 53
    
54.
Kamberi B, Hoxha V, Kqiku L, Pertl C. The manganese content of human permanent teeth. Acta Stomatol Croat 2009;43:83-8.  Back to cited text no. 54
    
55.
Van Rij AM, Thomson CD, McKenzie JM, Robinson MF. Selenium deficiency in total parenteral nutrition. Am J Clin Nutr 1979;32:2076-85.  Back to cited text no. 55
    
56.
Andrews ED, Hartley WJ, Grant AB. Selenium-responsive diseases of animals in New Zealand. N Z Vet J 1968;16:3-17.  Back to cited text no. 56
    
57.
Hickey F. Selenium in human and animal nutrition. N Z Agric 1968;18:1-6.  Back to cited text no. 57
    
58.
Shamberger RJ, Rukovena E, Longfield AK, Tytko SA, Deodhar S, Willis CE. Antioxidants and cancer. I. Selenium in the blood of normals and cancer patients. J Natl Cancer Inst 1973;50:863-70.  Back to cited text no. 58
    
59.
Chen X, Young G, Chen J, Chen X, Wen Z, Ge K. Studies on the relations of selenium and Keshan diseases. Biol Trace Elem Res 1980;2:91-107.  Back to cited text no. 59
    
60.
Tan JA, Hou SF, Zhu WY, Li RB, Zheng DX, Wang MY, et al. The Keshan disease in China: A study of geographical epidemiology. Acta Geogr Sin 1979;34:85-104.  Back to cited text no. 60
    
61.
Muth OH, Oldfield JE, Remmert LF, Schubert JR. Effect of selenium and vitamin E on the muscle diseases. Science 1958;128:1090-1.  Back to cited text no. 61
    
62.
National Academy of Sciences. The Relation of Selected Trace Elements to Health and Disease. Washington, D.C: National Academy of Sciences; 1974. p. 22-5.  Back to cited text no. 62
    
63.
Kaminsky LS, Mahoney MC, Leach J, Melius J, Miller MJ. Fluoride: Benefits and risks of exposure. Crit Rev Oral Biol Med 1990;1:261-81.  Back to cited text no. 63
    
64.
Aoba T, Fejerskov O. Dental fluorosis: Chemistry and biology. Crit Rev Oral Biol Med 2002;13:155-70.  Back to cited text no. 64
    
65.
Mellberg JR, Ripa LW. Flouride Metabolism. Fluorides in Preventive Dentistry - Theory and Clinical Applications. Chicago: Quintessence Publishing Co. Limited; 1983. p. 81-102.  Back to cited text no. 65
    
66.
Critchfield JW, Keen CL. Manganese +2 exhibits dynamic binding to multiple ligands in human plasma. Metabolism 1992;41:1087-92.  Back to cited text no. 66
    
67.
Neto JB. The essential role of zinc in growth. Nutr Res 1995;15:335-58.  Back to cited text no. 67
    
68.
Navia JM. Effect of minerals on dental caries. Adv Chem 1970;94:123-60.  Back to cited text no. 68
    
69.
Khanna S. Immunological and biochemical markers in oral carcinogenesis: The public health perspective. Int J Environ Res Public Health 2008;5:418-22.  Back to cited text no. 69
    
70.
Beshgetoor D, Hambidge M. Clinical conditions altering copper metabolism in humans. Am J Clin Nutr 1998;67 5 Suppl:1017S-21.  Back to cited text no. 70
    
71.
Schroeder HA, Balassa JJ, Tipton IH. Abnormal trace metals in man: Tin. J Chronic Dis 1964;17:483-502.  Back to cited text no. 71
    



