// Jin Hyun Kim 1, 2 , Kyung Mi Kim 3 , Myeong Hee Jung 1 , Jung Hwa Jung 2, 4 , Ki Mun Kang 2, 5 , Bae Kwon Jeong 2, 5 , Jin Pyeong Kim 2, 3 , Jung Je Park 2, 3 , Seung Hoon Woo 2, 3 1 Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea 2 Institute of Health Science, Jinju, Gyeongnam, Republic of Korea 3 Department of Otolaryngology, Jinju, Gyeongnam, Republic of Korea 4 Department of Internal Medicine, Jinju, Gyeongnam, Republic of Korea 5 Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea Correspondence to: Seung Hoon Woo, email: lesaby@hanmail.net Keywords: alpha lipoic acid, salivary gland, radiation, Nox-2, complication Received: December 27, 2015 Accepted: March 16, 2016 Published: April 09, 2016 ABSTRACT Purpose: Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. Results: ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-β1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. Materials and Methods: Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. Conclusions: Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer.