Alpha lipoic acid attenuates radiation-induced oral mucositis in rats
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Jin Hyun Kim1,2, Myeong Hee Jung1, Jin Pyeong Kim2,3, Hyun-Jung Kim2,4, Jung Hwa Jung2,4, Jong Ryeal Hahm2,4, Ki Mun Kang2,5, Bae-Kwon Jeong2,5 and Seung Hoon Woo2,3,6
1Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea
2Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
3Department of Otolaryngology, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
4Department of Internal Medicine, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
5Department of Radiation Oncology, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
6Beckman Laser Institute, University of California, Irvine, California, USA
Seung Hoon Woo, email: [email protected]
Keywords: alpha lipoic acid, oral mucosa, radiation, Hif-1a, complications
Received: May 05, 2017 Accepted: July 25, 2017 Published: August 16, 2017
Purpose: Radiotherapy is currently one of the main treatment modalities for head and neck cancer; however, it also results in severe toxicity to the normal tissue, to the detriment of patients. This study aimed to investigate whether alpha lipoic acid (ALA) could protect against radiation-induced oral mucositis in a rat model.
Results: On post-irradiation days 4 and 7, the epithelial layer on oral mucosa showed pronounced injury (shortening of the layer) and it is diminished by ALA pretreatment before radiation. Hif-1a expression was significantly induced in the radiation group on days 4, 7, and 28. GLUT1 expression was also induced by radiation at all time points, and the expression levels peaked on day 28. Phosphorylated p53 level was significantly higher in the radiation group on days 4 and 7, and Bax protein expression was significantly higher in the same group on day 4 than ALA-pretreated radiation group. TUNEL-positive staining was significantly lower in the ALA-pretreated radiation group.
Materials and methods: Rats were assigned to one of the following four groups: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation, with the neck area including the oral mucosa evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were sacrificed 4, 7, 28, or 56 days after radiation.
Conclusions: The results show that ALA can be used to ameliorate radiation-induced oral mucositis with head and neck cancer.
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