 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Pathways of heavy metals contamination and associated human health risk in Ajay River basin, India
Umesh Kumar Singh,Balwant Kumar
Chemosphere. 2017; 174: 183
[Pubmed] | [DOI]
2 Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo
Tatjana Orct,Jasna Jurasovic,Vedran Micek,Dean Karaica,Ivan Sabolic
Journal of Trace Elements in Medicine and Biology. 2017; 40: 104
[Pubmed] | [DOI]
3 Association of soil selenium, strontium, and magnesium concentrations with Parkinson’s disease mortality rates in the USA
Hongbing Sun
Environmental Geochemistry and Health. 2017;
[Pubmed] | [DOI]
4 Binding energies of hydrated cobalt hydroxide ion complexes: A guided ion beam and theoretical investigation
Rebecca A. Coates,P. B. Armentrout
The Journal of Chemical Physics. 2017; 147(6): 064305
[Pubmed] | [DOI]
5 Significance of cardiac and iron profile alteration in diabetic patients
Nabil A. Hasona
Comparative Clinical Pathology. 2017; 26(4): 951
[Pubmed] | [DOI]
6 Indoor air pollution and its association with poor lung function, microalbuminuria and variations in blood pressure among kitchen workers in India: a cross-sectional study
Amarnath Singh,Chandrasekharan Nair Kesavachandran,Ritul Kamal,Vipin Bihari,Afzal Ansari,Parappurath Abdul Azeez,Prem Narain Saxena,Anil Kumar KS,Altaf Hussain Khan
Environmental Health. 2017; 16(1)
[Pubmed] | [DOI]
7 Enhancement of the antiproliferative activity of [RuCp(PPh3)2(dmoPTA-1?P)]+via its coordination to one {CoCl2} unit: synthesis, crystal structure and properties of [RuCp(PPh3)2-µ-dmoPTA-1?P:2?2N,N'-CoCl2](OTf)·0.25H2O
Zenaida Mendoza,Pablo Lorenzo-Luis,Franco Scalambra,José M. Padrón,Antonio Romerosa
Dalton Trans.. 2017; 46(25): 8009
[Pubmed] | [DOI]
8 Quantification of copper content with laser induced breakdown spectroscopy as a potential indicator of offal adulteration in beef
Maria P. Casado-Gavalda,Yash Dixit,David Geulen,Raquel Cama-Moncunill,Xavier Cama-Moncunill,Maria Markiewicz-Keszycka,Patrick J. Cullen,Carl Sullivan
Talanta. 2017; 169: 123
[Pubmed] | [DOI]
9 Concentrations of trace metals in tissues of Chionoecetes crabs (Chionoecetes japonicus and Chionoecetes opilio) caught from the East/Japan Sea waters and potential risk assessment
Dong-Woon Hwang,Minkyu Choi,In-Seok Lee,Kil-Bo Shim,Tae-Hoon Kim
Environmental Science and Pollution Research. 2017; 24(12): 11309
[Pubmed] | [DOI]
10 Regression of murine Ehrlich ascites carcinoma using synthesized cobalt complex
Entsar A. Saad,Mohamed M. Hassanien,Hatem A. El-mezayen,Nada M. ELmenawy
Med. Chem. Commun.. 2017; 8(5): 1103
[Pubmed] | [DOI]
11 Correlation between iron regulatory protein-1 (G-32373708A) and -2 (G-49520870A), gene variations and migraine susceptibility in southeast Iran: A case-control study
Nourollah Ramroodi,Mehdi Jahantigh,Tooba Nakhzari-Khodakheir,Nasrin Ranjbar,Nima Sanadgol
Egyptian Journal of Basic and Applied Sciences. 2017;
[Pubmed] | [DOI]
12 Hydration Control Through Intramolecular Degrees of Freedom: Molecular Dynamics of [Cu(II)(Imidazole)4]
Akshaya K. Das,Markus Meuwly
The Journal of Physical Chemistry B. 2017; 121(38): 9024
[Pubmed] | [DOI]
13 Socio-demographic, lifestyle, and dietary determinants of essential and possibly-essential trace element levels in adipose tissue from an adult cohort
Celia Rodríguez-Pérez,Petra Vrhovnik,Beatriz González-Alzaga,Mariana F. Fernández,Piedad Martin-Olmedo,Nicolás Olea,Željka Fiket,Goran Kniewald,Juan P. Arrebola
Environmental Pollution. 2017;
[Pubmed] | [DOI]
14 Biogenic and Risk Elements in Wines from the Slovak Market with the Estimation of Consumer Exposure
Magdalena Semla,Pavol Schwarcz,Ján Mezey,Lukasz J. Binkowski,Martyna Blaszczyk,Grzegorz Formicki,Agnieszka Gren,Robert Stawarz,Peter Massanyi
Biological Trace Element Research. 2017;
[Pubmed] | [DOI]
15 Integration of Instrumental Neutron Activation Analysis and Inductively Coupled Plasma – Optical Emission Spectrometry with Mathematical Modeling for the Elemental Analysis of Plants
