SYNTHETIC LACTOFERRIN IN DENTAL DISEASES PREVENTION AND TREATMENT: CURRENT TRENDS AND PERSPECTIVES

Abstract


The current trend in dental science is to develop novel approaches to the treatment of dental diseases. More often the body’s own proteins are being used, as well as lactoferrin that is the component of exocrine glands secretions. At present lactoferrin can be obtained biotechnologically. Lactoferrin is one of the innate immune system components and is a multifunctional glycoprotein from the transferrin family. This protein is capable of iron binding and thus deprives the microbiota of essential microelement. It’s efficacy against Str. mutans, A. actinomycetemcomitans, P. Gingivalis, P. Intermedia, Candida albicans was demonstrated. Lactoferrin is active against cytomegalovirus, herpes simplex virus, human immunodeficiency virus, hepatitis B and C virus. Immunomodulatory possibilities of lactoferrin have been shown. In dentistry recombinant lactoferrin is successfully applied in treatment of periodontal diseases, oral mucosa lesions of bacterial, viral and fungal etiology and also in dental caries prevention.

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About the authors

A. V Shirokova

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

119991, Moscow

A. Yu Turkina

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

119991, Moscow

Yuriy Olegovich Paramonov

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: paramonovy@mail.ru
119991, Moscow
assistant of department clinical dentistry of the I.M. Sechenov First Moscow State Medical University

