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BMC Oral Health. 2021 Dec 20;21(1):661. doi: 10.1186/s12903-021-02024-x.

Protease inhibitor concentrations in the saliva of individuals experiencing oral dryness.

BMC oral health

Kenkichi Yamamoto, Makiko Hiraishi, Mai Haneoka, Hidetake Fujinaka, Yoshitaka Yano

Affiliations

  1. Personal Health Care Products Research Laboratories, Kao Corporation, 2-1-3 Bunka, Sumida-ku, Tokyo, 131-8501, Japan. [email protected].
  2. Personal Health Care Products Research Laboratories, Kao Corporation, 2-1-3 Bunka, Sumida-ku, Tokyo, 131-8501, Japan.
  3. Analytical Science Research Laboratories, Kao Corporation, Tochigi, Japan.

PMID: 34930236 DOI: 10.1186/s12903-021-02024-x

Abstract

BACKGROUND: Oral dryness is a common symptom that may interfere with swallowing, chewing, and taste. The most common reason for oral dryness is hyposalivation. Some individuals experiencing oral dryness do not have hyposalivation, however, and the reverse is also true. Here, we focused on healthy individuals with a lower salivary flow rate and evaluated the relationship between the perception of oral dryness and salivary parameters to clarify the cause underlying the perception of oral dryness.

METHODS: A total of 59 participants were divided into 2 groups with a lower or higher salivary flow rate according to the median salivary flow rate. In participants with a lower salivary flow rate, we assessed salivary bacterial counts, protease activities, protein concentrations, oral parameters, and the subjective perception of oral dryness.

RESULTS: Protease activities and concentrations of protease inhibitors such as cystatin-D and cystatin-SA in the saliva of participants experiencing oral dryness were significantly higher and lower, respectively, than in those not experiencing oral dryness, even though no difference in the salivary flow rate was detected. Salivary cystatin-D and cystatin-SA concentrations correlated negatively with salivary protease activities.

CONCLUSIONS: The composition of salivary protease inhibitors and increased protease activities affect the subjective perception of oral dryness.

© 2021. The Author(s).

Keywords: Humans; Oral dryness; Peptide hydrolases; Salivary cystatins; Xerostomia

