The Effect of Novel Boron Ester Derivatives on Wound Healing

Yıl 2024, Cilt: 3 Sayı: 3, 33 - 46, 05.12.2024

Arzu Özcan İlçe , Ümmühan Yiğit , Eylem Suveren , Cevher Altuğ , Çetin Boran , Serap Kolukısa , Muhammet Büyükbayram

Öz

Boron's unique physical and chemical characteristics make it possible to create novel boron-containing molecules resulting in a wide range of distinct biological properties. This paves the way for exciting prospects in various scientific disciplines and medical applications through advanced molecular design and research.
In this study, two novel boron-containing molecules were synthesized and their effect on wound healing property were tested in a pilot study as phase 0, in vivo and in vitro in order to test them on a larger sample.
The wound healing percentage of molecule 1 was higher than that of all other groups in terms of wound healing percentage (p = 0.001), and it did not lead to a chronic subcutaneous inflammatory reaction (p<0.05). Collagen production of molecule 1 and molecule 2 on day 7 (p<0.05) and that of molecule 2 on day 14 (p>0.05) were higher.
In this study, obtained boron containing compounds show promising effect on wound healing macroscopically (wound healing percentage) and microscopically (microbiological, histopathological, and immunohistochemical). As a result of the study, 2 patent applications were made.

Anahtar Kelimeler

Wound healing, wound care, boron

Proje Numarası

2018-31-07-15-004.

YENİ BOR ESTER TÜREVLERİNİN YARA İYİLEŞMESİ ÜZERİNDEKİ ETKİSİ

Öz

Bor fiziksel ve kimyasal özellikleri ile yeni biyolojik özelliklere sahip bor içeren moleküller oluşturmayı olanaklı kılar ve moleküler tasarım ile tıbbi uygulamalar yeni alanlarının araştırılması sonucunda insanlığa ve bilim insanlarına fırsatlar sunar.
Bu çalışmada; bir pilot çalışma ile etkinliği göreceli test edilmiş bor içerikli 2 adet sentez molekülün yara iyileşmesine etkisini daha geniş örneklem ile test etmek için faz 0, in vivo, in vitro çalışmalarını gerçekleştirerek yeni ürün geliştirmek amaçlandı.
Yara iyileşme açısından molekül 1'in yara iyileşme yüzdesi diğer tüm gruplardan daha yüksekti (p = 0.001) ve kronik bir cilt altı enflamatuvar reaksiyona yol açmadı (p<0.05). Kolajen üretimi açısından molekül 1’in 7. günde (p<0.05) ve molekül 2'nin 14. günde (p<0.05) kolajen üretimi daha yüksekti.
Bor içerikli sentez içerikli molekülleri, yara iyileşmesini makroskopik (yara iyileşme yüzdesi) ve mikroskopik (mikrobiyolojik, histopatolojik ve immünohistokimyasal) olarak desteklemektedir. Çalışma sonucunda 2 adet patent başvurusu yapılmıştır.

Anahtar Kelimeler

Yara iyileşmesi, yara bakımı, bor

Etik Beyan

Ethical approval for the in vivo experiments was obtained from the Abant Izzet Baysal University Experimental Animal Ethics Board (2019/07).

Destekleyen Kurum

Republic of Turkey Ministry of Energy and Natural Resources, TENMAK Boron Research Institute with the support of project number 2018-31-07-15-004.

Proje Numarası

2018-31-07-15-004.

