Babu N. A, Masthan K. M. K, Balachander N, Gopalakrishnan T, Elumalai M. Biomarkers in Saliva. Biomed Pharmacol J 2012;5(2)
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N. Aravindha Babu1, K. M. K. Masthan1, N. Balachander1, T. Gopalakrishnan1 and M. Elumalai2

1Department of Oral Pathology and Microbiology, Sree Balaji Dental College and Hospital, Bharath University, Chennai, India. 2Department of Pharmacology, Sree Balaji Dental College and Hospital, Bharath University, Chennai, India.

Abstract

The components of saliva act as a “mirror of the body’s health”. Saliva contains biomarkers derived from serum, gingival crevicular fluid and mucosal transudate. Saliva helps individuals, researchers and health care professionals as a diagnostic tool. Since using saliva is safe, non-invasive, inexpensive, less time consuming it can also be used in community health programs. It helps to detect diseases and to improve the general health of the public. This review article gives details about salivary biomarkers and their role in diagnosis of systemic disorders.

Keywords

Biomarkers; Saliva; Systemic disorders; Gingival crevicular fluid

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Babu N. A, Masthan K. M. K, Balachander N, Gopalakrishnan T, Elumalai M. Biomarkers in Saliva. Biomed Pharmacol J 2012;5(2)

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Babu N. A, Masthan K. M. K, Balachander N, Gopalakrishnan T, Elumalai M. Biomarkers in Saliva. Biomed Pharmacol J 2012;5(2). Available from: http://biomedpharmajournal.org/?p=2552

Introduction

Saliva is mainly secreted by 3 major glands (parotid, submandibular and sublingual) and

many other minor salivary glands, which provides the basic functions like lubrication and

helps in taste, speech and digestion. The secretions from these glands is mixed with bronchial, nasal secretions, gingival crevicular fluid, blood constituents from bleeding gums, bacteria, virus, fungi, exfoliated epithelial cells and the food debris1, 2.

It has been used as a diagnostic medium for several years now3, 4, 5. Saliva contains biomarkers derived from serum, gingival crevicular fluid and mucosal transudate. Systemic and oral diseases produce markers that appear in saliva. Unstimulated saliva contains higher concentration of diagnostic biomarkers than stimulated saliva and is used commonly for the diagnostic purpose. It is because, stimulated saliva has low concentrated proteins6, 7 and variation in pH, due to the foreign substances (citric acid) that are used to stimulate salivary secretion. Apart from diagnosing various diseases, drug abuse can also be detected through salivary samples under drug monitoring system8.

The advantages of using saliva as a diagnostic aid are, it is safe, non-invasive, cost effective, time saving and can be used in mass screening5, 9. The salivary biomarkers and their role in diagnosis of various systemic disorders are briefed in this article.

Discussion

Saliva is used as a diagnostic medium for diseases such as, Oncology (Oral Squamous Cell Carcinoma, Cervical Cancer and Breast Cancer), Cardiovascular Diseases, and Infectious

Diseases (Viral Diseases, Bacterial Infections, Fungal Infections), Endocrinology, Autoimmune Diseases (Sjogren’s syndrome) and Psychiatry. Biomarkers are defined as cellular, biochemical and molecular characteristics by which normal/abnormal processes can be recognized and/or monitored.

The biomarkers for various diseases are as listed below.

Oncology

Saliva would be ideal for screening pre-malignant and malignant neoplasms because of its anatomical proximity. The bio markers are p53 antibody which can be detected in oral squamous cell carcinoma10, high level of salivary kallikrein in oral malignant tumors11, 12, 13 and Ca-125, a glycoprotein for ovarian cancer14.

Cardiovascular diseases

Cardio vascular diseases are the major cause for high mortality rate across the world. Salivary markers can be used for follow up after surgery. Determination of salivary amylase activity before and 6hrs after cardiovascular surgery shows more mortality in patients with low salivary amylase pre operatively.15

Infectious diseases

Viral diseases

Beta 2 micro globulin and soluble tumor necrosis factor are high in HIV patients.16, 17 Acute hepatitis A & B are diagnosed based on the level of IgM antibodies in saliva.18

Bacterial infections

Presence of helicobacter pylori in saliva is a sign of peptic ulcer19, 20. Saliva can be used as a tool for the detection of dental plaque – induced diseases, i.e. dental caries and gingivitis21, 22.

