Beruflich Dokumente
Kultur Dokumente
CLINICAL
The role of saliva in
oral and systemic health
Juliette Reeves
27
CLINICAL
carcinogenic nitrosamines.14 15
Principal sources of ROS and RNS include smoking, alcohol, smoked
preserved foods and various beverages.
In addition to antioxidants, saliva also contains nitrosamine inhibitory
agents along with another crucial anti-cancer salivary enzyme glutathione
S-transferase.16 The salivary composition of patients with OSCC has been
found to be substantially altered with respect to free radical induced
mechanisms, with salivary RNS levels significantly higher and all salivary
antioxidants significantly reduced17.
More recently Hershkovich et al18 looked at the increased prevalence of
oral cancer among older people and suggested this may be due to an age
related reduction in protective salivary antioxidant mechanisms and age
related magnitude of oxidative stress from ROS and RNS exposure. A
decrease in salivary secretion and reduced ability to flow and arrive at the
sites where salivary protection is required adds to the reduced antioxidant
protective capacity of saliva.19 The reduction in saliva flow may be as a
result of age related changes to salivary gland function and/or multiple
medication use in the elderly.20
The development of oral cancer is multifactorial; however, whilst ROS
and RNS are involved in the initiation and progression of OSCC, both
are inhibited by antioxidants21. What is not clear is whether an increase
in ROS and RNS activity results in depletion of antioxidant availability
or if the opposite is true. In either case the pathogenesis of oral cancer
is related to the close contact between saliva and the mucosal tissues,
demonstrating the vital role salivary antioxidants may play in the
prevention of oral cancer.
Saliva and periodontal disease
The aetiology of periodontal disease is based on an imbalance between
bacterial challenge from species that colonise the oral cavity and host
response to these bacterial pathogens.22 Three primary species have been
identified as periodontal pathogens: Aggregatibacter actinomycetemcomitans
(AA), Tannerella forsythia (Bacteroides forsythus) and Porphyromonas gingivalis
(PG). Of these PG shows extensive proliferation in chronic periodontally
diseased patients.23
In response to bacterial invasion, the host immune response releases proinflammatory cytokines (IL-1, Il-6, Il-8, TNF) which recruit Polymorphonuclear
leukocytes (PMNs) to the site of infection.22 PMNs are the primary host
defense against periodontal pathogens. PMNs in periodontal patients
display an increase in number, adhesion and oxidative activity, releasing
ROS species such as superoxide. As the superoxide released is not target
specific oxidative damage to the surrounding tissues occurs24. These
mechanisms have identified ROS involvement in the aetiology of periodontal
disease along with lowered antioxidant levels implicating oxidative stress
in the pathology of periodontal disease.5 25
Several studies have demonstrated increased oxidative stress and depleted
antioxidant availability in periodontitis patients.26 Individuals with periodontal
disease have a significant increase in the activities of antioxidant systems in
gingival tissue compared to healthy controls, demonstrating a correlation
between oxidative stress biomarkers and periodontal disease.27 When high
levels of extracellular ROS exist antioxidant levels are suggested to play an
important role in the onset and development of inflammatory oral diseases.28
Chappel et al29 studied the antioxidant capacity of saliva in diseased and
healthy control groups and found significantly lower antioxidant capacity
28
DENTAL HEALTH
CLINICAL
Conclusion
The available evidence to date implicates pro-inflammatory mediated
oxidative stress in the pathogenesis of oral diseases and that local antioxidant
status may be important in determining the susceptibility, disease progression
and prevention of oxidative damage to mucous membranes. The presence
of salivary antioxidants surrounding the gingival crevice may be of major
importance in dampening down inflammatory processes initiated by
bacterial infection. Further research is needed to understand the influence
of nutrition on salivary antioxidant status that may lead to the development
of a nutritional strategy for the treatment and prevention of
inflammatory oral diseases.
References
1. Nagler RM, Klein I, Zarzhevsky N et al. Characterisation of the differentiated
antioxidant profile of human saliva. Free Rad Biol Med 2002; 32(3): 268-77.
2. Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in
human disease. Am J Med. 1991; 91(3C):14S-22S.
3. Poston L, Raijmakers MTM. Trophoblast oxidative stress, antioxidants and pregnancy
outcome - A review. Placenta 2004; 25(Suppl. A): S72-S78.
4. Wu HJ, Chi CW, Liu TY. Effects of pH on nicotine-induced DNA damage and oxidative
stress. J Toxicol Environ Health A. 2005; 68(17-18): 1511-23.
5. Sculley DV, Langley-Evans SC. Periodontal disease is associated with lower antioxidant
capacity in whole saliva and evidence of increased protein oxidation. Clin Sci (Lond) 2003;
105(2): 167-72.
6. Pendyala G, Thomas B, Joshi SR. Evaluation of total antioxidant capacity of saliva in
type 2 diabetic patients with and without periodontal disease: A case control study. North
AM J Med Sci 2013; 5(1): 51-57.
7. Saral Y, Coskun BK, Ozturk P et al. 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. Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal
diseases. Periodontol 2000. 1994; 5: 78-111.
24. Guarnieri C, Zucchelli G, Bernardi F et al. Enhanced superoxide production with no
change of the antioxidant activity in gingival fluid of patients with adult periodontitis.
Free Radic Res Commun 1991; 15(1): 11-6.
25. Waddington RJ, Moseley R, Embery G. Reactive oxygen species: a potential role in the
pathogenesis of periodontal diseases. Oral Dis. 2000; 6(3):138-51.
26. Panjamurthy K, Manoharan S, Ramachandran CR. Lipid peroxidation and antioxidant
status in patients with periodontitis. Cell Mol Biol Lett 2005: 10(2); 255-64.
