Received 05.09.2022
DOI: 10.35556/idr-2022-4(101)4-11
Experimental microbiological substantiation to the development of domestic preparations of lactoferrin protein for dentistry and maxillofacial surgery
Tsarev V.N.1, Podporin M.S.1, Tsareva T.V.1, Kuznetsova Yu.A.1, Vishlenkova V.V.1, Goldman I.L.2, Sadchikova E.R.2
1 Federal State Budgetary Educational Institution of Higher Education “A.I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
Russia, 127473, Moscow, Delegatskaya St., 20, bld. 1
2 Ministry of Science and Higher Education of the Russian Federation Institute of Gene Biology Russian Academy of Sciences
Russia, 119334, Moscow, Vavilova St, 34/5

E-mail address:

Initial functions of lactoferrin were due to the fact that it is very similar to transferrin, iron binding protein, whose key role in providing iron to developing erythrocytes was already known. Iron is an extremely important element for the development of not only macroorganism, but also microorganisms. The aim of the study was to evaluate the antimicrobial efficacy of the use of various forms of lactoferrin in relation to experimentally modeled polyvid microbial consortia of an odontogenic nature. According to the results of the conducted studies, it was shown that this protein has a pronounced bacteriostatic effect, and has an inhibitory effect against various types of microorganisms with varying degrees of severity. Conclusion. All the samples under study have a clear bacteriostatic effect, and with an increase in the dose, signs of a bactericidal tendency are noted, which allows us to consider them as promising for the creation of dosage forms for dental practice.

Keywords: lactoferrin, automatic cultivation, periodontitis, anaerobes, microbial consortium.