Fungal infections

Saliva can be used for the detection of oral candidiasis and salivary fungal counts23.

Endocrinology

Hormone levels can be monitored with the aid of saliva. Estradiol, Estriol, Cortisol, Testosterone, Salivary Aldosterone, Salivary Progesterone are the hormones that can be accurately assessed from saliva. Diabetes mellitus affects rate of flow & composition of saliva. Salivary alterations include higher levels of IgA, salivary peroxidase, glucose content, potassium, salivary total protein & amylase24.

Sjogren’s syndrome

It is a chronic autoimmune disorder noted by salivary and lacrimal gland dysfunction along with rheumatoid arthritis. A raised concentration of NaCl, IgA, IgG, lactoferrin, inflammatory mediators such as PGE2, TXB2, interleukin-2 and interleukin-625, 26, 27 are noted in the saliva of Sjogren’s syndrome patient.

Psychiatry

Objective Outcome Measures can be deciphered with the help of saliva during psychiatry. The therapeutic responses in the treatment of anxiety can be measured with salivary MHPG- (3-methyl 4-hydroxyphenyl glycol). 28

Drug monitoring

Saliva can be used to detect and monitor drugs like cocaine, opioids, barbiturates, diazepines, cotinine, cannabinoids and ethanol.29, 30, 31, 32

Conclusion

Although challenges remain ahead, the use of saliva – based oral fluid diagnostics appear promising for future application to diagnose diseases and to prognosticate treatment outcomes. More case controlled and longitudinal studies are needed in near future to validate these biomarkers and impregnate these into regular clinical practice, in a cost effective way for the benefit of mankind.