27. Borges I Jr, Moreira EA, Filho DW, et al. Proinflammatory and oxidative stress markers in
patients with periodontal disease. Mediators Inflamm 2007; 2007: 45794.
28. Chapple ILC. Reactive oxygen species and antioxidants in inflammatory diseases. J Clin
Periodontol 1997: 24(5); 287-96.
29. Chapple ILC, Mason GI, Garner I, et al. Enhanced chemiluminescent assay for
measuring the total antioxidant capacity of serum, saliva and crevicular fluid. Ann Clin
Biochem 1997 Jul; 34 (Pt 4): 412-21.
30. Chapple ILC, Brock G, Eftimiadi C et al. Glutathione in gingival crevicular fluid and its
relation to local antioxidant capacity in periodontal health and disease. Mol Pathol. 2002;
55(6): 367-73.
31. Sculley D, Langley-Evans SC. Periodontal disease is associated with lower antioxidant
capacity in whole saliva and evidence of increased protein oxidation. Clin Sci (Lond) 2003;
105(2): 167-72.
32. Harpenau LA, Cheema AT, Zingale JA et al. Effects of nutritional supplementation on
periodontal parameters, carotenoid antioxidant levels, and serum C-reactive protein.
J Calif Dent Assoc 2011; 39(5): 309-12, 314-8.
33. Van der Velden U, Kuzmanova D, Chapple ILC. Micronutritional approaches to
periodontal therapy. J Clin Periodontol 2011; 38 Suppl 11: 142-58.
34. Zunt SL. Recurrent aphthous stomatitis. Dermato Clin 2003; 21(1): 33-39.
35. Natah SS, Konttinen YT, Enattah NS et al. Recurrent aphthous ulcers today: a review of
the growing knowledge. Int J Oral Maxillofac Surg 2004; 33(3): 221-34.
8. Office for National Statistics June 2012. http://www.ons.gov.uk/ons/rel/vsob1/cancer statistics-registrations--england--series-mb1-/index.html Accessed July 2013
36. Cimen MY, Kaya TL, Eskandari G et al. Oxidant/antioxidant status in patients with
recurrent aphthous stomatitis. Clin Exp Dermatol 2003: 28(6); 647-50.
37. Bilgili SG, Ozkol H, Takci Z et al. Assessment of the serum paraoxonase activity and
oxidant/antioxidant status in patients with recurrent aphthous stomatitis. Int J Dermatol
2013; Jul 8. doi: 10.1111/ijd.12084. [Epub ahead of print]
10. Welsh Cancer Intelligence and Surveillance Unit April 2012. http://www.wales.nhs.uk/
sites3/page.cfm?orgid=242&pid=59080 Accessed July 2013
11. Northern Ireland Cancer Registry October 2012. http://www.qub.ac.uk/research centres/nicr/CancerData/OnlineStatistics/ Accessed July 2013
12. Reznick AZ, Hershkovich O, Nagler RM. Salivaa pivotal player in the pathogenesis of
oropharyngeal cancer. Br J Cancer 2004; 91(1): 11118.
13. Ma N, Tagawa T, Hiraku Y,et al. 8-Nitroguanine formation in oral leukoplakia, a
premalignant lesion. Nitric Oxide 2006; 14(2): 13743.
14. Xia DS, Deng DJ, Wang SL. Destruction of parotid glands affects nitrate and nitrite
metabolism. J Dent Res 2003; 82(2): 10105.
38. Karincaoglu Y, Batcioglu K, Erdem T et al. The levels of plasma and salivary antioxidants
in the patient with recurrent aphthous stomatitis. J Oral Pathol Med 2005; 34(1): 7-12.
39. Calayan F, Miloglu O, Altun O et al. Oxidative stress and myeloperoxidase levels in
saliva of patients with recurrent aphthous stomatitis. Oral Dis 2008; 14(8): 700-4.
40. Babaee N, Mansourian A, Momen-Heravi F, et al. The efficacy of a paste containing
Myrtus communis (Myrtle) in the management of recurrent aphthous stomatitis: a
randomized controlled trial. Clin Oral Investig 2010; 14(1): 65-70.
41. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med
1998; 9(3): 306-21.
15. Deng DJ. Progress of gastric cancer etiology: N-nitrosamides 1999s. World J Gastroenterol
2000; 6(4): 61318.
16. Stich HF, Rosin MP, Bryson L. The inhibitory effect of whole and deproteinized saliva on
mutagenicity and clastogenicity resulting from a model nitrosation reaction. Mutat Res.
1982; 97(4): 28392.
17. Bahar G, Feinmesser R, Shpitzer T et al. Salivary analysis of oral cancer patients: DNA
and protein oxidation, reactive nitrogen species, and antioxidant profile. Cancer 2007;
109(1): 549.
18. Hershkovich O, Shafat I, Nagler RM: Age-related changes in salivary antioxidant profile:
Possible implications for oral cancer. J Gerontol A Biol Sci Med Sci. 2007; 62(4): 361-6.
19. Lee SK, Lee SW, Chung SC, Kim YK, Kho HS. Analysis of residual saliva and minor
salivary gland secretions in patients with dry mouth. Arch Oral Biol 2002; 47(9): 63741.
20. Shern RJ, Fox PC, Li SH. Influence of age on the secretory rates of the human minor
salivary glands and whole saliva. Arch Oral Biol 1993; 38(9):75561.
21. Sun Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 1990;
8(6): 58399.
22. Lamont RJ, Jenkinson HF. Life below the gum line: Pathogenic mechanisms of
29