La saliva: una potencial herramienta en la Odontología

Autores/as

  • Silvina Barembaum Universidad Nacional de Córdoba, Facultad de Odontología
  • Ana Azcurra Universidad Nacional de Córdoba, Facultad de Odontología

Palabras clave:

proteínas y péptidos salivales, biomarcadores, caries dental, enfermedades periodontales, cáncer oral

Resumen

La saliva es un líquido biológico de composición compleja que facilita las interacciones entre las células del huésped, los microorganismos bucales y los moduladores inmunológicos con el principal propósito de mantener el estado de salud bucal. Dentro de los componentes salivales, las proteínas son fundamentales por ser responsables de las principales funciones de la saliva. Los estudios proteómicos contribuyeron a identificar y caracterizar entre 2.000 a 2.600 proteínas y péptidos diferentes en su composición. Entre ellas, una alta proporción son glucoproteínas, como las mucinas, proteínas ricas en prolina e inmunoglobulinas, aglutininas, lactoferrina, cistatinas y lisozima. Además la saliva posee péptidos de potente actividad antimicrobiana y de protección a los tejidos minerales, como la catelicidina LL-37, ? y ? defensinas, histatinas y estaterinas. En particular, en los últimos años se ha profundizado la selección de biomarcadores de las enfermedades bucales como caries dental, enfermedades periodontales y cáncer bucal, considerando la sencilla, económica y poco invasiva obtención de este fluido, por lo que se ha impulsado el desarrollo de tecnologías para la detección de biomarcadores con alta sensibilidad y especificidad para una gran variedad de enfermedades bucales. El estudio de los componentes de la saliva y sus potenciales biomarcadores convierte a este fluido en una potente herramienta de diagnóstico y detección de enfermedades, como así también para evaluar la evolución de tratamientos terapéuticos, debido a que refleja el estado fisiológico y patológico del cuerpo.

Referencias

1.Rathnayake N, Gieselmann DR, Heikkinen AM, Tervahartiala T, Sorsa T. Salivary Diagnostics-Point-of-Care diagnostics of MMP-8 in dentistry and medicine. Diagnostics (Basel) 2017;7(1)pii: E7.

2. Juárez RP, Celía, AC. Rol de la saliva en la homeostasis de la cavidad bucal y como medio de diagnóstico. Rev Dent Chile 2015;106(2):15-8.

3. Uneyama H, Kawai M, Sekine-Hayakawa Y, Torii K. Contribution of umami taste substances in human salivation during meal. J Med Invest 2009;56 Suppl:197-204.

4. Abdul Rehman S, Khurshid Z, Hussain Niazi F, Naseem M, Al Waddani H, Sahibzada HA, et al. Role of Salivary Biomarkers in Detection of Cardiovascular Diseases (CVD). Proteomes 2017; 5(3): 21.

5. Scarano E, Fiorita A, Picciotti PM, Passali GC, Calò L, Cabras T, et al. Proteomics of saliva: personal experience. Acta Otorhinolaryngol Ital 2010;30(3):125-30.

6. Siqueira WL, Custodio W, McDonald EE. New insights into the composition and functions of the acquired enamel pellicle. J Dent Res 2012;91(12):1110-8.

7. van der Mei HC, White DJ, Kamminga-Rasker HJ, Knight J, Baig AA, Smit J, et al. Influence of dentifrices and dietary components in saliva on wettability of pellicle-coated enamel in vitro and in vivo. Eur J Oral Sci 2002;110:434-8.

8. Vitorino R, Calheiros-Lobo MJ, Duarte JA, Domingues PM, Amado FM. Peptide profile of human acquired enamel pellicle using MALDI tandem MS. J Sep Sci 2008; 31(3): 523–37.

9. Ko?cielniak D, Jurczak A, Zygmunt A, Krzy?ciak W. Salivary proteins in health and disease. Acta Biochim Pol. 2012;59 (4):451-7.

10. Hemadi AS, Huang R, Zhou Y, Zou J. Salivary proteins and microbiota as biomarkers for early childhood caries risk assessment. Int J Oral Sci 2017;9(11):e1.