References

  1. Mandel, I.D., “The functions of saliva”. J. Dent. Res. 66: 623–7. (1987).
  2. Sreebny, L.M.., “Salivary flow in health and disease”. Compend. Suppl.13: 461–9 (1989).
  3. Kaufman, E., and Lamster, I., “The diagnostic applications of saliva: A Review”. Crit. Rev. Oral. Biol. Med. 13: 197–212. (2002).
  4. Streckfus, C.F., Bigler, L., Navazesh, M., Al-Hashimi, L., “Cytokine concentrations in stimulated whole saliva among patients with primary Sjogren’s, secondary Sjogren’s syndrome, and primary Sjogren’s syndrome receiving varying doses of interferon for symptomatic treatment of the condition: A preliminary study”. J. Clin. Oral Invest. 5: 133. (2001).
  5. Malamud, D., “Saliva as a diagnostic fluid”. Br. Med. J. 8: 207–8. (1992).
  6. Oberg, S.G., Izutsu, K.T., Truelove, E.L.,. “Human parotid saliva protein composition: Dependence on physiological factors”. Am. J. Physiol. 242(3): 231-236. (1982)
  7. Rudney, J. D., Kajander, K.C., Smith, Q.T., “Correlations between human salivary levels of lysozyme, lactoferrin, salivary peroxidase and secretory immunoglobulinA with therapies”. Caries Res. 38: 241–6. (2004).
  8. Bosker, W. M., and Huestis, M.A., “Oral fluid testing for drugs of abuse”. Clin. Chem, 55: 1910–31. (2009).
  9. Samaranayake, L., “Saliva as a diagnostic fluid”. Int. Den.t J.57: 295–9 (2007).
  10. Boyle, J.O, Mao, L., Brennan, J.A., “Gene mutations in saliva as molecular markers for head and neck Squamous Cell Carcinomas”. Am. J. Surg. 168: 429-432. (1994).
  11. Jenzano, J.W., Courts, N.F., Timko, D.A., Lundblad, R.L., “Levels of glandular kallikrien in whole saliva obtained from patients with solid tumors remote from the oral cavity”. J. Dent. Res. 65: 67-70. (1986a).
  12. Jenzano, J.W., Daniel, P.A., Kent, R.T., Leal, J.L., Koth, D.L., “Evaluation of kallikrein in human parotid and submandibular saliva”. Arch. Oral. Biol. 31: 627-628. (1986b).
  13. Jenzano, J.W., Brown, C.K., Mauriello, S.M., “Temporal variations of glandular kallikrein, protein and amylase in mixed human saliva”. Arch. Oral. Biol. 32: 757-759. (1987).
  14. Di-Xia, C., Schwartz, P., Fan-Qin, L., “Salivary and serum Ca 125 assays for detecting malignant ovarian tumours”. Obstet. Gynecol. 75: 701-704. (1990).
  15. Adam, D.J., Milne, A.A., Evans, S.M., “Serum amylase Isoenzymes in patients undergoing operation for ruptured and non-ruptured abdominal aortic aneurysm”. J .Vasc.Surg. 30: 229-235. (1999 ).
  16. Grant, R.M., Piwowar, E.M., Katongole-Mbidde, E., “Comparison of saliva and serum for human immunode®- Ciency virus Type 1 antibody testing in uganda using a rapid recombinant assay”. Clin. Diag. Lab. Immunol. 3: 640-644. (1996).
  17. Nishanian, P., Aziz, N., Chung, J., Detels, R., Fahey, J.L., “Oral ¯uids as an alternative to serum for measurement of markers of Immune activation”. Clin. Diagn. Lab.Immunol. 5: 507-512. (1998).
  18. Bello, P.Y., Pasquier, C., Gourney, P., Puel, J., Izopet, J., “Assessment of a Hepatitis C virus antibody assay in saliva for epidemiological studies”. Eur J Clin Microbiol Infect Dis 17: 570-572. ( 1998).
  19. Elsana, S., Sikuler, E., Uaari, A., “HCV antibodies in saliva and urine”. J Med Virol 55: 24-27. (1998).
  20. Kountoruras, J., “Diagnostic tests for Helicobacter Pylori”. Gut. 42: 900-901. (1998).
  21. Togelius, J., Kristoffersson, K., Anderson, H., Bratthall, D.,“Streptococcus mutans.saliva: Intra individual variations and relation to the number of colonized sites”.Acta Odontol. Scand. 42: 157-163. (1984).
  22. Stecksen-Blicks, C., “Salivary counts of Lactobacilli and Streptococcus Mutans. Caries prediction”. Scand. J. Dent. Res. 93: 204-212. (1985).
  23. Herenia, P., Lawrence., “Salivary markers of systemic disease: Non– invasive diagnosis of disease and monitoring of general health”. Can. Dent. Assoc. 68(3): 170-4. (2002).
  24. Sathya Priya, S., “Potential of salivary protein as a biomarker in prognosis of diabetes mellitus”. J. Pharm. Research. 4(7): 228-229. (2011).
  25. Fox, P.C., Spreight, P.M., “Current concepts of autoimmune exocrinopathy: immunologic mechanisms in the salivary pathology of Sjogren’s syndrome”. Crit. Rev. Oral Biomedical. 7: 144-158. (1996).
  26. Rhodus, N., Dahmer, L., Lindemann, K., Rudney, J., Mathur, A., Bereuter, J., “Siga and cytokine levels in whole saliva of Sjogren’s syndrome patients before and after oral pilocarpine hydrochloride administration: A Pilot study”. Clin. Oral Invest. 2: 191-196. (1998).
  27. Streckfus, C.F., Bigler, L., “Saliva as a diagnostic fluid”. Oral. Dis.8: 69–76. (2002).
  28. Schramm, W., Pomerleau, O.F., Pomerleau, C.S., Grates, H.E., “Cotinine in an ultra®ltrate of saliva”. Prev. Med. 21: 63-73. (1992a).
  29. Schramm, W., Smith, R.H., Craig, P.A., Kidwell, D.A., “Drugs of abuse in saliva: A review”. J. Anal. Tox. 16: 1-9. (1992b).
  30. Schramm, W., Smith, R.H., Craig, P.A., “Methods of simpli®ed saliva collection for the measurement of drugs of abuse, therapeutic drugs, and other molecules”. Ann. Ny. Acad. Sci. 694: 311-313. (1993).
  31. Smolle, K.H., Hofmann, G., Kaufmann, P., Lueger, A., Brunner, G., “Q.E.D. Alcohol test: A simple and quick method to detect ethanol in saliva of patients in emergency departments. Comparison with the conventional determination in blood”. Intensive Care Med .25: 492-495. (1999).
  32. Yamada, S., Yajima, J., Harano, M.  “Saliva level of free 3-methoxy-4 hydroxyphenylglycol in psychiatric outpatients with anxiety”. Int. Clin. Psychopharmacol. 13: 213-217. (1998).
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