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Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells

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Abstract

Purpose

Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model.

Methods

Syrian hamsters, 8–9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression.

Results

TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group (P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa (P < 0.05).

Conclusions

TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients.

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Acknowledgements

This work was supported by the National Defense Medical College Special Research Grant. We would like to thank Dr. Yoshihiro Miyagawa for technical assistance for experiments of western blot analysis.

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, 359-8513, Japan

    D. Kamide, T. Yamashita, K. Araki, M. Tomifuji & A. Shiotani

  2. Department of Otolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan

    T. Yamashita

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  1. D. Kamide
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  2. T. Yamashita
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  3. K. Araki
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  4. M. Tomifuji
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Corresponding author

Correspondence to T. Yamashita.

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Conflict of interest

Authors declare no conflict of interest.

Ethical approval

All procedures involving animals in this study were performed in accordance with the Guidelines for Proper Conduct of Animal Experiments and the US Public Health Service Policy on Human Care and Use of Laboratory Animals and were reviewed and approved by the Animal Ethical Committee of the National Defense Medical College (No. 13075).

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Kamide, D., Yamashita, T., Araki, K. et al. Hangeshashinto (TJ-14) prevents radiation-induced mucositis by suppressing cyclooxygenase-2 expression and chemotaxis of inflammatory cells. Clin Transl Oncol 19, 1329–1336 (2017). https://doi.org/10.1007/s12094-017-1672-8

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  • DOI: https://doi.org/10.1007/s12094-017-1672-8

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