Radiant Defense: Harnessing Boron-Based Gel for Shielding Against Radiation-Induced Dermatitis in Rat Models

Abstract

Objective: Radiation therapy commonly induces dermatitis as a side effect. This study aims to assess the efficacy of a boron-based gel in alleviating radiation-induced dermatitis and explore its potential molecular mechanisms. Methods: Thirty-two rats were divided into four equal groups: control, boron alone, irradiation alone, and irradiation with boron groups. The boron-based gel was applied to the skin area receiving 30 Gy of irradiation, 30 minutes before exposure. The evaluation of radiation-induced dermatitis was conducted using a skin scoring system, alongside the analysis of tissue expression levels of Bax, Bcl-2, and Bcl-xl proteins. Results: In the irradiation with boron group, both the skin scores for radiation-induced dermatitis and the levels of Bax protein were significantly lower compared to the radiotherapy-only group (p<0.001, p<0.05 respectively). Bcl-2 expression was reduced in both the irradiation alone and irradiation with boron groups compared to the control group (p<0.05). Additionally, Bcl-xl expression was lower in the irradiation with boron group compared to the other groups (p<0.05). Conclusion: The application of boron-based gel demonstrates a preferential impact on Bax rather than Bcl-2. Moreover, the use of boron-based gel on the skin effectively reduces radiation-induced dermatitis in rats through a Bax-dependent mechanism.

Keywords

• Apoptosis
• Bax
• Radiation
• Rats

References

1. Rosenthal A, Israilevich R, Moy R. Management of acute radiation dermatitis: A review of the literature and proposal for treatment algorithm. J Am Acad Dermatol. 2019;81(2):558-567. doi:10.1016/j.jaad.2019.02.047
2. Bray FN, Simmons BJ, Wolfson AH, Nouri K. Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy. Dermatol Ther (Heidelb). 2016;6(2):185-206. doi:10.1007/s13555-016-0120-y
3. Delfino S, Brunetti B, Toto V, Persichetti P. Burn after breast reconstruction. Burns. 2008;34(6):873-877. doi:10.1016/j.burns.2007.11.004
4. Richardson BN, Lin J, Buchwald ZS, Bai J. Skin Microbiome and Treatment-Related Skin Toxicities in Patients With Cancer: A Mini-Review. Front Oncol. 2022;12:924849. doi:10.3389/fonc.2022.924849
5. Rübe CE, Freyter BM, Tewary G, Roemer K, Hecht M, Rübe C. Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis. Int J Mol Sci. 2024;25(6):3320. doi:10.3390/ijms25063320
6. Miyake T, Shimada M, Matsumoto Y, Okino A. DNA Damage Response After Ionizing Radiation Exposure in Skin Keratinocytes Derived from Human-Induced Pluripotent Stem Cells. Int J Radiat Oncol Biol Phys. 2019;105(1):193-205. doi:10.1016/j.ijrobp.2019.05.006
7. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023
8. Villegas-Becerril E, Jimenez-Garcia C, Perula-de Torres LA, et al. Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients (the Alantel study). Contemp Clin Trials Commun. 2024;39:101288. doi:10.1016/j.conctc.2024.101288