11. Lindén SK, Wickström C, Lindell G, Gilshenan K, Carlstedt I. Four modes of adhesion are used during Helicobacter pylori binding to human mucins in the oral and gastric niches. Helicobacter. 2008;13(2):81-93.

12. Frenkel ES, Ribbeck K. Salivary mucins in host defense and disease prevention. J Oral Microbiol. 2015: 7:29759.

13. Salvatori O, Puri S, Tati S, Edgerton M. Innate Immunity and Saliva in Candida albicans-mediated Oral Diseases. J Dent Res 2016;95(4):365-71.

14. Carlson DM, Zhou J, Wright PS. Molecular Structure and Transcriptional Regulation of the Salivary Gland Proline Rich Protein Multigene Families. Prog. Nucleic Acid Res. Mol Biol 1991;41:1-22.

15. Mehansho H, Hagerman A, Clements S, Butler L, Rogler J, Carlson DM. Modulation of Proline-Rich Protein Biosynthesis in Rat Parotid Glands by Sorghums with High Tannin Levels. Proc. Natl. Acad. Sci. U.S.A. 80:3948-3952 (1983).

16. Nagler RM. Ionizing irradiation and the salivary gland sequelae. Biomed Rev 1998;9:121–9.

17. Deimling D, Breschi L, Hoth-Hannig W, Ruggeri A, Hannig C, Nekrashevych Y, et al. Electron microscopic detection of ?-amylase in the in situ formed pellicle. Eur J Oral Sci 2004;112:503-9.

18. Carlen A, Borjesson AC, Nikdel K, Olsson J. Composition of pellicles formed in vivo on tooth surfaces in different parts of the dentition, and in vitro on hydroxyapatite. Caries Res1998;32:447–55.

19. Scannapieco FA, Torres GI, Levine MJ. Salivary amylase pro-motes adhesion of oral streptococci to hydroxyapatite. J DentRes 1995;74:1360–6.

20. Hannig C, AttinT, HannigM, HenzeE, BrinkmannK, ZechR. Immobilisation and activity of human ?-amylase in the acquired enamel pellicle. Arch Oral Biol 2004; 49: 469-78.

21. Nikitkova AE, Haase EM, Scannapieco FA. Taking the starch out of oral biofilm formation: molecular basis and functional significance of salivary ?-amylase binding to oral streptococci. Appl Environ Microbiol 2013;79(2):416-23.

22. Kandra L, GyemantG, ZajaczA, BattaG. Inhibitory effects of tannin on human salivary ?-amylase. Biochem Biophys Res Commun. 2004;319(4):1265-71.

23. Brandtzaeg P. Secretory IgA: Designed for Anti-Microbial Defense. Front Immunol. 2013;4:222.

24. Bikker FJ, Cukkemane N, Nazmi K, Veerman EC. Identification of the hydroxyapatite-binding domain of salivary agglutinin. Eur J Oral Sci 2013;121:7-12.

25. Stenudd C, Nordlund A, Ryberg M, Johansson I, Källestål C, Strömberg N. The association of bacterial adhesion with dental caries. J Dent Res 2001;80:2005-10.

26. Chapple DS, Hussain R, Joannou CL, Hancock RE, Odell E, Evans RW, et al. Structure and association of human lactoferrin peptides with Escherichia coli lipopolysaccharide. Antimicrob Agents Chemother 2004; 48(6):2190-8.

27. Rosenfeld Y, Papo N, Shai Y. Endotoxin (lipopolysaccharide) neutralization by innateimmunity host-defense peptides. Peptide properties and plausible modes of action. J Biol Chem 2006; 281(3):1636-43.

28. Dickinson DP. Salivary (SD-type) cystatins: over one billion years in the making—but to what purpose? Crit Rev Oral Biol Med 2002;13(6):485-508.

29. Kim JT, Lee SJ, Kang MA, Park JE, Kim B-Y, Yoon D-Y, et al. Cystatin SN neutralizes the inhibitory effect of cystatin C on cathepsin B activity. Cell Death Dis 2013;4(12):e974.

30. Lynge Pedersen AM, Belstrøm D. The role of natural salivary defences in maintaining a healthy oral microbiota. J Dent 2019;80 Suppl 1:S3-12.

