Evaluation of antioxidant-oxidant status of saliva in recurrent aphthous stomatitis: A systematic review

Document Type: Review Article(s)


Assistant Professor, Department of Oral Medicine, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran


BACKGROUND AND AIM: Recurrent aphthous stomatitis (RAS) as a common oral lesion may be created due to oxidative stress. In this study, we intend to examine the salivary antioxidant-oxidant status in patients with RAS.
METHODS: In this review study, all English and Persian articles were searched by relevant keywords from the PubMed, ScienceDirect, Cochrane, Scopus and SID databases from 1995 to 30 March 2020. Two independent reviewers performed the study selection using the specified eligibility criteria. Finally, Newcastle-Ottawa Scale (NOS) method was used for the quality evaluation of studies.
RESULTS: A systematic search on the references led to the identification of 87 articles, of which 68 were excluded and finally, 19 articles were included in the study. The majority of the studies (86%) showed no significant decrease in the total antioxidant capacity (TAC). In 71% of the studies, the malondialdehyde (MDA) levels exhibited an increasing trend and in all studies, Glutathione peroxidase (GPx) had a decreasing trend; the results in relation to uric acid were contradictory.
CONCLUSION: Beyond the need for more extensive research in this area, it can be concluded that since RAS has multifactorial etiology, changes in the body’s antioxidant-oxidant status are considered as an effective factor along with other factors.


  1. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 2005; 43(11): 5721-32.
  2. Scully C, Felix DH. Oral medicine--update for the dental practitioner. Aphthous and other common ulcers. Br Dent J 2005; 199(5): 259-64.
  3. Slebioda Z, Szponar E, Kowalska A. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: Literature review. Arch Immunol Ther Exp (Warsz) 2014; 62(3): 205-15.
  4. Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am 2014; 58(2): 281-97.
  5. Akoglu G, Metin A, Kilinc F, Pektas SD, Isikoglu S, Akbas A, et al. Total serum oxidant/antioxidant status and arylesterase activity in recurrent aphthous stomatitis. Ann Dermatol 2013; 25(3): 273-7.
  6. Bagan J, Saez G, Tormos C, Gavalda C, Sanchis JM, Bagan L, et al. Oxidative stress and recurrent aphthous stomatitis. Clin Oral Investig 2014; 18(8): 1919-23.
  7. Avci E, Akarslan ZZ, Erten H, Coskun-Cevher S. Oxidative stress and cellular immunity in patients with recurrent aphthous ulcers. Braz J Med Biol Res 2014; 47(5): 355-60.
  8. Ozturk P, Belge KE, Ataseven A. Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis. J Trace Elem Med Biol 2013; 27(4): 312-6.
  9. Bilgili SG, Ozkol H, Takci Z, Ozkol HU, Karadag AS, Aslan M. Assessment of the serum paraoxonase activity and oxidant/antioxidant status in patients with recurrent aphthous stomatitis. Int J Dermatol 2013; 52(10): 1259-64.
  10. Tugrul S, Kocyigit A, Dogan R, Eren SB, Senturk E, Ozturan O, et al. Total antioxidant status and oxidative stress in recurrent aphthous stomatitis. Int J Dermatol 2016; 55(3): e130-e135.
11. Gupta I, Shetti A, Keluskar V, Bagewadi A. Assessment of serum enzymatic antioxidant levels in patients with recurrent aphthous stomatitis: A case control study. Enzyme Res 2014; 2014: 340819.

12. Rahmani M, Ghorchi V, Rezaei F, Vaisi-Raygani A. Evaluation of total antioxidant capacity of saliva in high school students. Glob J Health Sci 2015; 8(4): 89-94.

13. Boudin F, Nie JY, Bartlett JC, Grad R, Pluye P, Dawes M. Combining classifiers for robust PICO element detection. BMC Med Inform Decis Mak 2010; 10: 29.

14. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25(9): 603-5.

15. Rezaei F, Soltani T. Evaluation and comparison of total antioxidant capacity of saliva between patients with recurrent aphthous stomatitis and healthy subjects. Open Dent J 2018; 12: 303-9.

16. Jesija JS, Gopal S, Skiel HP. Recurrent aphthous stomatitis: An assessment of antioxidant levels in plasma and saliva. J Clin Diagn Res 2017; 11(9): ZC64-ZC67.

17. Ziaudeen S, Ravindran R. Assessment of oxidant-antioxidant status and stress factor in recurrent aphthous stomatitis patients: Case control study. J Clin Diagn Res 2017; 11(3): ZC01-ZC04.

