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30 Volume 6 • Issue 1 January / March 2016 • Oral biology

RESEARCH ON THE VARIATION OF SOME BIVALENT CATIONS IN

PATIENTS WITH DISEASES OF THE ORAL CAVITY

Daniel PAVĂL1, Silvia MÂRŢU2, Mihai NECHIFOR3

1PhD Student, Pharmacology Department, “Gr. T. Popa” University of Medicine and Pharmacy Iasi, Romania 2Univ.Professor, Periodontology Department, “Gr. T. Popa” University of Medicine and Pharmacy Iasi, Romania 3Univ.Professor, Pharmacology Department, “Gr. T. Popa” University of Medicine and Pharmacy Iasi, Romania

Corresponding author: drdanypaval@gmail.com

Abstract

The concentration of bivalent cations affects a large number of processes that occur in the oro-maxillary region. A connection has been established between chronic periodontitis, on one side, and the salivary concentration of calcium, magnesium, zinc and copper and the concentration of magnesium in blood, on the other. Patients with suppurations on oro-maxillo-facial area show decreased blood calcium concentration and increased salivary magnesium concentration. In the synthesis of dental enamel, calcium, magnesium, zinc and copper play important roles. Changes in the salivary concentration of bivalent cations are directly involved in some maxillary diseases and in tooth decay.

Keywords: Ca, Cu, Mg, Zn, infections, teeth.

1. INTRODUCTION

Bivalent cations (Calcium, Magnesium, Zinc and Copper and many others) play important and complex roles in the human body, as they maintain the normal structure, function, and proliferation of cells. Variation of intra and extracellular cation concentration is present in the pathogenesis of many human diseases.

The oral cavity is a unique anatomical structure, wiht a series of characteristics

inluenced both by the external environment and

by the internal one, such as: the direct contact with food, air, the mechanical solicitations of all teeth during mastication, the permanent contact with blood, saliva and microbial commensal

lora. Salivary concentration of any type may inluence some pathological process occurring in

the oral cavity.

Calcium is the most abundant and important mineral present in the human body, the largest amounts – i.e., 99% - being stored in bones and teeth, while the remaining 1% occurs in the liquid

and soft tissues.The body needs calcium to maintain strong bones and to carry out several important functions. This cation is involved in the release of presynaptic neuromediators, membrane excitability, neurotransmitter release and muscle contraction, skeletal rigidity and biological signal transduction in the cell membrane. In some diseases of the oral maxillary and parotid gland cancers, the ratio between the salivary concentrations of calcium and

magnesium is signiicantly changed.

Zinc is an essential bivalent cation, normally found in the brain, muscles, bones, kidney, and liver, with the highest concentrations in the prostate and parts of the eye. It has multiple roles, containing in its structure at least 50 metallic enzymes, of which mention should be made of carboxypeptidase, DNA polymerases, RNA polymerases, Zn-Cu superoxide dismutase. Around 300 other enzymes are Zn-dependent. This cation plays a key role in reproduction, for

both sexes. Zinc deiciency reduces the maturation

of the oocyte, delays and perturbs ovulation. It also modulates the action of some hormones, such as insulin and hypophysargonatotrops, stimulates prolifelation of lymphocytes, macrophages and neutrophils and reduces the peroxidation process. This bivalent cation stimulates prolifelation of fibroblastsand synthesis of collagen, while maintaining the acid-base balance of our body.

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International Journal of Medical Dentistry 31 RESEARCH ON THE VARIATION OF SOME BIVALENT CATIONS IN PATIENTS WITH DISEASES OF THE ORAL CAVITY

activity of several enzymes, especially those that catalyze the transfer of electrons necessary for cellular respiration, iron oxidation, biosynthesis of neurotransmitters, porphyrin synthesis, etc. Blood copper circulation is mainly related to ceruloplasmin and, to a lower extent, to other plasmatic proteins. Cooper is an essential component of CuZn-superoxide dismutase (CuZnSOD). Mantaining the concentration of copper within normal values is important for a normal functioning of the human body.

Magnesium is a bivalent cation participating to many biochemical reactions, such as synthesis of proteins, glucides and lipids, membrane transport of ions, nucleic acid metabolism, synthesis and use of macroergic substances like adenosine triphosphate (ATP) and guanozin triphosphate (GTP). There exist more than 300 magnesium-dependent enzymes. The human body contains about 24-48 g magnesium, most of it (60%) being stored in the bones, as calcium and magnesium salts. Magnesium is predominantly an intracellular cation, only 0.5% being located

in the plasma and in the interstitial luid.

Plasma concentration is magnesium is of 1.2 -1.8 meg/l, being partially linked to albumin. Its membrane forms phospholipid complexes with Na +/ K+. It also acts as a physiological antagonist of calcium, being a non-competitive inhibitor of channels.

This cation has a reducing effect on apoptosis, while also reducing the sinaptic release of adrenaline and noradrenaline, for sedative purpose. At the level of the central nervous system, magnesium inhibits the sensitivity of nociceptive stimulation, due to the antagonistic role of its NMDA receptors, and has positive effects in post-operative pain management. Magnesium may act as a relaxation factor for the bronchial smooth muscle and, at the same time,

it modulates de inlammatory process, reduces the release of free radicals and, inally, relieves

the bronchospasm caused by asthma.

