Evaluation of the Effect of the Combination of Boron Compounds on Chronic Liver Disease

Abstract

Aim: Enterococcus faecalis has surface adhesion proteins that enable it to attach to human intestinal and vaginal tissue cells with antibiotic-resistant strains in patients. Due to these properties, boron and its derivatives are preferred as therapeutic agents due to their antibacterial, antifungal, antiparasitic and antifungal activities. In this study, we aimed to evaluate the synergistic effect of boron compounds and their effect on biofilms in an infection model created with Enterococcus faecalis 29212 on the HepG2 liver cell line. Materials and Methods: It was determined that sodium perborate monohydrate + zinc borate had the lowest values as a result of the minimum inhibitory concentration and fractional inhibitor concentration studies. It has also been shown that these doses reduce cytotoxic effects. In addition, 32 µg/ml Etidote + 256 µg/ml Sodium Perborate Monohydrate showed the highest biofilm effect. Results: we show that boron compounds effectively reduce biofilm formation and cause the death of bacteria.

Keywords

• Biofilm
• Boron Compounds
• Fractional Inhibition Concentration
• Cell Culture
• Synergistic Effect

Bor Bileşikleri Kombinasyonunun Kronik Karaciğer Hastalığı Üzerindeki Etkisinin Değerlendirilmesi

Abstract

Amaç: Enterococcus faecalis, hastalarda antibiyotiğe dirençli suşlarla insan bağırsak ve vajinal doku hücrelerine bağlanmasını sağlayan yüzey yapışma proteinlerine sahiptir. Bu özelliklerinden dolayı bor ve türevleri antibakteriyel, antifungal, antiparaziter ve antifungal aktivitelerinden dolayı terapötik ajanlar olarak tercih edilmektedir. Bu çalışmada, HepG2 karaciğer hücre hattı üzerinde Enterococcus faecalis 29212 ile oluşturulan bir enfeksiyon modelinde bor bileşiklerinin sinerjistik etkisini ve biyofilmler üzerindeki etkisini değerlendirmeyi amaçladık. Gereç ve Yöntem: Minimum inhibitör konsantrasyonu, fraksiyonel inhibitör konsantrasyonu ve biyofilm çalışmaları ve HepG2 hücre analizleri yapılarak değerlendirildi. Bulgular: Minimum inhibitör konsantrasyonu ve fraksiyonel inhibitör konsantrasyonu çalışmaları sonucunda sodyum perborat monohidrat + çinko boratın en düşük değerlere sahip olduğu belirlendi. Bu dozların sitotoksik etkileri azalttığı da gösterilmiştir. Ayrıca en yüksek biyofilm etkisini 32 µg/ml Etidot + 256 µg/ml Sodyum Perborat Monohidrat göstermiştir. Sonuç: Bor bileşiklerinin biyofilm oluşumunu etkili bir şekilde azalttığını ve bakterilerin ölümüne neden olduğunu gösterdik.

Keywords

• Biyofilm
• Bor Bileşikleri
• Fraksiyonel İnhibisyon Konsantrasyonu
• Hücre Kültürü
• Sinerjik Etki
• Biyofilm, Bor Bileşikleri, Fraksiyonel İnhibisyon Konsantrasyonu, Hücre Kültürü, Sinerjik Etki

References

1. 1. Iida N, Mizukoshi E, Yamashita T, Yutani M, Seishima J, Wang, Z. et al. Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis. Nature cancer. 2021; 2(10):1039–54.
2. 2. Raza T, Ullah S R, Mehmood K, Andleeb S. Vancomycin resistant Enterococci: A brief review. JPMA. The Journal of the Pakis-tan Medical Association. 2018; 68(5): 768–72.
3. 3. Zheng JX, Wu Y, Lin ZW, Pu ZY, Yao WM, Chen Z. Characteristics of and virulence factors associated with biofilm forma-tion in clinical Enterococcus faecalis isolates in China. Front Microbiol. 2017;8:2338.
4. 4. Bowen WH, Burne RA, Wu H, Koo H. Oral biofilms: pathogens, matrix, and polymicrobial interactions in microenviron-ments. Trends Microbiol. 2018;26(3):229-42.
5. 5. Khalifa L, Shlezinger M, Beyth S, Haddad YH, Glazer SC, Beyth N, et al. Phage therapy against Enterococcus faecalis in dental root canals. J Oral Microbiol. 2016;8:32157-67
6. 6. Lei L, Shao M, Yang Y, Mao MY, Yang YM, Hu T. Exopolysaccharide dispelled by calcium hydroxide with volatile vehicles related to bactericidal effect for root canal medication. J Appl Oral Sci. 2016;24(5):487-95.
7. 7. Riboulet E, Verneuil N, La Carbona S, Sauvageot N, Auffray Y, Hartke A, Relationships between oxidative stress response and virulence in Enterococcus faecalis. J Mol Microbiol Biotechnol. 2007;13(1-3):140-6.
8. 8. Baldassarri L, Cecchini R, Bertuccini L. et al. Enterococcus spp. produces slime and survives in rat peritoneal macrophages. Med Microbiol Immunol. 2001;190:113–20.