For citation: Tsarev V.N., Podporin M.S., Tsareva T.V., Kuznetsova Yu.A., Vishlenkova V.V., Goldman I.L., Sadchikova E.R. Experimental microbiological substantiation to the development of domestic preparations of lactoferrin protein for dentistry and maxillofacial surgery. Stomatology for All / Int. Dental Review. 2022, no.4(101): 4-11 (In Russian). doi: 10.35556/idr-2022-4(101)4-11
1. Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature. 2017, 543(7643): 15—28.
2. Jentsch H., Sievert Y., Gocke R. Lactoferrin and other markers from gingival crevicular fluid and saliva before and after periodontal treatment. J Clin Periodontol. 2004, 31(7): 511—514.
3. Enigk K., Jentsch H., Rodloff A.C., Eschrich K., Stingu C.-S. Activity of five antimicrobial peptides against periodontal as well as non-periodontal pathogenic strains. J Oral Microbiol. 2020, 12(1): 1829405.
4. Gorr S.-U. Antimicrobial peptides in periodontal innate defense. Front Oral Biol. 2012, 15: 84—98.
5. Talib Н.J., Ahmed M.A. Assessment of salivary lactoferrin and pH levels and their correlation with gingivitis and severity of chronic periodontitis (Part 2). J Bagh Coll Dentistry. 2018, 30(1): 46—52.
6. Aly E., Lopez-Nicolas R., Darwish A.A., Ros-Berruezo G., Frontela-Saseta C. In vitro effectiveness of recombinant human lactoferrin and its hydrolysate in alleviating LPS-induced inflammatory response. Food Res Int. 2019, Apr, 118: 101—107.
7. Gudipaneni R.K., Kumar R.V., 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): 18—20.
8. Shimizu E., Kobayashi T., Wakabayashi H., Yamauchi R., Iwatsuki K., Yoshie H. Effects of orally administered lactoferrin and lactoperoxidase-containing tablets on clinical and bacteriological profiles in chronic periodontitis patients. Intern J Dentistry. 2011, 2011, Article ID 405139, 9 p.
9. Farnaud S., Evans R.W. Lactoferrin: a multifunctional protein with antimicrobial properties. Mol Immunol. 2003, 40(7): 395—405.
10. Ferreira S.M., Goncalves L.S., Torres S.R., Nogueira S.A., Meiller T.F. Lactoferrin levels in gingival crevicular fluid and saliva of HIV-infected patients with chronic periodontitis. J Investig Clin Dent. 2015, 6(1): 16—24.
11. Kothary V., Doster R.S., Rogers L.M., Kirk L.A., Boyd K.L., Romano-Keeler J., Haley K.P., Manning S.D., Aronoff D.M., Gaddy J.A. Group B Streptococcus induces neutrophil recruitment to gestational tissues and elaboration of extracellular traps and nutritional immunity. Front Cell Infect Microbiol. 2017, 7: 19.
12. Halder L.D., Abdelfatah M.A., Jo E.A.H., Jacobsen I.D., Westermann M., Beyersdorf N., Lorkowski S., Zipfel P.F., Skerka C. Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans // Front Immunol. 2017; 7: 671.
13. Wang B., Timilsena Y.P., Blanch E., Adhikari B. Lactoferrin: Structure, function, denaturation and digestion. Crit Rev Food Sci Nutr. 2019, 59(4): 580—596.
14. Bermejo-Pareja F., del Ser T., Valenti M., de la Fuente M., Bartolome F., Carro E. Salivary lactoferrin as biomarker for Alzheimer’s disease: Brain-immunity interactions. Alzheimer’s Dement. 2020, 16: 1196—1204.
15.Tsarev V.N., Makeeva I.M., Sadchikova E.R., Podporin M.S., Trefilova Yu.A., Arzukanyan A.V., Goldman I.L. Methodology for assessing the activity of a poly-functional protein of the transferrin series in experimental modeling of the kinetics of Staphylococcus aureus development. Journal of Microbiology, Epidemiology and Immunobiology. 2021, 6(98): 617—627 (In Russian).
16.Nikolaeva E.N., Tsarev V.N., Ippolitov E.V. Periodontopathogenic bacteria — indicators of the risk of the occurrence and development of periodontitis (part 1). Stomatology for All / International Dental Review. 2011, №3(56): 4—9 (In Russian).
17. Rascon-Cruz Q., Espinoza-Sanchez E.A., Siqueiros-Cendon T.S., Nakamura-Bencomo S.I., Arevalo-Gallegos S., Iglesias-Figueroa B.F. Lactoferrin: A glycoprotein involved in immunomodulation, anticancer, and antimicrobial processes. Molecules. 2021, 26(1): 205.
18. Fernandes K.E., Carter D.A. The antifungal activity of lactoferrin and its derived peptides: Mechanisms of action and synergy with drugs against fungal pathogens. Front Microbiol. 2017, 8: 2.
19. Losse J., Svobodova E., Heyken A., Hube B., Zipfel P.F., Jozsi M. Role of pH-regulated antigen 1 of Candida albicans in the fungal recognition and antifungal response of human neutrophils. Mol Immunol. 2011, 48(15—16): 2135—2143.
20. Takakura N., Wakabayashi H., Ishibashi H., Yamauchi K., Teraguchi S., Tamura Y., Yamaguchi H., Abe S. Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model. J Med Microbiol. 2004, 53: 495—500.
21. Legrand D. Lactoferrin, a key molecule immune and inflammatory processes. Biochem Cell Biol. 2012, 90(3): 252—268.
22. Lu J., Francis J., Doster R.S., Haley K.P., Craft K.M., Moore R.E., Chambers S.A., Aronoff D.M., Osteen K., Damo S.M., Manning S., Townsend S.D., Gaddy J.A. Lactoferrin: A critical mediator of both host immune response and antimicrobial activity in response to Streptococcal infections. ACS Infect Dis. 2020, 6(7): 1615—1623.
23. Gifford J.L., Hunter H.N., Vogel H.J. Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cell Mol Life Sci. 2005, 62(22): 2588—2598.
24. Chernousov A.D., Nikonova M.F., Sharova N.I., Mitin A.N., Litvina M.M., Sadchikov P.E., Goldman I.L., Yarilin A.A., Sadchikova E.R. Neolactoferrin as a stimulator of innate and adaptive immunity. Acta naturae. 2013, 5(4): 78—84 (In Russian).
25. Actor J.K., Hwang S.A., Kruzel M.L. Lactoferrin as a natural immune modulator. Curr Pharm Des. 2009, 15(17): 1956—1973.
26. Damiens E., El Yazidi I., Mazurier J., Elass-Rochard E., Duthille I., Spik G., Boilly-Marer Y. Role of heparan sulphate proteoglycans in the regulation of human lactoferrin binding and activity in the MDA-MB-231 breast cancer cell line. Eur J Cell Biol. 1998, 77(4): 344—351.