Recurrent aphthous stomatitis (RAS) is one of the most common diseases of oral mucosa characterized by recurrent painful ulcers. Although many factors have been implicated in its etiology, they are not fully identified. To investigate the involvement of heavy metals accumulated in saliva in the etiopathogenesis of RAS. This is a prospective, comparative, and controlled clinical study investigating the relationship between heavy metal exposure and RAS. The study consisted of 75 patients with idiopathic RAS who presented to our clinic with recurrent oral wound complaints and 74 healthy volunteers. All subjects were interviewed regarding age, acute or chronic diseases, dietary habits, and possible chemical exposure. Lead (Pb), cadmium (Cd), mercury (Hg), copper (Cu), and manganese (Mn) was measured in saliva by inductively coupled plasma–mass spectrometer (ICP–MS). Significance was considered at p < 0.05. Salivary levels of Pb (15.2 ± 1.1 vs. 7.6 ± 9.9 μg/l; p < 0.003), Hg (0.50 ± 0.60 vs. 0.13 ± 0.30 μg/l; p < 0.001; p < 0.001), Cd (0.11 ± 0.14 vs. 0.06 ± 0.13 μg/l; p < 0.021), and Cu (34.9 ± 22.5 vs. 21.6 ± 21.9 μg/l; p < 0.001) were significantly higher in the patient group than that in the control group. There was no significant difference between Mn levels (57.9 ± 41.6 μg/l). Higher heavy metal content of saliva in the patients with RAS may induce apoptosis and ulcer in oral mucosa cells through triggering release of reactive oxygen species resulting from oxidative stress resulting DNA damage.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Ślebioda Z, Krawiecka E, Rozmiarek M, Szponar E, Kowalska A, Dorocka-Bobkowska B (2017) Clinical phenotype of recurrent aphthous stomatitis and interleukin-1β genotype in a Polish cohort of patients. J Oral Pathol Med 46:657–662
Gülseren D, Karaduman A, Kutsal D, Nohutcu RM (2016) The relationship between recurrent aphthous stomatitis, and periodontal disease and helicobacter pylori infection. Clin Oral Investig 20:2055–2060
Femiano F, Lanza A, Buonaiuto C, Gombos F, Nunziata M, Piccolo S, Cirillo N (2007) Guidelines for diagnosis and management of aphthous stomatitis. Pediatr Infect Dis J 26:728–732
Field E, Allan R (2003) Oral ulceration–aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic. Aliment Pharmacol Ther 18:949–962
Scully C, Gorsky M, Lozada-Nur F (2003) The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc 134:200–207
Jurge S, Kuffer R, Scully C, Porter SR (2006) Number VI recurrent aphthous stomatitis. Oral Dis 12:1–21
Duffus JH (2002) Heavy metals a meaningless term. Pure Appl Chem 74:793–807
Järup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182
Aslam B, Javed I, Khan FH, Rahman Z (2011) Uptake of heavy metal residues from sewage sludge in the goat and cattle during summer season. Pak Vet J 31:75–77
Özbolat G, Tuli A (2016) Effects of heavy metal toxicity on human health. Arch Med Rev J 25:502–521
Al-Saleh I, Shinwari N, Mashhour A (2003) Heavy metal concentrations in the breast milk of Saudi women. Biol Trace Elem Res 96:21–37
Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN (2014) Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 7:60–72
Martí-Cid R, Llobet JM, Castell V, Domingo JL (2008) Dietary intake of arsenic, cadmium, mercury, and lead by the population of Catalonia, Spain. Biol Trace Elem Res 125:120–132
Martorell I, Perelló G, Martí-Cid R, Llobet JM, Castell V, Domingo JL (2011) Human exposure arsenic, cadmium, mercury, and lead from foods in Catalonia, Spain: temporal trend. Biol Trace Elem Res 142:309–322
Farooq M, Anwar F, Rashid U (2008) Appraisal of heavy metal contents in different vegetables grown in the vicinity of an industrial area. Pak J Bot 40:2099–2106
