The Effect of Topical Ozonated Aloe vera on VEGF Expression and Microvascular Density in Radiation Dermatitis

Authors

  • Yan Wisnu Prajoko Department of Surgical Oncology, Faculty of Medicine, Universitas Diponegoro, Dr. Kariadi General Hospital, Semarang, Indonesia
  • Davin Rizky Parulian Silalahi Department of Surgical Oncology, Faculty of Medicine, Universitas Diponegoro, Dr. Kariadi General Hospital, Semarang, Indonesia
  • Christina Hari Nawangsih Priharsanti Department of Radiology, Faculty of Medicine, Universitas Diponegoro, Dr. Kariadi General Hospital, Semarang, Indonesia
  • Tommy Supit Department of Surgery, Faculty of Medicine, Universitas Diponegoro, Dr. Kariadi General Hospital, Semarang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.8319

Keywords:

Ozonated Aloe vera, Vascularization, VEGF, Microvascular density, Radiation dermatitis, Wound healing

Abstract

BACKGROUND: Radiation dermatitis is one of the most common side effects of external radiation therapy. Ozonated Aloe vera oil is a novel topical intervention with immunomodulatory properties that have been proven to improve wound healing by promoting fibroblast proliferation and collagen synthesis.

AIM: The purpose of this study was to investigate the effect of topical ozonated A. vera oil application on the vascularization aspect of wound healing in a radiation dermatitis animal model.

METHODS: Thirty-six adult male Sprague Dawley rats were randomized into six groups of equal size (n = 6/group): two control and four intervention groups: Positive control (C1) rats were not given any therapy, and comparative control (C2) rats were given topical hydrocortisone cream 2.5%. Subjects in the P1 group were given non-ozonated A. vera therapy, P2 group was given 300 mg/mL ozonated A. vera, P3 group was given 600 mg/mL ozonated A. vera, and P4 was given 1200 mg/mL ozonated A. vera therapy. Subject termination and histopathological analyses of vascular endothelial growth factor (VEGF) and microvascular density were carried out after 7 treatment days.

RESULTS: Based on Weidner microvascular density scoring system, the least microvascular density was observed in C2, P3, and P4 (2.0 ± 0.0), followed by P1 (2.1 ± 0.1), P2 (2.9 ± 1.5), and C1 (3.0 ± 0.7). Based on immunoreactive immunoreactive score (IRS) VEGF scoring system, the lowest expression of VEGF was observed in group P3 (4.1 ± 1.1), followed by P4 (4.3 ± 0.8), C2 (4.3 ± 1.3), P1 (5.1 ± 1.0), P2 (5.4 ± 0.6), and C1 (6.5 ±1.0). There was a strong positive correlation of VEGF and microvascular density.

CONCLUSION: Topical application of ozonated A. vera to the radiated skin of Sprague Dawley rats reduced VEGF expression and microvascular density. This anti-inflammatory effect may suggest its potential clinical application.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Suresha N, Dandekeri S. A clinico-epidemiological study on radiation induced dermatitis of head and neck malignancy patients at a teritiary care centre in south India. IP Indian J Clin Exp Dermatol. 2019;5(4):327-31. https://doi.org/10.18231/j.ijced.2019.068 DOI: https://doi.org/10.18231/j.ijced.2019.068

Ding J, Guo Y, Li Q, Chen J, Hu P, Liu Q, et al. The incidence of postoperative radiotherapy-induced acute dermatitis in breast cancer and its influencing factors for Chinese women. Onco Targets Ther. 2018;11:1665-70. DOI: https://doi.org/10.2147/OTT.S156066

Hymes SR, Strom EA, Fife C. Radiation dermatitis: Clinical presentation, pathophysiology, and treatment 2006. J Am Acad Dermatol. 2006;54(1):28-46. https://doi.org/10.1016/j.jaad.2005.08.054 PMid:16384753 DOI: https://doi.org/10.1016/j.jaad.2005.08.054

Dilalla V, Chaput G, Williams T, Sultanem K. Radiotherapy side effects: Integrating a survivorship clinical lens to better serve patients. Curr Oncol. 2020;27(2):107-12. https://doi.org/10.3747/co.27.6233 PMid:32489253 DOI: https://doi.org/10.3747/co.27.6233

Iacovelli NA, Galaverni M, Cavallo A, Naimo S, Facchinetti N, Iotti C, et al. Prevention and treatment of radiation-induced acute dermatitis in head and neck cancer patients: A systematic review. Future Oncol. 2018;14(3):291-305. https://doi.org/10.2217/fon-2017-0359 PMid:29153015 DOI: https://doi.org/10.2217/fon-2017-0359

McQuestion M. Evidence-based skin care management in radiation therapy: Clinical update. Semin Oncol Nurs. 2011;27(2):e1-17. https://doi.org/10.1016/j.soncn.2011.02.009 PMid:21514477 DOI: https://doi.org/10.1016/j.soncn.2011.02.009

Salvo N, Barnes E, van Draanen J, Stacey E, Mitera G, Breen D, et al. Prophylaxis and management of acute radiation-induced skin reactions: A systematic review of the literature. Curr Oncol. 2010;17(4):94-112. https://doi.org/10.3747/co.v17i4.493 PMid:20697521 DOI: https://doi.org/10.3747/co.v17i4.493

Wong RKS, Bensadoun RJ, Boers-Doets CB, Bryce J, Chan A, Epstein JB, et al. Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC skin toxicity study Group. Supportive Care in Cancer. 2013;21(10):2933-48. https://doi.org/10.1007/s00520-013-1896-2 PMid:23942595 DOI: https://doi.org/10.1007/s00520-013-1896-2