The rigid components of the dento-maxillary apparatus contain high concentrations of calcium and magnesium.The enamel elements contain 37.9% calcium (Ca+2), dentin elements - 25.9%, and the maxilla bone contains 22.5% calcium. The concentration of magnesium (Mg+2) is of 0.42% in the enamel elements, of 0.82% in dentin

elements, whereas the maxilla bone contains 0.26% magnesium.

Different cations influence the salivary

secretion rate and its composition. The inluence

of salivary secretion can be determined directly, from the action of salivary glands parenchyma, and indirectly, from the vegetative innervations of these glands. A high magnesium concentration

determines a signiicant reduction of salivary

amylase secretion through stimulation with acetylcholine. Stimulation of the parotid gland with Ach increases magnesium saliva concentration. Manea A. et. al. [1] observed no significant difference between the blood concentration of calcium and magnesium in persons with chronic periodontitis - either smokers or non–smokers – comparatively with healthy patients. The mechanisms of chronic and

acute inlammatory processes are determined by

bivalent cations variations.

Persons suffering with periodontitis have a

signiicantly lower calcium salivary concentration.

In both healthy people and those with periodontitis, smoking did not affect the level of salivary calcium. Magnesium salivary concentration is higher in persons with periodontitis, comparatively with the healthy ones. Magnesium salivary concentration is

signiicantly higher in smokers, comparatively

with non-smokers. The magnesium:calcium ratio showed high values in persons suffering with periodontitis. It is assumed that magnesium

reduces bacterial inlammation, an increased

salivary magnesium concentration possibly contributing to reducing periodontal

inlammation, as well.

Zinc inhibits the development of certain inflammatory processes. Zinc and copper recorded high values in people with chronic periodontitis. Zinc salivary concentration is higher in smokers than in non-smokers. The

level of salivary copper was not inluenced by

smoking.

Kiss [2] found out that the level of salivary calcium in persons with chronic and aggressive periodontitis (adult smokers and non-smokers)

is signiicantly higher than in non-smokers.

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32 Volume 6 • Issue 1 January / March 2016 • Daniel PAVĂL, Silvia MÂRŢU, Mihai NECHIFOR

no signiicant differences in the salivary calcium

concentration at patients with periodontitis, either smokers or non-smokers.

Manea A. et. al. [4] established a connection between chronic periodontitis and the salivary concentration of calcium, magnesim, zinc, copper and magnesium in blood. Affected by smoking are salivary calcium and magnesium.

Imbalances between the concentrations of

bivalent cations have multiple inluences upon

dental diseases. The magnesium present in tooth structure has a higher concentration in dentin than in the enamel. [5]

An increased level of magnesium in the tooth, associated with carbohydrate consumption, determines tooth decay. Okazaki M. et al. stated that magnesium increases the solubility of apatite crystals. [6]

Zinc concentration in the dental structures depends on genders, being higher in female subjects. The activity of dental osteoclasts depends on copper, as a result of its stimulating effect. A series of metallic cations is used to treat tooth decay.

2. MALIGNANT TUMOURS

OUT OF ALL HUMAN MALIGNANT TUMORS, THE ONES PRESENT IN THE

ORO-MAXILLO-FACIAL AREA

REPRESENT ABOUT 1–1.5%.

About 20% - 35% of salivary glands tumors are diagnosed as malignant.[7] Out of these, 63% are located in the parotid glands. [8]

Malignant salivary gland tumors appear as serious diseases, due to their high growth rate.

At present, parotid gland neoplasms show an increased incidence. [9]

Nagler R. and Dayan D. [10] consider that saliva composition is important for the development of malignant tumors, especially for squamous cell carcinoma.

Increasing of Zn2+ concentration is important for reducing the risk of appearance and development of malignant processes. Gradinaru I. et al. [11] observed that, in parotid gland malignant tumours (stages II-III), occurring in adults, the total salivary and serum magnesium concentrations are higher than in healthy persons.

A change has been also observed in the serum total Cu2+ / total Zn2+ ratio, which is lower than in healthy persons. Kopariski Z. et al. [12] found out that, in different forms of cancer, the

concentration of serum magnesium is modiied.

Some infections in the oro-maxillo-facial area cause major variations of the salivary and plasma concentrations of some cations, especially in cases of bacterial and fungal infections. The ratio between the concentrations of these cations plays a important role, acting upon bacteria and fungi through various mechanisms.

In persons with burning mouth syndrome, the salivary concentration of magnesium is

signiicantly lower, causing, according to the

study of Pekiner, an increased predisposition to depression and anxiety. [13]

Nechifor et al. [14] observed that the total salivary serum magnesium concentrations increase in persons with suppurations, comparatively with the healthy ones. Also, in patients with suppurations, a decrease in salivary calcium concentration is registered.

Domej W. et al. [15] found out that the concentration of zinc in blood is reduced in patients with severe infections of the oro-maxillo-facial area.