Kaynakça

• Abbas, A. K., Fausto, N., & Robbins, S. L. (2005). Robbins and Cotran pathologic basis of disease. Saunders.
• Al-Rawi, Z. S., Gorial, F. I., Al-Shammary, W. A., Muhsin, F., Al-Naaimi, A. S., & Kareem, S. (2013). Serum Boron Concentration in Rheumatoid Arthritis: Correlation With Disease Activity, Functional Class, and Rheumatoid Factor. Journal of Experimental & Integrative Medicine, 3(1), 9–15.
• Albaugh, V. L., Mukherjee, K., & Barbul, A. (2017). Proline precursors and collagen synthesis: Biochemical challenges of nutrient supplementation and wound healing. Journal of Nutrition, 147(11), 2011–2017. https://doi.org/10.3945/jn.117.256404
• Alqahtani, M. S., Alqahtani, A., Kazi, M., Ahmad, M. Z., Alahmari, A., Alsenaidy, M. A., & Syed, R. (2020). Wound-healing potential of curcumin loaded lignin nanoparticles. Journal of Drug Delivery Science and Technology, 60(August 2020), 102020. https://doi.org/10.1016/j.jddst.2020.102020
• Altinoz, M. A., Topcu, G., & Elmaci, İ. (2019). Boron’s neurophysiological effects and tumoricidal activity on glioblastoma cells with implications for clinical treatment. International Journal of Neuroscience, 129(10), 963–977. https://doi.org/10.1080/00207454.2019.1595618
• Apdik, H., Doğan, A., Demirci, S., Aydın, S., & Şahin, F. (2015). Dose-dependent Effect of Boric Acid on Myogenic Differentiation of Human Adipose-derived Stem Cells (hADSCs). Biological Trace Element Research, 165(2), 123–130. https://doi.org/10.1007/s12011-015-0253-3
• Avcioglu, F., Behçet, M., Karabork, Ş., & Kurtoglu, M. G. (2019). Antimicrobial Resistance Rates of Microorganisms Isolated from Wound Specimens – Three Year Evaluation. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 9(3), 110–114.
• Aysan, E., Idiz, U. O., Elmas, L., Saglam, E. K., Akgun, Z., & Yucel, S. B. (2017). Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial. Journal of Investigative Surgery, 30(3), 187–192. https://doi.org/10.1080/08941939.2016.1232449
• Benderdour, M., Van Bui, T., Hess, K., Dicko, A., Belleville, F., & Dousset, B. (2000). Effects of boron derivatives on extracellular matrix formation. Journal of Trace Elements in Medicine and Biology, 14(3), 168–173. https://doi.org/10.1016/S0946-672X(00)80006-1
• Borrelly, J., Blech, M. F., Grosdidier, G., Martin-Thomas, C., & Hartemann, P. (1991). Contribution of a 3% solution of boric acid in the treatment of deep wounds with loss of substance. Ann Chir Plast Esthet, 36(1), 65–69.
• Chattopadhyay, S., & Raines, R. T. (2014). Review collagen-based biomaterials for wound healing. Biopolymers, 101(8), 821–833. https://doi.org/10.1002/bip.22486
• Dhivya, S., Padma, V. V., & Santhini, E. (2015). Wound dressings - A review. BioMedicine, 5(4), 24–28. https://doi.org/10.7603/s40681-015-0022-9
• Doğan, A., Demirci, S., Çağlayan, A. B., Kılıç, E., Günay, M. Y., Uslu, Ü., Cumbul, A., & Şahin, F. (2014). Sodium Pentaborate Pentahydrate and Pluronic Containing Hydrogel Increases Cutaneous Wound Healing In Vitro and In Vivo. Biol Trace Elem Res, 1(3), 72–79. https://doi.org/10.1007/s12011-014-0104-7
• Edwards-Jones, V. (2016). Essential microbiology for wound care. Oxford University Press.
• Gupta, A., Kowalczuk, M., Heaselgrave, W., Britland, S. T., Martin, C., & Radecka, I. (2019). The production and application of hydrogels for wound management: A review. European Polymer Journal, 111(September 2018), 134–151. https://doi.org/10.1016/j.eurpolymj.2018.12.019
• Hall, I H, Spielvogel, B. F., Griffin, T. S., Docks, E. L., & Brotherton, R. J. (1989). The effects of boron hypolipidemic agents on LDL and HDL receptor binding and related enzyme activities of rat hepatocytes, aorta cells and human fibroblasts. Research Communications in Chemical Pathology and Pharmacology, 65(3), 297—317. http://europepmc.org/abstract/MED/2554436
• Hall, Iris H, Burnham, B. S., Elkins, A., Spielvogel, B. F., & Sood, A. (1996). Boronated pyrimidines and Purines as Cytotoxic Hypolipidemic and anti-inflamatory agents. Metal _based Drugs, 3(3), 155–160.
• Ince, S., Kucukkurt, I., Cigerci, I. H., Fatih Fidan, A., & Eryavuz, A. (2010). The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. Journal of Trace Elements in Medicine and Biology, 24(3), 161–164. https://doi.org/10.1016/j.jtemb.2010.01.003