Haddad P, Amouzgar-Hashemi F, Samsami S, Chinichian S, Oghabian MA. Aloe vera for prevention of radiation-induced dermatitis: A self-controlled clinical trial. Curr Oncol. 2013;20(4):e345-8. https://doi.org/10.3747/co.20.1356 PMid:23904773 DOI: https://doi.org/10.3747/co.20.1356

Liang J, Cui L, Li J, Guan S, Zhang K, Li J. Aloe vera: A medicinal plant used in skin wound healing. Tissue Eng Part B Rev. 2021;27(5):455-74. https://doi.org/10.1089/ten.TEB.2020.0236 PMid:33066720 DOI: https://doi.org/10.1089/ten.teb.2020.0236

Hekmatpou D, Mehrabi F, Rahzani K, Aminiyan A. The effect of aloe vera clinical trials on prevention and healing of skin wound: A systematic review. Iran J Med Sci. 2019;44(1):1-9. PMid:30666070

Zeng J, Lu J. Mechanisms of action involved in ozone-therapy in skin diseases. Int Immunopharmacol. 2018;56:235-41. https://doi.org/10.1016/j.intimp.2018.01.040 PMid:29414657 DOI: https://doi.org/10.1016/j.intimp.2018.01.040

Sagai M, Bocci V. Mechanisms of action involved in ozone therapy: Is healing induced via a mild oxidative stress? Med Gas Res. 2011;1:29. https://doi.org/10.1186/2045-9912-1-29 PMid:22185664 DOI: https://doi.org/10.1186/2045-9912-1-29

Hidayat AT, Arifin MT, Nur M, Muniroh M, Susilaningsih N. Ozonated Aloe vera oil effective increased the number of fibroblasts and collagen thickening in the healing response of full-thickness skin defects. Int J Inflam. 2021;2021:6654343. https://doi.org/10.1155/2021/6654343 PMid:33628417 DOI: https://doi.org/10.1155/2021/6654343

Cancer Institute N. Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017. Available from: https://www. meddra.org [Last accessed on 2022 Jan 27].

Cvetkovic D, Movsas B, Dicker AP, Hanlon AL, Greenberg RE, Chapman JD, et al. Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer. Urology. 2001;57(4):821-5. https://doi.org/10.1016/s0090-4295(00)01044-x PMid:11306422 DOI: https://doi.org/10.1016/S0090-4295(00)01044-X

Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36(2):169-80. https://doi.org/10.1007/BF00666038 PMid:8534865 DOI: https://doi.org/10.1007/BF00666038

Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153(2):347-58. https://doi.org/10.1016/j.jss.2008.04.023 PMid:19027922 DOI: https://doi.org/10.1016/j.jss.2008.04.023

Xie TY, Yan W, Lou J, Chen XY. Effect of ozone on vascular endothelial growth factor (VEGF) and related inflammatory cytokines in rats with diabetic retinopathy. Genet Mol Res. 2016;15:15027558. https://doi.org/10.4238/gmr.15027558 PMid:27323014 DOI: https://doi.org/10.4238/gmr.15027558

Tamba US, Arifin MT, Nur M, Muniroh M, Susilanigsih N. The role of ozonated Aloe vera oil in full-thickness skin defects: Macrophage count and epithelization length parameter. F1000Research. 2020;9:1218. https://doi.org/10.12688/f1000research.25063.1 DOI: https://doi.org/10.12688/f1000research.25063.1

Taşdemir Z, Alkan BA, Albayrak H. Effects of ozone therapy on the early healing period of deepithelialized gingival grafts: A randomized placebo-controlled clinical trial. J Periodontol. 2016;87(6):663-71. https://doi.org/10.1902/jop.2016.150217 PMid:26777769 DOI: https://doi.org/10.1902/jop.2016.150217

Moon EJ, Lee YM, Lee OH, Lee MJ, Lee SK, Chung MH, et al. A novel angiogenic factor derived from Aloe vera gel: β-sitosterol, a plant sterol. Angiogenesis. 1999;3(2):117-23. https://doi.org/10.1023/a:1009058232389 PMid:14517429 DOI: https://doi.org/10.1023/A:1009058232389

Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res. 2006;37(4):425-35. https://doi.org/10.1016/j.arcmed.2005.08.006 PMid:16624639 DOI: https://doi.org/10.1016/j.arcmed.2005.08.006

Chand R, Chandra H, Chandra S, Verma SK. Role of microvessel density and vascular endothelial growth factor in angiogenesis of hematological malignancies. Bone Marrow Res. 2016;2016:5043483. PMid:26998362 DOI: https://doi.org/10.1155/2016/5043483

Pettet GJ, Byrne HM, Mcelwain DL, Norbury J. A model of wound-healing angiogenesis in soft tissue. Math Biosci. 1996;135(1):35-63. https://doi.org/10.1016/0025-5564(96)00044-2 PMid:8755336 DOI: https://doi.org/10.1016/0025-5564(96)00044-2

Downloads

Published

2022-03-14

How to Cite

1.
Prajoko YW, Silalahi DRP, Priharsanti CHN, Supit T. The Effect of Topical Ozonated Aloe vera on VEGF Expression and Microvascular Density in Radiation Dermatitis. Open Access Maced J Med Sci [Internet]. 2022 Mar. 14 [cited 2024 Mar. 5];10(A):493-7. Available from: https://oamjms.eu/index.php/mjms/article/view/8319

Most read articles by the same author(s)