Prior to the treatment, the patients with oral bacterial suppurations have a increased total salivary magnesium and also a decreased zinc serum concentration. [14]

Low levels of zinc in both blood and tissues adversely affect the immune response.

The action of Histatin 5 is inhibited at high calcium concentrations. In the case of fungal infections, Histatin 5 has a strong fungistatic effect and also fungicidal properties. The action of Histatin 5 is inhibited by the increased salivary calcium concentration. Increasing of the Mg2+/ Ca2+ ratio in saliva represents a factor favoring fungal infections. [16]

Some materials used for prosthetic restorations and some drugs contain in their composition bivalent cations, which causes changes in the bivalent cations from the oro-maxillo-facial area.

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International Journal of Medical Dentistry 33 RESEARCH ON THE VARIATION OF SOME BIVALENT CATIONS IN PATIENTS WITH DISEASES OF THE ORAL CAVITY

of bivalent cations may favor the emergence and development of different pathological states, but they can also have a negative effect upon them.

References

1. Manea Al, Ciobanu C, Nechifor M. Inluence of smoking on the salivary and blood concentration of some bivalent cations in patients with chronic periodontitis. International Journal of Medical Dentistry. 2013; 3(1):57-64.

2. Kiss E, Sewon L, Gorzó I, Nagy K. Salivary calcium concentration in relation to periodontal health of female tobacco smokers: a pilot study. Quintessence Int. 2010;41(9):779-85.

3. Sutej I, Peros K, Benutic A, Capak K, Basic K, Rosin-Grget K. Salivary calcium concentration and periodontal health of young adults in relation to tobacco smoking. Oral Health Prev Dent. 2012; 10(4):397-403.

4. Manea A, Nechifor M. Research on plasma and saliva levels of some bivalent cations in patients with chronic periodontitis (salivary cations in chronic periodontitis). Rev Med Chir Soc Med Nat Iasi. 2014;118(2):439-49.

5. Hallsworth AS, Robinson C, Weatherbell JA. Mineral and magnesium distribution within the approximal carious lesion of dental enamel. Caries Res.1972;6(2):156-68.

6. Okazaki M, Takahashi J, Kimura H. Unstable behavior of magnesium-containing hydroxyapatites. Caries Res.1986; 20(4):324-31.

7. Fiorella R, Di Nicola V, Fiorella ML, Spinelli DA, Coppola F, Luperto P, Madami L. Major salivary gland diseases. Multicentre study. Acta Otorhinolaryngol Ital.2005;25(3):182-90.

8. Ascani G, Pieramici T, Messi M, Lupi E, Rubini C, Balercia P. Salivary gland tumours: a retrospective study of 454 patients. Minerva Stomatol. 2006;55(4):209-14.

9. Ostman J, Anneroth G, Gustafsson H, Tavelin B. Malignant salivary gland tumours in Sweden 1960-1989 – an epidemiological study. Oral Oncol.1997;33(3):169-76.

10. Nagler R, Dayan D. The dual role of saliva in oral carcinogenesis. Oncology. 2006;71(1-2):10-17. 11. Grădinaru I, Ghiciuc CM, Popescu E, Nechifor C,

Mândreci I, Nechifor M. Blood plasma and saliva levels of magnesium and other bivalent cations in patients with parotid gland tumors. Magnes Res. 2007;20(4):254-8

12. Kopartski Z, Puchalkski Z, Schlegel-Zawadska M, Golec EB, Opoka W, Nowak A, Szczepariski J. The serum magnesium content disturbances in patients with skin cancers. In: Anke M, Flakoswsky G, Kisters K, Schafer U, Schenkel H, Seifert M, Stoeppler M, editors, Macro and trace elements. Leipzig: Shubert-Verlag.2004;319-24.

13. Pekiner FN, Gümrü B, Demirel GY, Ozbayrak S. Burning mouth syndrome and saliva:detection of salivary trace elements and cytokines. J Oral Pathol Med. 2009;38(3):269-75.

14. Nechifor M, Gradinaru I, Popescu E, Gogalniceanu D, Mindreci I, Nechifor C. Variations of plasmatic and salivary concentrations of different bivalent cations in oro-maxillofacial area bacterial infections. In: Alpoim MC, Vasconcellos P, Santos MA, Armando JC, Jose AC, Philippe C Editors. Metal ions in biology and Medicine. Paris: John Libbey Eurotext.2006;9:556-60.

15. Domej W, Krachler M, Goessler W, Maier A, Irgolic KJ, Lang JK. Concentrations of copper, zinc, manganese, rubidium, and magnesium in thoracic empyema and corresponding sera. Biol Trace Elem Res. 2000;78(1-3):53-66.

16. Tsai H, Bobek LA. Human salivary histatins: promising anti-fungal therapeutic agents. Crit Rev Oral Biol Med. 1998;9(4):480-97.

17. Luca E, Crivoi F, Galeş C, Popescu E, Ciubotariu D, Nechifor M. Research on serum and saliva concentration of some bivalent cations in patient with suppurations of the oro-maxillo-facial area. Rev Med Chir Soc Med Nat Iasi. 2009;113(3):899-903. 18. Luca E, Nechifor M. Bivalent cations in oral

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