Wang J, Chen C (2006) Biosorption of heavy metals by Saccharomyces cerevisiae: a review. Biotechnol Adv 24:427–451
Paknejad B, Shirkhanloo H, Aliomrani M (2019) Is there any relevance between serum heavy metal concentration and BBB leakage in multiple sclerosis patients? Biol Trace Elem Res 190:289–294
Lee JS, White KL (1980) A review of the health effects of cadmium. Am J Ind Med 1:307–317
Dapul H, Laraque D (2014) Lead poisoning in children. Adv Pediatr Infect Dis 61:313–333
Wadhwa N, Mathew BB, Jatawa S, Tiwari A (2012) Lipid peroxidation: mechanism, models and significance. Int J Curr Sci 3:29–38
Topcuoglu S, Ergül HA, Baysal A, Ölmez E (2003) Determination of radionuclide and heavy metal concentrations in biota and sediment samples from Pazar and Rize stations in the eastern Black Sea. Fresenius Environ Bull 12:695–699
Gonzales-Reimers E, Martin-Gonzalez C, Galindo-Martin L et al (2014) Lead, cadmium and zinc in hair samples: relationship with dietary habits and urban environment. Biol Trace Elem Res 157:205–210
Maduabuchi JM, Nzegwu CN, Adigba EO, Aloke RU, Ezomike CN, Okocha CE, Obi E, Orisakwe OE (2006) Lead and cadmium exposures from canned and non-canned beverages in Nigeria: a public health concern. Sci Total Environ 366:621–626
Istanbulluoglu H, Ogur R, Tekbas OF et al (2013) Heavy metal contamination in milk and dairy products. Turk Klin Tıp Bilim 33:410–419
Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M (2000) Recurrent aphthous stomatitis. Quintessence Int 31:95–112
Iebioda Z, Szponar E, Kowalska A (2014) Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch Immunol Ther Exp 62:205–215
Babaee N, Hosseinkazemi H, Pouramir M, Khakbaz Baboli O, Salehi M, Khadir F, Bijani A, Mehryari M (2016) Salivary oxidant/antioxidant status and hematological parameters in patients with recurrent aphthous stomatitis. Caspian J Intern Med 7:13–18
Zhang Z, Li S, Fang H (2017) Enzymatic antioxidants status in patients with recurrent aphthous stomatitis. J Oral Pathol Med 46:817–820
Saral Y, Coskun BK, Ozturk P, Karatas F, Ayar A (2005) Assessment of salivary and serum antioxidant vitamins and lipid peroxidation in patients with recurrent aphthous ulceration. Tohoku J Exp Med 206:305–312
Cimen MY, Kaya TI, Eskandari G, Tursen U, Ikizoglu G, Atik U (2003) Oxidant/antioxidant status in patients with recurrent aphthous stomatitis. Clin Exp Dermatol 28:647–650
Karaer A, Tuncay G, Tanrikut E, Ozgul O (2018) Blood cadmium concentrations in women with ectopic pregnancy. Biol Trace Elem Res 184:42–46
Forte G, Fadda C, Bocca B, Erre GL, Passiu G, Madeddu R (2019) Association between exposure to heavy metals and systemic sclerosis: the levels of Al, Cd, Hg, and Pb in blood and urine of patients. Biol Trace Elem Res 190:1–10
Khlifi R, Olmedo P, Gil F, Chakroun A, Hammami B, Hamza-Chaffai A (2015) Heavy metals in normal mucosa and nasal polyp tissues from Tunisian patients. Environ Sci Pollut Res Int 22:463–471
The authors wish to thank Asst. Prof. Dr. Korhan Kılıç for the statistical data and Prof. Dr. Armağan Hayırlı for grammatical editing.
This study was supported by Scientific Research Projects Coordination Unit (project no. TTU-2018-6512), Ataturk University, Erzurum, Turkey.
The study was approved by the ethics committee of University (approval date 09.06.2017, decision no 2017/0035). All patients and healthy subjects in the control group were informed about the study and written consent was obtained.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Öner, Ü., Özdemir, Ş., Öner, F. et al. Do Heavy Metals Accumulated in Saliva Involve in the Etiopathogenesis of Recurrent Aphthous Stomatitis?. Biol Trace Elem Res 198, 46–50 (2020). https://doi.org/10.1007/s12011-020-02058-2
- Recurrent Aphthous stomatitis
- Heavy metals
- Oxidative stress