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.2023 Feb;20(2):516-528.
doi: 10.1111/iwj.13899. Epub 2022 Aug 25.

The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model

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The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model

Yue-Chen Zhao et al. Int Wound J.2023 Feb.

Abstract

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-β in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

Keywords: Vitamin B12; radiation fibrosis; radiation injury; radiodermatitis; radiotherapy.

© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

FIGURE 1
FIGURE 1
The day before the irradiation, the hair was shaved from the tested areas. The skin in the test areas were irradiated with a medical linear accelerator and marked with lines. The four marked areas were divided into drug‐free group, triethanolamine group, Vitamin B12 group and blank control group.
FIGURE 2
FIGURE 2
Skin changes after irradiation. (A) Skin appearance and (B) grade of radiodermatitis with time after irradiation. The observation time points were 0, 4, 6, 8, 10 and 12 weeks. The skin recovery rate of Vitamin B12 group was significantly better than that of other groups.
FIGURE 3
FIGURE 3
Histological changes in the skin in the different groups. (A) H&E staining (×100). (B) Masson staining (×100). (C) Changes in the relative thickness of the epidermis of the skin tissues in each group. *P ˂ .05 (n = 5), **P ˂ .01 (n = 5)
FIGURE 4
FIGURE 4
Detection of protein expression levels in skin tissue in the different groups. (A) COX‐2, detected by immunohistochemistry, (B) NF‐κB, detected by immunohistochemistry, (C) IL‐6, detected by immunohistochemistry, and (D) TGF‐β, detected by immunofluorescence. All magnifications ×100
FIGURE 5
FIGURE 5
Transmission electron micrographs of (A) transverse sections of collagen fibres (×25 000), (B) longitudinal sections of collagen fibres (×15 000), (C) hemidesmosomes (×8000), and (D) tight junctions (×8000). The arrows point to the (C) hemidesmosomes and (D) tight junctions, respectively.
FIGURE 6
FIGURE 6
mRNA expression levels detected by RT‐qPCR in skin tissue in the different groups. (A) COX‐2 (B) NF‐κB (C) IL‐6 (D) TGF‐β. *P ˂ .05 (n = 3), **P ˂ .01 (n = 3)
FIGURE 7
FIGURE 7
Western blot showing COX‐2, NF‐κB, IL‐6, and TGF‐β expression in the different groups. GADPH was used as the loading control.
FIGURE 8
FIGURE 8
(A) Volcano plot and (B) heatmap of significantly different mRNA clusters (Top 50)
FIGURE 9
FIGURE 9
(A) KEGG enrichment scatter plot and (B) GO enrichment bar chart for differentially expressed genes
FIGURE 10
FIGURE 10
GO enrichment‐directed acyclic graph of (A) BP classification, (B) CC classification, and (C) MF classification
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