References

  1. Канышкова Т.Г., Бунева И.Н., Невинский Г.А. Лактоферрин и его биологические функции. Биохимия (Москва). 2001; 66(1): 1-7.
  2. Nuijens J.H., van Berkel P.H., Schanbacher F.L. Structure and biological actions of lactoferrin. J. Mammary Gland Biol. Neoplas. 1996; 1: 285-95.
  3. Valenti P., Antonini G. Lactoferrin: an important host defence against microbial and viral attack. Cell Mol. Life Sci. 2005; 62: 2576-87.
  4. Berlutti F., Pantanella F., Natalizi T., Frioni A., Paesano R., Polimeni A., Valenti P. Antiviral properties of lactoferrin-a natural immunity molecule. Molecules. 2011; 16: 6992-7018. doi: 10.3390/molecules16086992
  5. Wakabayashi H., Kondo I., Kobayashi T., Yamauchi K., Toida T., Iwatsuki K., Yoshie H. Periodontitis, periodontopathic bacteria and lactoferrin. Biometals. 2010; 23: 419-24. doi: 10.1007 / s10534-010-9304-6
  6. Leitch E.C., Willcox M.D. Synergic antistaphylococcal properties of lactoferrin and lysozyme. J. Med. Microbiol. 1998; 47: 837-42.
  7. Naidu S.S., Svensson U., Kishore A.R., Naidu A.S. Relationship between antibacterial activity and porin binding of lactoferrin in Escherichia coli and Salmonella typhimurium. Antimicrob Agents Chemother. 1993; 37(2): 240-5.
  8. Berlutti F., Catizone A., Ricci G., Frioni A., Natalizi T., Valenti P., Polimeni A. Streptococcus mutans and Streptococcus sobrinus are able to adhere and invade human gingival fibroblast cell line. Int. J. Immunopathol. Pharmacol. 2010;23:1253-60.
  9. Velliyagounder K., Alsaedi W., Alabdulmohsen W., Markowitz K., Fine D.H. Oral lactoferrin protects against experimental candidiasis in mice. J. Appl. Microbiol. 2015; 118(1): 212-21. doi: 10.1111/jam.12666.
  10. Wakabayashi H., Uchida K., Yamauchi K., Teraguchi S., Hayasawa H., Yamaguchi H. Lactoferrin given in food facilitates dermatophytosis cure in guinea pig models. J. Antimicrob Chemother. 2000; 46(4): 595-602.
  11. Siqueiros-Cendón T., Arévalo-Gallegos S., Iglesias-Figueroa B.F., García-Montoya I.A., Salazar-Martínez J., Rascón-Cruz Q. Immunomodulatory effects of lactoferrin. Acta Pharmacol. Sin. 2014; 35(5): 557-66. doi: 10.1038/aps.2013.200. Review.
  12. Andersen J.H., Osbakk S.A., Vorland L.H., Traavik T., Gutteberg T.J. Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts. Antiviral Res. 2001; 51(2): 141-9. doi: 10.1016/S0166-3542(01)00146-2.
  13. Siciliano R., Rega B., Marchetti M., Seganti L., Antonini G., Valenti P. Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection. Biochem. Biophys. Res. Commun. 1999; 264:19-23. doi: 10.1006/bbrc.1999.1318.
  14. Berkhout B., Floris R., Recio I., Visser S. The antiviral activity of the milk protein lactoferrin against the human immunodeficiency virus type 1. Biometals. 2004; 17: 291-4. doi: 10.1023/B:BIOM.0000027707.82911.be.
  15. Hara K., Ikeda M., Saito S., Matsumoto S., Numata K., Kato N. Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes. Hepatol. Res. 2002; 24: 228-36. doi: 10.1016/S1386-6346(02)00088-8.
  16. Puddu P., Valenti P., Gessani S. Immunomodulatory effects of lactoferrin on antigen presenting cells. Biochimie. 2009; 91: 11-8. doi: 10.1016/j.biochi.2008.05.005.
  17. Embleton N.D., Berrington J.E., McGuire W., Stewart C.J., Cummings S.P. Lactoferrin: Antimicrobial activity and therapeutic potential. Semin. Fetal Neonat. Med. 2013; 18: 143-9. doi: 10.1016/j.siny.2013.02.001.
  18. Sorimachi K., Akimoto K., Hattori Y., Ieiri T., Niwa A. Activation of macrophages by lactoferrin: secretion of TNF-alpha, IL-8 and NO. Biochem. Mol. Biol. Int. 1997; 43(1): 79-87.
  19. Wang S., Deng Y., Ren J., Xiao B., Chen Z., Tao Z. Lactoferrin administration into the nostril alleviates murine allergic rhinitis and its mechanisms. Scand. J. Immun. 2013; 78: 507-15. doi: 10.1111 / sji.12118.
  20. Berlutti F., Pilloni A., Pietropaoli M., Polimeni A., Valenti P. Lactoferrin and oral diseases: current status and perspective in periodontitis. Ann. Stomatol. (Roma). 2011; 2(3-4): 10-8.
