Effects of boric acid and potassium metaborate on cytokine levels and redox stress parameters in a wound model infected with methicillin‑resistant <em>Staphylococcus aureus</em>

Celebi,Demet; Taghizadehghalehjoughi,Ali; Baser,Sumeyye; Genc,Sidika; Yilmaz,Aysegul; Yeni,Yesim; Yesilyurt,Fatma; Yildirim,Serkan; Bolat,Ismail; Kordali,Saban; Yilmaz,Ferah; Hacimuftuoglu,Ahmet; Celebi,Ozgur; Margina,Denisa; Nitulescu,George Mihai; Spandidos,Demetrios A.; Tsatsakis,Aristidis

doi:10.3892/mmr.2022.12809

Effects of boric acid and potassium metaborate on cytokine levels and redox stress parameters in a wound model infected with methicillin‑resistant Staphylococcus aureus

Authors:
- Demet Celebi
- Ali Taghizadehghalehjoughi
- Sumeyye Baser
- Sidika Genc
- Aysegul Yilmaz
- Yesim Yeni
- Fatma Yesilyurt
- Serkan Yildirim
- Ismail Bolat
- Saban Kordali
- Ferah Yilmaz
- Ahmet Hacimuftuoglu
- Ozgur Celebi
- Denisa Margina
- George Mihai Nitulescu
- Demetrios A. Spandidos
- Aristidis Tsatsakis
View Affiliations

Affiliations: Department of Microbiology, Faculty of Veterinary Medicine, Ataturk University, 25240 Erzurum, Turkey, Department of Medical Pharmacology, Faculty of Medicine, Seyh Edebali University, 11000 Bilecik, Turkey, Department of Medical Microbiology, Faculty of Medicine, Ataturk University, 25240 Erzurum, Turkey, Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, 25240 Erzurum, Turkey, Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, 25240 Erzurum, Turkey, Department of Plant Protection, Fethiye Faculty of Agriculture, Mugla Sitki Kocman University, 48000 Mugla, Turkey, Department of Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania, Laboratory of Clinical Virology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece, Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
Published online on: August 2, 2022 https://doi.org/10.3892/mmr.2022.12809
Article Number: 294
Copyright: © Celebi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Methicillin‑resistant Staphylococcus aureus (MRSA) infections are usually found in hospital settings and, frequently, in patients with open wounds. One of the most critical virulence factors affecting the severity and recurrence of infections is the biofilm; increasing antibiotic resistance due to biofilm formation has led to the search for alternative compounds to antibiotics. The present study aimed to use boric acid and potassium metaborate against MRSA infection in a fibroblast wound model. For this purpose, a two‑part experiment was designed: First, MRSA strains were used for the test, and both boric acid and potassium metaborate were prepared in microdilution. In the second step, an MRSA wound model was prepared using a fibroblast culture, and treatments with boric acid and potassium metaborate were applied for 24 h. For the evaluation of the effects of treatment, cell viability assay (MTT assay), analysis of redox stress parameters, including total oxidant status and total antioxidant capacity analyses, lactate dehydrogenase analysis and immunohistochemical staining were performed. In addition, IL‑1β and IL‑10 gene expression levels were assayed. According to the results, potassium metaborate was more effective and exhibited a lower toxicity to fibroblast cells compared to boric acid; moreover, potassium metaborate decreased the level of prooxidant species and increased the antioxidant status more effectively than boric acid. The IL‑1β level in the bacteria group was high; however, boric acid and potassium metaborate significantly decreased the expression levels of inflammatory markers, exhibiting the potential to improve the resolution of the lesion. On the whole, the findings of the present study suggest that boric acid and potassium metaborate may be effective on the tested microorganisms.