References

  1. Napeñas JJ, Brennan MT, Fox PC. Diagnosis and treatment of xerostomia (dry mouth). Odontology. 2009;97:76–83. - PubMed
  2. Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, et al. Preliminary criteria for the classification of Sjögren’s syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993;36:340–7. - PubMed
  3. Franzén L, Funegård U, Ericson T, Henriksson R. Parotid gland function during and following radiotherapy of malignancies in the head and neck. A consecutive study of salivary flow and patient discomfort. Eur J Cancer Oxf Engl. 1990;1992(28):457–62. - PubMed
  4. Nederfors T, Nauntofte B, Twetman S. Effects of furosemide and bendroflumethiazide on saliva flow rate and composition. Arch Oral Biol. 2004;49:507–13. - PubMed
  5. Soto-Rojas AE, Kraus A. The oral side of Sjögren syndrome. Diagnosis and treatment. A review. Arch Med Res. 2002;33:95–106. - PubMed
  6. Bardow A, Nyvad B, Nauntofte B. Relationships between medication intake, complaints of dry mouth, salivary flow rate and composition, and the rate of tooth demineralization in situ. Arch Oral Biol. 2001;46:413–23. - PubMed
  7. Suh K-I, Lee J-Y, Chung J-W, Kim Y-K, Kho H-S. Relationship between salivary flow rate and clinical symptoms and behaviours in patients with dry mouth. J Oral Rehabil. 2007;34:739–44. - PubMed
  8. van den Berg I, Pijpe J, Vissink A. Salivary gland parameters and clinical data related to the underlying disorder in patients with persisting xerostomia. Eur J Oral Sci. 2007;115:97–102. - PubMed
  9. Billings RJ, Proskin HM, Moss ME. Xerostomia and associated factors in a community-dwelling adult population. Commun Dent Oral Epidemiol. 1996;24:312–6. - PubMed
  10. Thorselius I, Emilson CG, Osterberg T. Salivary conditions and drug consumption in older age groups of elderly Swedish individuals. Gerodontics. 1988;4:66–70. - PubMed
  11. Närhi TO. Prevalence of subjective feelings of dry mouth in the elderly. J Dent Res. 1994;73:20–5. - PubMed
  12. Eliasson L, Birkhed D, Carlén A. Feeling of dry mouth in relation to whole and minor gland saliva secretion rate. Arch Oral Biol. 2009;54:263–7. - PubMed
  13. Inamura T, Ino C, Katoh M, Kishimoto A, Kumazawa H, Matsumoto A, et al. A simple method to estimate the secretion of saliva from minor salivary glands using iodine-starch reaction. Laryngoscope. 2001;111:272–7. - PubMed
  14. Weerkamp AH, Wagner K, Vissink A, Gravenmade EJ. Effect of the application of a mucin-based saliva substitute on the oral microflora of xerostomic patients. J Oral Pathol. 1987;16:474–8. - PubMed
  15. Almståhl A, Wikström M. Oral microflora in subjects with reduced salivary secretion. J Dent Res. 1999;78:1410–6. - PubMed
  16. Lamkin MS, Oppenheim FG. Structural features of salivary function. Crit Rev Oral Biol Med Off Publ Am Assoc Oral Biol. 1993;4:251–9. - PubMed
  17. Pramanik R, Osailan SM, Challacombe SJ, Urquhart D, Proctor GB. Protein and mucin retention on oral mucosal surfaces in dry mouth patients. Eur J Oral Sci. 2010;118:245–53. - PubMed
  18. Mizuhashi F, Koide K, Toya S, Takahashi M, Mizuhashi R, Shimomura H. Levels of the antimicrobial proteins lactoferrin and chromogranin in the saliva of individuals with oral dryness. J Prosthet Dent. 2015;113:35–8. - PubMed
  19. Kullander S, Sonesson B. Studies on saliva in menstruating, pregnant and post-menopausal women. Acta Endocrinol (Copenh). 1965;48:329–36. - PubMed
  20. Loe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand. 1963;21:533–51. - PubMed
  21. Löe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967;38(Suppl):610–6. - PubMed
  22. Organization WH. Oral health surveys : basic methods. World Health Organization; 1997. https://apps.who.int/iris/handle/10665/41905 . Accessed 9 Feb 2021. - PubMed
  23. Greene JG, Vermillion JR. The Simplified Oral Hygiene Index. J Am Dent Assoc. 1964;68:7–13. - PubMed
  24. Winkel EG, Roldán S, Van Winkelhoff AJ, Herrera D, Sanz M. Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis. A dual-center, double-blind placebo-controlled study. J Clin Periodontol. 2003;30:300–6. - PubMed
  25. Rosenberg M, Kulkarni GV, Bosy A, McCulloch CA. Reproducibility and sensitivity of oral malodor measurements with a portable sulphide monitor. J Dent Res. 1991;70:1436–40. - PubMed
  26. Farsi NMA. Signs of oral dryness in relation to salivary flow rate, pH, buffering capacity and dry mouth complaints. BMC Oral Health. 2007;7:15. - PubMed
  27. Kadowaki T, Yoneda M, Okamoto K, Maeda K, Yamamoto K. Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis. J Biol Chem. 1994;269:21371–8. - PubMed
  28. Molla A, Yamamoto T, Maeda H. Characterization of 73 kDa thiol protease from Serratia marcescens and its effect on plasma proteins. J Biochem (Tokyo). 1988;104:616–21. - PubMed
  29. Hamada R, Suehiro J, Nakano M, Kikutani T, Konishi K. Development of rapid oral bacteria detection apparatus based on dielectrophoretic impedance measurement method. IET Nanobiotechnol. 2011;5:25–31. - PubMed
  30. Ishihama Y, Oda Y, Tabata T, Sato T, Nagasu T, Rappsilber J, et al. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol Cell Proteom MCP. 2005;4:1265–72. - PubMed
  31. Pedersen AM, Bardow A, Jensen SB, Nauntofte B. Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Oral Dis. 2002;8:117–29. - PubMed
  32. Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function. J Prosthet Dent. 2001;85:162–9. - PubMed
  33. Villa A, Connell CL, Abati S. Diagnosis and management of xerostomia and hyposalivation. Ther Clin Risk Manag. 2014;11:45–51. - PubMed
  34. Ganeshnarayan K, Velliyagounder K, Furgang D, Fine DH. Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter actinomycetemcomitans. J Periodontal Res. 2012;47:661–73. - PubMed
  35. Ito T, Komiya-Ito A, Arataki T, Furuya Y, Yajima Y, Yamada S, et al. Relationship between antimicrobial protein levels in whole saliva and periodontitis. J Periodontol. 2008;79:316–22. - PubMed
  36. Yang H-W, Huang Y-F, Chou M-Y. Occurrence of Porphyromonas gingivalis and Tannerella forsythensis in periodontally diseased and healthy subjects. J Periodontol. 2004;75:1077–83. - PubMed
  37. Abe N, Kadowaki T, Okamoto K, Nakayama K, Ohishi M, Yamamoto K. Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease. J Biochem (Tokyo). 1998;123:305–12. - PubMed
  38. Alves MB, Motta ACF, Messina WC, Migliari DA. Saliva substitute in xerostomic patients with primary Sjögren’s syndrome: a single-blind trial. Quintessence Int Berl Ger. 1985;2004(35):392–6. - PubMed
  39. van Steenberghe D, Van den Eynde E, Jacobs R, Quirynen M. Effect of a lactoperoxidase containing toothpaste in radiation-induced xerostomia. Int Dent J. 1994;44:133–8. - PubMed
  40. Banoczy J, Dombi C, Czegledly A, Sari K. A clinical study with lactoperoxidase-containing gel and toothpaste in patients with dry mouth syndrome. J Clin Dent. 1994;5:65–9. - PubMed
  41. Kirstilä V, Lenander-Lumikari M, Söderling E, Tenovuo J. Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia. Acta Odontol Scand. 1996;54:391–7. - PubMed

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