31. Bechinger B, Gorr SU. Antimicrobial Peptides: Mechanisms of Action and Resistance. J Dent Res 2017;96(3):254-60.

32. Ribeiro TR, Dria KJ, de Carvalho CB, Monteiro AJ, Fonteles MC, de Moraes Carvalho K, Fonteles CS. Salivary peptide profile and its association with early childhood caries. Int J Paediatr Dent 2013;23(3): 225-34.

33. Colombo NH, Ribas L, Pereira JA, Kreling PF, Kressirer CA, Tanner AC, et al. Antimicrobial peptides in saliva of children with severe early childhood caries. Arch Oral Biol 2016;69:40-6.

34. Dale BA, Fredericks LP. Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol 2005; 7(2):119-33.

35. Yin C, Dang HN, Gazor F, Huang GT. Mouse salivary glands and human ?-defensin-2 as a study model for antimicrobial gene therapy: Technical considerations. Int J Antimicrob Agents 2006;28:352–60.

36. Oppenheim FG, Salih E, Siqueira WL, Zhang W, Helmerhorst EJ. Salivary proteome and its genetic polymorphisms. Ann N Y Acad Sci 2007;1098:22-50.

37. Inzitari R, Cabras T, Rossetti DV, Fanali C, Vitali A, Pellegrini M, Paludetti G, Manni A, Giardina B, Messana I, Castagnola M. Detection in human saliva of different statherin and P-B fragments and derivatives. Proteomics 2006;6:6370-9.

38. Helmerhorst EJ, Traboulsi G, Salih E, Oppenheim FG. Mass spectrometric identification of key proteolytic cleavage sites in statherin affecting mineral homeostasis and bacterial binding domains. J Proteome Res 2010;9(10):5413-21.

39. Xiao Y, Karttunen M, Jalkanen J, Mussi MC, Liao Y, Grohe B, et al. Hydroxyapatite Growth Inhibition Effect of Pellicle Statherin Peptides. J Dent Res 2015;94(8):1106-12.

40.

41-Vijayaprasad KE, Ravichandra KS, Vasa AA, Suzan S. Relation of salivary calcium, phosphorus and alkaline phosphatase with the incidence of dental caries in children. J Indian Soc Pedod Prev Dent 2010;28(3):156-61.

41. Kaur A, Kwatra KS, Kamboj P. Evaluation of non-microbial salivary caries activity parameters and salivary biochemical indicators in predicting dental caries J Indian Soc Pedod Prev Dent 2012;30(3):212-7.

42. Cardoso AA, Lopes LM, Rodrigues LP, Teixeira JJ, Steiner-Oliveira C, Nobre-Dos-Santos M. Influence of salivary parameters in the caries development in orthodontic patients-an observational clinical study. Int J Paediatr Dent 2017;27(6):540-50.

43. Sun X, Huang X, Tan X, Si Y, Wang X, Chen F, et al. Salivary peptidome profiling for diagnosis of severe early childhood caries. J Transl Med 2016;14(1):240.

44. Singh S, Sharma A, Sood PB, Sood A, Zaidi I, Sinha A. Saliva as a prediction tool for dental caries: An in vivo study. J Oral Biol Craniofac Res 2015;5(2):59-64. 45. Fiehn NE, Oram V, Moe D. Streptococci and activities of sucrases and alpha-amylases in supragingival dental plaque and saliva in three caries activity groups. Acta Odontol Scand 1986;44(1):1-9. 46. Borghi GN, Rodrigues LP, Lopes LM, Parisotto TM, Steiner-Oliveira C, Nobre-Dos-Santos M. Relationship among ? amylase and carbonic anhydrase VI in saliva, visible biofilm, and early childhood caries: a longitudinal study. Int J Paediatr Dent 2017;27(3):174-82.

47. Omar OM, Khattab NM, Rashed LA. Glucosyltransferase B, immunoglobulin A, and caries experience among a group of Egyptian preschool children. J Dent Child (Chic) 2012;79(2):63–8.