18. Babaee N, Hosseinkazemi H, Pouramir M, Khakbaz BO, Salehi M, Khadir F, et al. Salivary oxidant/ antioxidant status and hematological parameters in patients with recurrent aphthous stomatitis. Caspian J Intern Med 2016; 7(1): 13-8.

19. Kiran GC, Reginald BA. Aphthous ulcers, salivary peroxidase and stress: Are they related? J Oral Maxillofac Pathol 2015; 19(1): 37-41.

20. Momen-Beitollahi J, Mansourian A, Momen-Heravi F, Amanlou M, Obradov S, Sahebjamee M. Assessment of salivary and serum antioxidant status in patients with recurrent aphthous stomatitis. Med Oral Patol Oral Cir Bucal 2010; 15(4): e557-e561.

21. Caglayan F, Miloglu O, Altun O, Erel O, Yilmaz AB. Oxidative stress and myeloperoxidase levels in saliva of patients with recurrent aphthous stomatitis. Oral Dis 2008; 14(8): 700-4.

22. Saral Y, Coskun BK, Ozturk P, Karatas F, Ayar A. Assessment of salivary and serum antioxidant vitamins and lipid peroxidation in patients with recurrent aphthous ulceration. Tohoku J Exp Med 2005; 206(4): 305-12.

23. Farhad Mollashahi L, Pouramir M, Motalebnejad M, Honarmand M, Bijani A, Shirzad A. Comparison of salivary total antioxidant capacity and lipid peroxidation in patients with recurrent aphthous stomatitis and healthy persons. J Babol Univ Med Sci 2013; 15(5): 39-44. [In Persian].

24. Khademi H, Khozeimeh F, Tavangar A, Amini S, Ghalayani P. The serum and salivary level of malondialdehyde, vitamins A, E, and C in patient with recurrent aphthous stomatitis. Adv Biomed Res 2014; 3: 246.

25. Al-Essa HS, Zaidan TF. Assessment of serum and salivary oxidant and total antioxidant status of patients with recurrent aphthous stomatitis in a sample of Basrah city. J Bagh College Dentistry 2013; 25(Special 1): 83-8.

26. Azizi A, Shah Siah S, Madhani A. Comparison of amount of salivary total antioxidant in patients with recurrent aphtous stomatitis. J Dent Med Tehran Univ Med Sci 2012; 25(1): 14-8. [In Persian].

27. SaxenaI S. Assessment of plasma and salivary antioxidant status in patients with recurrent aphthous stomatitis. Rev Sul-Bras Odontol 2011; 8(3): 261-5.

28. Karincaoglu Y, Batcioglu K, Erdem T, Esrefoglu M, Genc M. The levels of plasma and salivary antioxidants in the patient with recurrent aphthous stomatitis. J Oral Pathol Med 2005; 34(1): 7-12.

29. Prihanti AM, Savitri E D, Hernawan I. Measurement of malondialdehyde in patients with recurrent aphthous stomatitis. J Int Dent Med Res 2018; 11(1): 128-30.

30. Kaliamoorthy S, Sathishmuthukumar R, Chidambaram K, Srinivasan P, Nagarajan M, Selvakumar R, et al. Assessment of oral mucosal integrity status in patients with recurrent aphthous stomatitis. J Pharm Bioallied Sci 2019; 11(Suppl 2): S274-S277.

31. Ohashi M, Iwase M, Nagumo M. Elevated production of salivary nitric oxide in oral mucosal diseases. J Oral Pathol Med 1999; 28(8): 355-9.

32. Sunitha M, Shanmugam S. Evaluation of salivary nitric oxide levels in oral mucosal diseases: A controlled clinical trial. Indian J Dent Res 2006; 17(3): 117-20.

33. Jagtap K, Baad RK. Estimation of salivary nitric oxide in recurrent aphthous ulcer and oral lichen planus patients with its clinical significance. J Contemp Dent Pract 2012; 13(5): 623-6.

34. Abdolsamadi HR, Rezaei F, Goodarzi MT, Moghimbeigi A, Jazaeri M, Asadi S, et al. Comparison of salivary nitric oxide and epidermal growth factor level between diabetic patients and healthy individuals. IInt J Diabetes Dev Ctries 2015; 35(3): 477-82.

35. Ramezani GH, Moghadam MM, Saghiri MA, Garcia-Godoy F, Asatourian A, Aminsobhani M, et al. Effect of dental restorative materials on total antioxidant capacity and calcium concentration of unstimulated saliva. J Clin Exp Dent 2017; 9(1): e71-e77.

36. Mejean C, Morzel M, Neyraud E, Issanchou S, Martin C, Bozonnet S, et al. Salivary composition is associated with liking and usual nutrient intake. PLoS One 2015; 10(9): e0137473.