9. Nielsen FH. Nutritional requirements for boron, silicon, vanadium, nickel, and arsenic: current knowledge and speculation. FASEB J. 1991;5(12):2661-2667
10. Hunt CD. The biochemical effects of physiologic amounts of dietary boron in animal nutrition models. Environ Health Perspect. 1994;102 Suppl 7(Suppl 7):35-43. doi:10.1289/ehp.94102s735
11. Türkez H, Geyikoğlu F, Tatar A, Keleş S, Ozkan A. Effects of some boron compounds on peripheral human blood. Z Naturforsch C J Biosci. 2007;62(11-12):889-896. doi:10.1515/znc-2007-11-1218
12. Hunt CD, Idso JP. Dietary boron as a physiological regulator of normal inflammatory response: a review and current research progress. J Trace Elem Exp Med. 1999; 12(3): 221-233.
13. Garcia-Gonzalez M, Mateo P, Bonilla I. Boron requirement for envelope structure and functionin Anabaena PCC 7119 heterocysts. J Exp Bot. 1991; 42(7): 925-929
14. Benderdour M, Van Bui T, Hess K, Dicko A, Belleville F, Dousset B. Effects of boron derivatives on extracellular matrix formation. J Trace Elem Med Biol. 2000;14(3):168-173. doi:10.1016/S0946-672X(00)80006-1
15. Chebassier N, El Houssein O, Viegas I, Dréno B. In vitro induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression in keratinocytes by boron and manganese. Exp Dermatol. 2004;13(8):484-490. doi:10.1111/j.0906-6705.2004.00197.x
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):239-244. doi:10.1016/S0946-672X(02)80051-7
17. Doğan A, Demirci S, Cağlayan AB, et al. Sodium pentaborate pentahydrate and pluronic containing hydrogel increases cutaneous wound healing in vitro and in vivo. Biol Trace Elem Res. 2014;162(1-3):72-79. doi:10.1007/s12011-014-0104-7
18. Randall K, Coggle JE. Expression of transforming growth factor-beta 1 in mouse skin during the acute phase of radiation damage. Int J Radiat Biol. 1995;68(3):301-309. doi:10.1080/09553009514551231
19. Zu G, Dou Y, Tian Q, Wang H, Zhao W, Li F. Role and mechanism of radiological protection cream in treating radiation dermatitis in rats. J Tradit Chin Med. 2014;34(3):329-337. doi:10.1016/s0254-6272(14)60098-4
20. Ince S, Kucukkurt I, Demirel HH, Acaroz DA, Akbel E, Cigerci IH. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere. 2014;108:197-204. doi:10.1016/j.chemosphere.2014.01.038
21. Aysan E, Idiz UO, Elmas L, Saglam EK, Akgun Z, Yucel SB. Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial. J Invest Surg. 2017;30(3):187-192. doi:10.1080/08941939.2016.1232449
22. Bleicken S, Wagner C, García-Sáez AJ. Mechanistic differences in the membrane activity of Bax and Bcl-xL correlate with their opposing roles in apoptosis. Biophys J. 2013;104(2):421-431. doi:10.1016/j.bpj.2012.12.010
23. Josefsson EC. Platelet intrinsic apoptosis. Thromb Res. 2023;231:206-213. doi:10.1016/j.thromres.2022.11.024
24. Michels J, Kepp O, Senovilla L, et al. Functions of BCL-X L at the Interface between Cell Death and Metabolism. Int J Cell Biol. 2013;2013:705294. doi:10.1155/2013/705294
25. Chi C, Hayashi D, Nemoto M, Nyui M, Urano S, Anzai K. Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays. J Radiat Res. 2011;52(1):32-38. doi:10.1269/jrr.10042
26. Deng Y, Wu X. Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria. Proc Natl Acad Sci U S A. 2000;97(22):12050-12055. doi:10.1073/pnas.97.22.12050
27. Carlsen L, El-Deiry WS. Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents. Int J Mol Sci. 2021;22(21):11828. Published 2021 Oct 31. doi:10.3390/ijms222111828
28. Madonna G, Ullman CD, Gentilcore G, Palmieri G, Ascierto PA. NF-κB as potential target in the treatment of melanoma. J Transl Med. 2012;10:53. Published 2012 Mar 20. doi:10.1186/1479-5876-10-53
29. Goloudina AR, Mazur SJ, Appella E, Garrido C, Demidov ON. Wip1 sensitizes p53-negative tumors to apoptosis by regulating the Bax/Bcl-xL ratio. Cell Cycle. 2012;11(10):1883-1887. doi:10.4161/cc.19901
30. Schneider G, Krämer OH. NFκB/p53 crosstalk-a promising new therapeutic target. Biochim Biophys Acta. 2011;1815(1):90-103. doi:10.1016/j.bbcan.2010.10.003
31. Wang ZX, Yang JS, Pan X, et al. Functional and biological analysis of Bcl-xL expression in human osteosarcoma. Bone. 2010;47(2):445-454. doi:10.1016/j.bone.2010.05.027