  21. Kaufman D.A. Lactoferrin supplementation to prevent nosocomial infection in preterm infants. JAMA. 2009; 302: 1467-8. doi: 10.1001 / jama.2009.1449
  22. Kang J.F., Li X.L., Zhou R.Y., Li L.H., Feng F.J., Gou X.L. Bioinformatics analysis of lactoferrin gene for several species. Biochem. Genet. 2008; 46: 312-22. doi: 10.1007 / s10528-008-9147-9
  23. Ward P.P., Piddington C.S., Cunningham G.A., Zhou X., Wyatt R.D., et al. A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic. Biotechnology (N Y).1995; 13: 498-503.
  24. Chong D.K., Langridge W.H. Expression of full-length bioactive antimicrobial human lactoferrin in potato plants. Transgenic. Res. 2000; 9: 71-8.
  25. Yang P., Wang J., Gong G., Sun X., Zhang R., Du Z., et al. Cattle Mammary Bioreactor Generated by a Novel Procedure of Transgenic Cloning for Large-Scale Production of Functional Human Lactoferrin. PLoS One. 2008; 3(10): e3453. doi: 10.1371/journal.pone.0003453.
  26. Wang M., Sun Z., Yu T., Ding F., Li L., Wang X., et al. Large-scale production of recombinant human lactoferrin from high-expression, marker-free transgenic cloned cows. Sci. Rep. 2017; 7(1): 10733. doi: 10.1038/s41598-017-11462-z.
  27. van Berkel P.H.C., et al. Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nat. Biotechnol. 2002; 20: 484-7. doi: 10.1038/nbt0502-484
  28. Meyers E.N., Lewandoski M., Martin G.R. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat. Genet. 1998; 18: 136-41. doi: 10.1038/ng0298-136.
  29. Yu H., Chen J., Sun W., Liu S., Zhang A., Xu X., et al. The dominant expression of functional human lactoferrin in transgenic cloned goats using a hybrid lactoferrin expression construct. J. Biotechnol. 2012; 161(3): 198-205. doi: 10.1016/j.jbiotec.2012.06.035.
  30. Черноусов А.Д., Никонова М.Ф., Шарова Н.И., Митин А.Н., Литвина М.М., Садчиков П.Е. и др., Неолактоферрин как стимулятор врожденного и адаптивного иммунитета. Акта Натура. 2013; 5(4): 78-84.
  31. Sachdeva A., Rawat S., Nagpal J. Efficacy of fermented milk and whey proteins in Helicobacter pylori eradication: A review. World J. Gastroenterol. 2014; 20(3): 724-37. doi: 10.3748/wjg.v20.i3.724. Review.
  32. Welsh K.J., Hwang S.A., Boyd S., Kruzel M.L., Hunter R.L., Actor J.K. Influence of Oral Lactoferrin on Mycobacterium tuberculosis induced immunopathology. Tuberculosis (Edinb). 2011; 91 Suppl 1: S105-13. doi: 10.1016/j.tube.2011.10.019.
  33. Actor J.K., Hwang S.A., Kruzel M.L. Lactoferrin as a natural immune modulator. Curr. Pharm. Des. 2009; 15: 1956-73.
  34. Yoo Y.C., Watanabe S., Watanabe R., Hata K., Shimazaki K., Azuma I. Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice. Jpn J. Cancer Res.1997; 88: 184-90.
  35. Cho E., Smith-Warner S.A., Spiegelman D., Beeson W.L., van den Brandt P.A., Colditz G.A., et al. Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J. Natl. Cancer Inst. 2004; 96: 1015-22.
  36. Tsuda H., Sekine K., Nakamura J., Ushida Y., Kuhara T., Takasuka N., et al. Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats. Adv. Exp. Med. Biol. 1998; 443: 273-84.
  37. Wakabayashi H., Yamauchi K., Kobayashi T., Yaeshima T., Iwatsuki K., Yoshie H. Inhibitory Effects of Lactoferrin on Growth and Biofilm Formation of Porphyromonas gingivalis and Prevotella intermedia. Antimicrob Agents Chemother. 2009; 53(8): 3308-16. doi: 10.1128/AAC.01688-08.
  38. Takakura N., Wakabayashi H., Ishibashi H., Teraguchi S., Tamura Y., Yamaguchi H., Abe S. Oral lactoferrin treatment of experimental oral candidiasis in mice. Antimicrob Agents Chemother. 2003; 47: 2619-23.
  39. Velusamy S.K., Fine D.H., Velliyagounder K. Prophylactic effect of human lactoferrin against Streptococcus mutansbacteremia in lactoferrin knockout mice. Microbes Infect. 2014; 16(9): 762-7. doi: 10.1016/j.micinf.2014.07.009.
  40. Velusamy S.K., Markowitz K., Fine D.H., Velliyagounder K. Human lactoferrin protects against Streptococcus mutans-induced caries in mice. Oral Dis. 2016; 22(2): 148-54. doi: 10.1111/odi.12401.