• Kurtoğlu, A. H., & Karataş, A. (2009). Current Approaches to Wound Therapy: Modern wound Dressing. J. Fac. Pharm Ankara University, 38(3), 211–232. https://doi.org/10.1501/eczfak_0000000562
• Kuru, R., & Yarat, A. (2017). Boron and a Current Overview of its Effects On Health. 8, 107–114. https://doi.org/10.5152/clinexphealthsci.2017
• Kuzay, H., & İlçe, A. (2023). Determination of Techniques and Methods Given by Caregivers in Chronic Wound Healing and the Knowledge of Caregivers at Home. Journal of Health Care and Rehabilitation, 2(1), 1–9.
• Liu, Y. J., Su, W. T., & Chen, P. H. (2018). Magnesium and zinc borate enhance osteoblastic differentiation of stem cells from human exfoliated deciduous teeth in vitro. Journal of Biomaterials Applications, 32(6), 765–774. https://doi.org/10.1177/0885328217740730
• ohana, S., Kartini, U., Rashid, B., Nasuredin, J., & Kumar, V. (2019). Management and Business Research Quarterly Determinants of Financial Sustainability and Access to Finance among SMEs in Malaysia : A Pilot Study. 10, 1–8. https://doi.org/https://doi.org/10.32038/mbrq.2019
• Metcalfe, A. D., & Ferguson, M. W. J. (2007). Bioengineering skin using mechanisms of regeneration and repair. Biomaterials, 28(34), 5100–5113. https://doi.org/10.1016/j.biomaterials.2007.07.031
• N, T., & P., S. S. J. L. B. A. D. C. F. C. P. S. C. (2019). Films For Clinical Wound Healing Monitoring. World Health Summit, 4–5.
• Penelope, J., Kallis BS, B., & Adam, J. (2018). Collagen Powder in Wound Healing. Journal of Drugs in Dermatology, 17(4), 403–408.
• Racu, M.-V., Scorei, I. R., & Pinzaru, I. (2021). The role of boron in the functioning of the osteoarticular system. The Moldovan Medical Journal, 64(5), 76–80. https://doi.org/10.52418/moldovan-med-j.64-5.21.14
• Ramanathan, G., Muthukumar, T., & Tirichurapalli Sivagnanam, U. (2017). In vivo efficiency of the collagen coated nanofibrous scaffold and their effect on growth factors and pro-inflammatory cytokines in wound healing. European Journal of Pharmacology, 814(April), 45–55. https://doi.org/10.1016/j.ejphar.2017.08.003
• Repertinger, S. K., Campagnaro, E., Fuhrman, J., El-Abaseri, T., Yuspa, S. H., & Hansen, L. A. (2004). EGFR enhances early healing after cutaneous incisional wounding. Journal of Investigative Dermatology, 123(5), 982–989. https://doi.org/10.1111/j.0022-202X.2004.23478.x
• Seneviratne, D., Advani, P., Trifiletti, D. M., Chumsri, S., Beltran, C. J., Bush, A. F., & Vallow, L. A. (2022). Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer. Cancers, 14(12). https://doi.org/10.3390/cancers14123009
• Shrivastav, A., Mishra, A. K., Ali, S. S., Ahmad, A., Abuzinadah, M. F., & Khan, N. A. (2018). In vivo models for assesment of wound healing potential: A systematic review. Wound Medicine, 20(January), 43–53. https://doi.org/10.1016/j.wndm.2018.01.003
• Sood, A., Sood, C. K., Spielvogel, B. F., Hall, I. H., & Wong, O. T. (1992). Synthesis, cytotoxicity, hypolipidemic and anti‐inflammatory activities of amine—boranes and esters of boron analogues of choline and thiocholine. Journal of Pharmaceutical Sciences, 81(5), 458–462. https://doi.org/https://doi.org/10.1002/jps.2600810514
• Temel, H., Atlan, M., Ertas, A., Yener, I., Akdeniz, M., Yazan, Z., Yilmaz, M. A., Doganyigit, Z., Okan, A., & Akyuz, E. (2022). Cream production and biological in vivo/in vitro activity assessment of a novel boron-based compound derived from quercetin and phenyl boronic acid. Journal of Trace Elements in Medicine and Biology, 74(January), 127073. https://doi.org/10.1016/j.jtemb.2022.127073
• Velnar, T., Bailey, T., & Smrkolj, V. (2009). The wound healing process: An overview of the cellular and molecular mechanisms. Journal of International Medical Research, 37(5), 1528–1542. https://doi.org/10.1177/147323000903700531
• Wang, S., Blaha, C., Santos, R., Huynh, T., Hayes, T. R., Beckford-Vera, D. R., Blecha, J. E., Hong, A. S., Fogarty, M., Hope, T. A., Raleigh, D. R., Wilson, D. M., Evans, M. J., Vanbrocklin, H. F., Ozawa, T., & Flavell, R. R. (2019). Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy. Molecular Pharmaceutics, 16(9), 3831–3841. https://doi.org/10.1021/acs.molpharmaceut.9b00464