9. 9. Christensen GD, Baddour LM, Simpson WA. Phenotypic variation of Staphylococcus epidermidis slime production in vitro and in vivo. Infect Immun. 1987;55:2870–7.
10. 10. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002; 15:167–93.
11. 11. Dowidar N, Moesgaard F, Matzen P. Clogging and other complications of endoscopic biliary endoprostheses. Scand J Gast-roenterol. 1991;26:1132–6.
12. 12. Baker SJ, Tomsho JW, Benkovic SJ. Boron-containing inhibitors of synthetases. Chem Soc Rev. 2011; 40:4279–85.
13. 13. Baker SJ, Zhang YK, Akama T, et al. Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis. J Med Chem 2006; 49:4447–50.
14. 14. Akama T, Baker SJ, Zhang YK, et al. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett. 2009; 19:2129–32.
15. 15. Demirci S, Dogan A, Karakus E, Halici Z, Topcu A, Demirci E, et al. Boron and Poloxamer (F68 and F127) Containing Hyd-rogel Formulation for Burn Wound Healing. Biol Trace Elem Res. 2015;168(1):169-80.
16. 16. Nzietchueng RM, Dousset B, Franck P, Benderdour M, Nabet P, Hess K. Mechanisms implicated in the effects of boron on wound healing. J Trace Elem Med Biol. 2002;16(4):239-44
17. 17. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ. et al. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol. 2016;37(11):1288–301.
18. 18. Garcia-Solache M, Rice LB. The Enterococcus: a Model of Adaptability to Its Environment. Clin Microbiol Rev. 2019;32:2.
19. 19. Zasowski EJ, Claeys KC, Lagnf AM, Davis SL, Rybak MJ. Time is of the essence: the impact of delayed antibiotic therapy on patient outcomes in hospital-onset Enterococcal bloodstream infections. Clin Infect Dis. 2016;62:1242–50.
20. 20. Gastmeier P, Schroder C, Behnke M, Meyer E, Geffers C. Dramatic increase in vancomycin-resistant enterococci in Ger-many. J Antimicrob Chemother. 2014;69:1660–4.
21. 21. Scutera S, Zucca M, Savoia D. Novel approaches for the design and discovery of quorum-sensing inhibitors. Expert Opin. Drug Discov. 2014;9:353–66.
22. 22. Shojima A, Nakayama J. Quorum sensing in gram-positive bacteria: Assay protocols for staphylococcal agr and enterococ-cal fsr systems. Methods Mol. Biol. 2014;1147:33–41.
23. 23. Li Y, Ducasse R, Zirah S, Blond A, Goulard C, Lescop E. et al. Characterization of Sviceucin from Streptomyces Provides In-sight into Enzyme Exchangeability and Disulfide Bond Formation in Lasso Peptides. ACS Chem. Biol. 2015;10:2641–9.
24. 24. Nakayama J, Uemura Y, Nishiguchi K, Yoshimura N, Igarashi Y, Sonomoto K. Ambuic acid inhibits the biosynthesis of cyclic peptide quormones in gram-positive bacteria. Antimicrob. Agents Chemother. 2009;53:580–6.
25. 25. Donnelly RF, McCarron PA, Tunney MM, Woolfson AD. Potential of photodynamic therapy in treatment of fungal infections of the mouth. Design and characterization of a mucoadhesive patch containing toluidine blue O. J. Photochem. Photobiol. B Biol. 2007;86:59–69.
26. 26. Justo JA, Bookstaver PB. Antibiotic lock therapy: Review of technique and logistical challenges. Infect. Drug Resist. 2014;7:343–63.
27. 27. Raheem N, Straus SK. Mechanisms of action for antimicrobial peptides with antibacterial and antibiofilm functions. Front. Microbiol. 2019;10:2866.
28. 28. Ruiz-Ruigomez M, Badiola J, Schmidt-Malan SM, Greenwood-Quaintance K, Karau MJ, Brinkman CL. Et al. Direct electrical current reduces bacterial and yeast biofilm formation. Int. J. Bacteriol. 2016;2016:9727810.
29. 29. Carlson RP, Taffs R, Davison WM, Stewart PS. Anti-biofilm properties of chitosan-coated surfaces. J. Biomater. Sci. Polym. Ed. 2008;19:1035–46.
30. 30. Shimizu Y, Ogasawara Y, Matsumoto A, Dairi T. Aplasmomycin and boromycin are specific inhibitors of the futalosine pathway. J Antibiot (Tokyo). 2018;71(11):70.
31. 31. Yılmaz MT. Minimum inhibitory and minimum bac-tericidal concentrations of boron compounds against several bacterial strains. Turk J Med Sci. 2012;42:1423– 9.
32. 32. Akama T, Baker SJ, Zhang YK, et al. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett 2009; 19:2129-32.
33. 33. Sayin Z, Ucan US, Sakmanoglu A. Antibacterial and Antibiofilm Effects of Boron on Different Bacteria. Biological trace element research. 2016;173(1):241–6.