  41. Tenovuo J., Lumikari M., Soukka T. Salivary lysozyme, lactoferrin and peroxidases: antibacterial effects on cariogenic bacteria and clinical applications in preventive dentistry. Proc. Finn. Dent. Soc. 1991; 87(2): 197-208. Review.
  42. Pinheiro S.L., Azenha G.R., Araujo G.S., Puppin Rontani R.M. Effectiveness of casein phosphopeptide-amorphous calcium phosphate and lysozyme, lactoferrin, and lactoperoxidase in reducing Streptococcus mutans counts in dentinal caries. Gen. Dent. 2017; 65(2): 47-50.
  43. Ruhnke M. Epidemiology of Candida albicans infections and role of non-Candida-albicans yeasts. Curr. Drug. Targets. 2006; 7: 495-504.
  44. Kirkpatrick C.H., Green I., Rich R.R., Schade A.L. Inhibition of growth of Candida albicans by iron-unsaturated lactoferrin: relation to host-defense mechanisms in chronic mucocutaneous candidiasis. J. Infect. Dis. 1971; 124: 539-44.
  45. Andres M.T., Viejo-Diaz M., Fierro J.F. Human lactoferrin induces apoptosis-like cell death in Candida albicans: critical role of K+-channel-mediated K+ efflux. Antimicrob Agents Chemother. 2008; 52: 4081-8. doi: 10.1128 / AAC.01597-07
  46. Kuipers M.E., Heegsma J., Bakker H.I., Meijer D.K., Swart P.J., Frijlink E.W., et al. Design and fungicidal activity of mucoadhesive lactoferrin tablets for the treatment of oropharyngeal candidosis. Drug. Deliv. 2002; 9: 31-8.
  47. Masci J.R. Complete response of severe, refractory oral candidiasis to mouthwash containing lactoferrin and lysozyme. Aids. 2000; 14: 2403-4.
  48. 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(6): 391-7.
  49. Gil-Montoya J.A., Guardia-López I., González-Moles M.A. Evaluation of the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lysozyme and lactoferrin in elderly patients with dry mouth-a pilot study. Gerodontology. 2008; 25(1): 3-9. doi: 10.1111/j.1741-2358.2007.00197.x.
  50. Loesche W.J. The antimicrobial treatment of periodontal disease: change the treatment paradigm. Crit. Rev. Oral Biol. Med. 1999; 10: 245-75.
  51. Marsh P.D. Microbiological aspects of the chemical control of plaque and gingivitis. J. Dent. Res. 1992; 71: 1431-8.
  52. Davey M.E., Costerton J.W. Molecular genetics analyses of biofilm formation in oral isolates. Periodontology. 2000. 2006; 42: 13-26.
  53. Alugupalli K.R., Kalfas S. Inhibitory effect of lactoferrin on the adhesion of Actinobacillus actinomycetemcomitans and Prevotella intermedia to fibroblasts and epithelial cells. APMIS. 1995; 103: 154-60.
  54. Aguilera O., Andrés M.T., Heath J., Fierro J.F., Douglas C.W. Evaluation of the antimicrobial effect of lactoferrin on Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens. FEMS Immunol. Med. Microbiol. 1998; 21(1): 29-36.
  55. Kondo I., Kobayashi T., Wakabayashi H., Yamauchi K., Iwatsuki K., Yoshie H. Effects of oral administration of bovine lactoferrin on periodontitis patients. Jpn. J. Conserv. Dent. 2008; 51: 281-91. (In Japanese.) http://wwwsoc.nii.ac.jp/jscd/member/pdf/vol51_no3/291.pdf.
  56. Kalfas S., Andersson M., Edwardsson S., Forsgren A., Naidu A.S. Human lactoferrin binding to Porphyromonas gingivalis, Prevotella intermedia and Prevotella melaninogenica. Oral Microbiol. Immunol. 1991; 6: 350-5.
  57. Velusamy S.K., Poojary R., Ardeshna R., Alabdulmohsen W., Fine D.H., Velliyagounder K. Protective Effects of Human Lactoferrin during Aggregatibacter actinomycetemcomitans-Induced Bacteremia in Lactoferrin-Deficient Mice. Antimicrob Agents Chemother. 2014; 58(1): 397-404. doi: 10.1128/AAC.00020-13.
  58. Baveye S., Elass E., Mazurier J., Spik G., Legrand D. Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process. Clin. Chem. Lab. Med. 1999; 37: 281-6.
  59. Crouch S.P., Slater K.J., Fletcher J. Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood. 1992; 80: 235-40.
  60. Nakano M., Wakabayashi H., Sugahara H., Odamaki T., Yamauchi K., Abe F., et al. Effects of lactoferrin and lactoperoxidase-containing food on the oral microbiota of older individuals. Microbiol. Immunol. 2017; 61(10): 416-26. doi: 10.1111/1348-0421.12537.

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