48. Shifa S, Muthu MS, Amarlal D, Rathna Prabhu V. Quantitative assessment of IgA levels in the unstimulated whole saliva of caries-free and caries-active children. J Indian Soc Pedodont Prev Dent 2008;26(4):158–61.

49. Bagherian A, Jafarzadeh A, Rezaeian M, Ahmadi S, Rezaity MT. Comparison of the salivary immunoglobulin concentration levels between children with early childhood caries and caries-free children. Iran J Immunol 2008; 5(4): 217–21.

50. Fábián TK, Hermann P, Beck A, Fejérdy P, Fábián G. Salivary defense proteins: their network and role in innate and acquired oral immunity. Int J Mol Sci 2012;13(4):4295–320.

51.Shimotoyodome A, Kobayashi H, Tokimitsu I, Matsukubo T, Takaesu Y. Statherin and histatin 1 reduce parotid saliva-promoted Streptococcus mutans strain MT8148 adhesion to hydroxyapatite surfaces. Caries Res 2006;40(5):403-11.

52. Vitorino R, Lobo MJ, Duarte JR, Ferrer-Correia AJ, Domingues PM, Amado FM. The role of salivary peptides in dental caries. Biomed Chromatogr 2005;19(3):214-22.

53. Garcia Triana B, Delfin Soto O, Lavandero Espina AM, Saldana Bernabeu A. Salivary proteins: structure, function and mechanisms of action. Rev Haban Cienc Méd 2012;11:450-6.

54. Jurczak A, Ko?cielniak D, Papie? M, Vyhouskaya P, Krzy?ciak W. A study on ?-defensin-2 and histatin-5 as a diagnostic marker of early childhood caries progression. Biol Res 2015;48:61.

55. Ao S, Sun X, Shi X, Huang X, Chen F, Zheng S. Longitudinal investigation of salivary proteomic profiles in the development of early childhood caries. J Dent 2017;61:21-7.

56. -da Silva JC, Muniz FWMG, Oballe HJR, Andrades M, Rösing CK, Cavagni J. The effect of periodontal therapy on oxidative stress biomarkers: A systematic review. J Clin Periodontol 2018;45(10):1222-7.

57.

58-Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol 1998;25(2):134-44.

58. Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, Podar M, Leys EJ. Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyro sequencing. ISME J 2012;6(6):1176-85.

59. Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol 2011;38:85-105.

60. Pietiäinen M, Liljestrand JM, Kopra E, Pussinen PJ. Mediators between oral dysbiosis and cardiovascular diseases. Eur J Oral Sci. 2018;126 Suppl 1:26-36.

61. Gheren LW, Cortelli JR, Rodrigues E, Holzhausen M, Saad WA. Periodontal therapy reduces arginase activity in saliva of patients with chronic periodontitis. Clin Oral Investig 2008;12(1):67-72.

62. Nisha KJ, Suresh s, Anilkumar A, Padmanabhan S. MIP-1? and MCP-1 as salivary biomarkers in periodontal disease. Saudi Dent J 2018;30(4):292-8.

63. Gomes AM, Douglas-de-Oliveira DW, Oliveira Costa F. Could the biomarker levels in saliva help distinguish between healthy implants and implants with peri-implant disease? A systematic review. Arch Oral Biol 2018;96:216-22.

64. Holmström SB, Lira-Junior R, Zwicker S, Majster M, Gustafsson A, Åkerman S, et al. MMP-12 and S100s in saliva reflect different aspects of periodontal inflammation. Cytokine 2019;113:155-61.

65. Äyräväinen L, Heikkinen AM, Kuuliala A, Ahola K, Koivuniemi R, Moilanen E, Hämäläinen M, Tervahartiala T, Meurman JH, Leirisalo-Repo M, Sorsa T. Anti-rheumatic medication and salivary MMP-8, a biomarker for periodontal disease. Oral Dis 2018;24(8):1562-71.

66. Morelatto RA, López de Blanc SA. Oral cancer mortality in the province of Cordoba, Argentine Republic in the period 1975-2000. A comparative study with other populations. Med Oral Patol Oral Cir Bucal 2006;11(3):E230-5.