Ammar M. Ebrahim,Hamid Bounouira,Mohammed Abdassalam,Elsadig Shiekheldin,Akram Joda,Khalid Embarch,Moussa Bounakhla,Abubakr M. Idris,Bernhard Michalke
Instrumentation Science & Technology. 2017;
[Pubmed] | [DOI]
16 Bioaccumulation and potential sources of heavy metal contamination in fish species in Taiwan: assessment and possible human health implications
Chi Thanh Vu,Chitsan Lin,Gavin Yeh,Maria Ching Villanueva
Environmental Science and Pollution Research. 2017;
[Pubmed] | [DOI]
17 Assessment of iodine importance and needs for supplementation in school-aged children in Portugal
Ana M. Pires,Sandra Félix,Ana C. C. Sousa
BMC Nutrition. 2017; 3(1)
[Pubmed] | [DOI]
18 Elaboration, sensorial acceptance and characterization of fermented flavored drink based on water-soluble extract of baru almond
Marceli Borges Fioravante,Priscila Aiko Hiane,José Antônio Braga Neto
Cięncia Rural. 2017; 47(9)
[Pubmed] | [DOI]
19 Cloud point extraction utilizable for separation and preconcentration of (ultra)trace elements in biological fluids before their determination by spectrometric methods: a brief review
Ingrid Hagarová
Chemical Papers. 2016;
[Pubmed] | [DOI]
20 Synthesis and characterization of photodynamic activity of an iodinated Chlorin p6copper complex
Paromita Sarbadhikary,Alok Dube,Pradeep Kumar Gupta
RSC Adv.. 2016; 6(79): 75782
[Pubmed] | [DOI]
21 The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model
Govindarajan Karthivashan,Aminu Umar Kura,Palanisamy Arulselvan,Norhaszalina Md. Isa,Sharida Fakurazi
PeerJ. 2016; 4: e2127
[Pubmed] | [DOI]
22 The Role of Blood Lead, Cadmium, Zinc and Copper in Development and Severity of Acne Vulgaris in a Nigerian Population
C.I. Ikaraoha,N.C. Mbadiwe,C.J. Anyanwu,J. Odekhian,C.N. Nwadike,H.C. Amah
Biological Trace Element Research. 2016;
[Pubmed] | [DOI]
23 A Review of Heavy Metal Concentration and Potential Health Implications of Beverages Consumed in Nigeria
Sylvester Izah,Iniobong Inyang,Tariwari Angaye,Ifeoma Okowa
Toxics. 2016; 5(1): 1
[Pubmed] | [DOI]
24 A Review on Heavy Metal Concentration in Potable Water Sources in Nigeria: Human Health Effects and Mitigating Measures
Sylvester Chibueze Izah,Neelima Chakrabarty,Arun Lal Srivastav
Exposure and Health. 2016; 8(2): 285
[Pubmed] | [DOI]
25 Nutritional Aspects of Essential Trace Elements in Oral Health and Disease: An Extensive Review
Preeti Tomar Bhattacharya,Satya Ranjan Misra,Mohsina Hussain
Scientifica. 2016; 2016: 1
[Pubmed] | [DOI]
26 Structural and component mining of nails using bioengineering techniques
P. Thatai,B. Sapra
International Journal of Cosmetic Science. 2016;
[Pubmed] | [DOI]
27 Biomonitoring of 29 trace elements in whole blood from inhabitants of Cotonou (Benin) by ICP-MS
Brice Yedomon,Alain Menudier,Florence Lecavelier Des Etangs,Ludovic Anani,Benjamin Fayomi,Michel Druet-Cabanac,Christian Moesch
Journal of Trace Elements in Medicine and Biology. 2016;
[Pubmed] | [DOI]
28 Evaluation of Serum Trace Element Levels and Superoxide Dismutase Activity in Patients with Inflammatory Bowel Disease: Translating Basic Research into Clinical Application
Erfan Mohammadi,Durdi Qujeq,Hassan Taheri,Karimollah Hajian-Tilaki
Biological Trace Element Research. 2016;
[Pubmed] | [DOI]
29 Assessment of Serum Trace Elements in Diarrheic Yaks (Bos grunniens) in Hongyuan, China
Zhaoqing Han,Rongrong Li,Kun Li,Muhammad Shahzad,Xiao Qiang Wang,Wenteng Jiang,Houqiang Luo,Gang Qiu,Fazul Nabi,Jiakui Li,Xianrong Meng
Biological Trace Element Research. 2015;
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Conclusion
Biological Class...
Categorical Clas...
Clinical Signifi...
Trace Elements a...
Obstacles Facing...
References
Article Tables

 Article Access Statistics
    Viewed20086    
    Printed93    
    Emailed1    
    PDF Downloaded2839    
    Comments [Add]    
    Cited by others 29    

Recommend this journal