View Figures

View References

1	Macdonald J and Asiedu K: WAWLC: World alliance for wound and lymphedema care. Wounds. 22:55–59. 2010.PubMed/NCBI
2	Hill KE, Malic S, McKee R, Rennison T, Harding KG, Williams DW and Thomas DW: An in vitro model of chronic wound biofilms to test wound dressings and assess antimicrobial susceptibilities. J Antimicrob Chemother. 65:1195–1206. 2010. View Article : Google Scholar : PubMed/NCBI
3	Yarwood JM and Schlievert PM: Quorum sensing in staphylococcus infections. J Clin Invest. 112:1620–1625. 2003. View Article : Google Scholar
4	Larsen JA and Overstreet J: Pulsed radio frequency energy in the treatment of complex diabetic foot wounds: Two cases. J Wound Ostomy Continence Nurs. 35:523–527. 2008. View Article : Google Scholar : PubMed/NCBI
5	European Committee on Antimicrobial Susceptibility Testing (EUCAST), . Breakpoint tables for interpretation of MICs and zone diameters. Version 12.0. EUCAST; Växjö: 2022, https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_12.0_Breakpoint_Tables.pdfJanuary 1–2022
6	Selim S: Mechanisms of gram-positive vancomycin resistance (Review). Biomed Rep. 16:72022. View Article : Google Scholar : PubMed/NCBI
7	Manandhar S, Singh A, Varma A, Pandey S and Shrivastava N: Biofilm producing clinical staphylococcus aureus isolates augmented prevalence of antibiotic resistant cases in tertiary care hospitals of Nepal. Front Microbiol. 9:27492018. View Article : Google Scholar
8	Malone M, Bjarnsholt T, McBain AJ, James GA, Stoodley P, Leaper D, Tachi M, Schultz G, Swanson T and Wolcott RD: The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data. J Wound Care. 26:20–25. 2017. View Article : Google Scholar : PubMed/NCBI
9	Moormeier DE and Bayles KW: Staphylococcus aureus biofilm: A complex developmental organism. Mol Microbiol. 104:365–376. 2017. View Article : Google Scholar
10	Irschik H, Schummer D, Gerth K, Höfle G and Reichenbach H: The tartrolons, new boron-containing antibiotics from a myxobacterium, Sorangium cellulosum. J Antibiot (Tokyo). 48:26–30. 1995. View Article : Google Scholar : PubMed/NCBI
11	Soriano-Ursúa MA, Das BC and TrujILlo-Ferrara JG: Boron-containing compounds: Chemico-biological properties and expanding medicinal potential in prevention, diagnosis and therapy. Expert Opin Ther Pat. 24:485–500. 2014. View Article : Google Scholar
12	Field MC, Horn D, Fairlamb AH, Ferguson MA, Gray DW, Read KD, De Rycker M, Torrie LS, Wyatt PG, Wyllie S and Gilbert IH: Anti-trypanosomatid drug discovery: An ongoing challenge and a continuing need. Nat Rev Microbiol. 15:217–231. 2017. View Article : Google Scholar
13	Wall RJ, Rico E, Lukac I, Zuccotto F, Elg S, Gilbert IH, Freund Y, Alley MR, Field MC, Wyllie S and Horn D: Clinical and veterinary trypanocidal benzoxaboroles target CPSF3. Proc Natl Acad Sci USA. 115:9616–9621. 2018. View Article : Google Scholar : PubMed/NCBI
14	Castanheira M, Huband MD, Mendes RE and Flamm RK: Meropenem-vaborbactam tested against contemporary gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant enterobacteriaceae. Antimicrob Agents Chemother. 61:e00567–17. 2017. View Article : Google Scholar : PubMed/NCBI
15	Yang F, Zhu M, Zhang J and Zhou H: Synthesis of biologically active boron-containing compounds. Medchemcomm. 9:201–211. 2017. View Article : Google Scholar : PubMed/NCBI
16	Das BC, Thapa P, Karki R, Schinke C, Das S, Kambhampati S, Banerjee SK, Van Veldhuizen P, Verma A, Weiss LM and Evans T: Boron chemicals in diagnosis and therapeutics. Future Med Chem. 5:653–676. 2013. View Article : Google Scholar : PubMed/NCBI
17	Jiang L, Zhao YM and Yang MZ: Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells. Oncol Lett. 21:1092021. View Article : Google Scholar
18	Tanaka M and Fujiwara T: Physiological roles and transport mechanisms of boron: Perspectives from plants. Pflugers Arch. 456:671–677. 2008. View Article : Google Scholar : PubMed/NCBI
19	Iavazzo C, Gkegkes ID, Zarkada IM and Falagas ME: Boric acid for recurrent vulvovaginal candidiasis: The clinical evidence. J Womens Health (Larchmt). 20:1245–1255. 2011. View Article : Google Scholar : PubMed/NCBI
20	Borrelly J, Blech MF, Grosdidier G, Martin-Thomas C and Hartemann P: Contribution of a 3% solution of boric acid in the treatment of deep wounds with loss of substance. Ann Chir Plast Esthet. 36:65–9. 1991.(In French).
21	Nzietchueng RM, Dousset B, Franck P, Benderdour M, Nabet P and Hess K: Mechanisms implicated in the effects of boron on wound healing. J Trace Elem Med Biol. 16:239–244. 2002. View Article : Google Scholar