67. Zheng J, Sun L, Yuan W, Xu J, Yu X, Wang F, et al. Clinical value of Naa10p and CEA levels in saliva and serum for diagnosis of oral squamous cell carcinoma. J Oral Pathol Med 2018;47(9):830-5.

68. Amiri Dash Atan N, Koushki M, Rezaei Tavirani M, Ahmadi NA. Protein-Protein Interaction Network Analysis of Salivary Proteomic Data in Oral Cancer Cases. Asian Pac J Cancer Prev 2018;19(6):1639-45.

69. Chan JYK, Zhen G, Agrawal N. The role of tumor DNA as a diagnostic tool for head and neck squamous cell carcinoma. Semin Cancer Biol 2018. pii: S1044-579X(17)30253-5.

70. Shan J, Sun Z, Yang J, Xu J, Shi W, Wu Y, et al. Discovery and preclinical validation of proteomic biomarkers in saliva for early detection of oral squamous cell carcinomas. Oral Dis 2018 doi: 10.1111/odi.1297. Epub ahead of print.

71. Lohavanichbutr P, Zhang Y, Wang P, Gu H, Nagana Gowda GA, Djukovic D, et al. Salivary metabolite profiling distinguishes patients with oral cavity squamous cell carcinoma from normal controls. PLoS One 2018;13(9):e0204249.

72. Jou YJ, Lin CD, Lai CH, Tang CH, Huang SH, Tsai MH, et al. Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages. Clin Chim Acta 2011;412(15-16):1357-65.

73. Al Kawas S, Rahim ZH, Ferguson DB. Potential uses of human salivary protein and peptide analysis in the diagnosis of disease. Arch Oral Biol 2012;57:1-9.

74. -Bustamante G, Ma B, Yakovlev G, Yershova K, Le C, Jensen J, et al. Presence of the Carcinogen N'-Nitrosonornicotine in Saliva of E-cigarette Users. Chem Res Toxicol 2018;31(8):731-8.

75. Humberto JSM, Pavanin JV, Rocha MJAD, Motta ACF. Cytokines, cortisol, and nitric oxide as salivary biomarkers in oral lichen planus: a systematic review. Braz Oral Res 2018;32:e82.

76. Grimaldi M, Palisi A, Rossi G, Stillitano I, Faiella F, Montoro P, et al. Saliva of patients affected by salivary gland tumour: An NMR metabolomics analysis. J Pharm Biomed Anal 2018;160:436-42.

77. Ishikawa S, Sugimoto M, Kitabatake K, Sugano A, Nakamura M, Kaneko M, et al. Identification of salivary metabolomic biomarkers for oral cancer screening. Sci Rep 2016;6:31520.

78. Wang Q, Gao P, Wang X, Duan Y. Investigation and identification of potential biomarkers in human saliva for the early diagnosis of oral squamous cell carcinoma.Clin Chim Acta 2014 1;427:79-85.

79. Hussein AA, Forouzanfar T, Bloemena E, de Visscher J, Brakenhoff RH, Leemans CR, et al. A review of the most promising biomarkers for early diagnosis and prognosis prediction of tongue squamous cell carcinoma. Br J Cancer 2018;119(6):724-36.

80. Melino S, Santone C, Di Nardo P, Sarkar B. Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications. FEBS J 2014;281(3):657-72.

81. Meesala D, Penmetsa GS, Dwarakanath CD, Manyam R. Effect of Initial Periodontal Therapy on Salivary Trefoil Factor (TFF3) in otherwise Healthy Patients with Gingivitis and Chronic Periodontitis. Contemp Clin Dent 2018;9(Suppl 1):S11-S16.

82. Bretz WA, Rosa OP. Emerging technologies for the prevention of dental caries. Are current methods of prevention sufficient for the high risk patient? Int Dent J 2011;61 Suppl 1:29-33.

83. Gudipaneni RK, Kumar RV, GJ, Peddengatagari S, Duddu Y. Short term comparative evaluation of antimicrobial efficacy of tooth paste containing lactoferrin, lysozyme, lactoperoxidase in children with severe early childhood caries: a clinical study. J Clin Diagn Res 2014;8(4):ZC18–20.

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2019-08-24

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