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Valavanidis A, Vlachogianni T and Fiotakis C: 8-hydroxy-2-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxical Rev. 27:120–139. 2009. View Article : Google Scholar
24	Demirci S, Doğan A, Karakuş E, Halıcı Z, Topçu A, Demirci E and Sahin F: Boron and poloxamer (F68 and F127) containing hydrogel formulation for burn wound healing. Biol Trace Elem Res. 168:169–180. 2015. View Article : Google Scholar : PubMed/NCBI
25	National Committee for Clinical Laboratory Standards (NCCLS), . Performance standards for antimicrobial disk susceptibility tests. Approved standard. NCCLS document M2-A5. NCCLS; Villanova, PA: pp. 138–144. 1993
26	O'Toole GA: Classic spotlight: How the gram stain works. J Bacteriol. 198:31282016. View Article : Google Scholar
27	Yilmaz MT: Minimum inhibitory and minimum bactericidal concentrations of boron compounds against several bacterial strains. Turk J Med Sci. 42:1423–1429. 2012.
28	Çomaklı S, Sevim Ç, Kontadakis G, Doğan E, Taghizadehghalehjoughi A, Özkaraca M, Aschner M, Nikolouzakis TK and Tsatsakis A: Acute glufosinate-based herbicide treatment in rats leads to increased ocular interleukin-1β and c-Fos protein levels, as well as intraocular pressure. Toxicol Rep. 6:155–160. 2019. View Article : Google Scholar
29	Kinoshita PF, Yshii LM, Orellana A, Paixão AG, Vasconcelos AR, Lima LS, Kawamoto EM and Scavone C: Alpha 2 Na+, K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells. Sci Rep. 7:48942017. View Article : Google Scholar : PubMed/NCBI
30	Shinde DB, Koratkar SS, Sharma N and Shitole AA: Antioxidant activity and antiproliferative action of methanolic extract of liquorice (Glycyrrhiza Glabra) in Hepg2 cell line. Int J Pharm Pharmaceut Sci. 8:293–298. 2016. View Article : Google Scholar
31	World Health Organization (WHO), . Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics. WHO; Geneva: 2017, https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-neededJuly 5–2022
32	Suci PA, Mittelman MW, Yu FP and Geesey GG: Investigation of ciprofloxacin penetration into pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 38:2125–2133. 1994. View Article : Google Scholar : PubMed/NCBI
33	Rachid S, Ohlsen K, Witte W, Hacker J and Ziebuhr W: Effect of subinhibitory antibiotic concentrations on polysaccharide intercellular adhesin expression in biofilm-forming Staphylococcus epidermidis. Antimicrob Agents Chemother. 44:3357–3363. 2000. View Article : Google Scholar : PubMed/NCBI
34	Ni N, Li M, Wang J and Wang B: Inhibitors and antagonists of bacterial quorum sensing. Med Res Rev. 29:65–124. 2009. View Article : Google Scholar : PubMed/NCBI
35	Sayin Z, Ucan US and Sakmanoglu A: Antibacterial and antibiofilm effects of boron on different bacteria. Biol Trace Elem Res. 173:241–246. 2016. View Article : Google Scholar : PubMed/NCBI
36	Nisha S, Shivamallu AB, Gujjari SK, Shashikumar P, Ali NM and Kulkarni M: Efficacy of preprocedural boric acid mouthrinse in reducing viable bacteria in dental aerosols produced during ultrasonic scaling. Contemp Clin Dent. 12:282–288. 2021. View Article : Google Scholar
37	Martínez SR, Aiassa V, Sola C and Becerra MC: Oxidative stress response in reference and clinical Staphylococcus aureus strains under Linezolid exposure. J Glob Antimicrob Resist. 22:257–262. 2020. View Article : Google Scholar
38	Idiz UO, Aysan E, Firat D, Ercan C, Demirci S and Sahin F: Effects of boric acid-linked ampicillin on the rat intra-abdominal sepsis model. Pak J Pharm Sci. 32:477–481. 2019.
39	Tekeli H, Asıcı GSE and Bildik A: Anti-inflammatory effect of boric acid on cytokines in ovariectomy-induced rats. Cell Mol Biol. 67:313–320. 2022. View Article : Google Scholar
40	Geyikoglu F, Koc K, Erol HS, Colak S, Ayer H, Jama S, Eser G, Dortbudak MB and Saglam YS: The propolis and boric acid can be highly suitable, alone/or as a combinatory approach on ovary ischemia-reperfusion injury. Arch Gynecol Obstet. 300:1405–1412. 2019. View Article : Google Scholar
41	Yu J, Yang Y, Li S and Meng P: Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling. Exp Ther Med. 22:9462021. View Article : Google Scholar : PubMed/NCBI
42	Skaperda Z, Kyriazis D.I, Vardakas P, Tekos F, Antoniou K, Giannakeas N and Kouretas D: In vitro antioxidant properties of herb decoction extracts derived from Epirus, Greece. Int J Funct Nutr. 2:112021. View Article : Google Scholar