Dataset Information

Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats.

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 ?-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-?B, I?B-?, and TGF-?1 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.

SUBMITTER: Kim JH

PROVIDER: S-EPMC5045384 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats.

Kim Jin Hyun JH Kim Kyung Mi KM Jung Myeong Hee MH Jung Jung Hwa JH Kang Ki Mun KM Jeong Bae Kwon BK Kim Jin Pyeong JP Park Jung Je JJ Woo Seung Hoon SH

Oncotarget 20160501 20

<h4>Purpose</h4>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.<h4>Results</h4>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 expr ...[more]

PMID: 27072584

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Project description:Cisplatin, a small platinum-containing molecule, is a widely used, highly effective anticancer drug. However, severe side effects have been found in cancer patients treated with cisplatin, including nephrotoxicity, neurotoxicity, and ototoxicity. These cisplatin-induced side effects can have a major impact on patient quality of life, including social development problems in pediatric patients that develop hearing loss. Previous studies have suggested that the major cause of cisplatin-induced ototoxicity is abnormal accumulation of reactive oxygen species (ROS) and oxidative stress. Alpha-lipoic acid (ALA), one of the most effective antioxidants, is known to be involved in the cellular antioxidant system and may have a protective effect on cisplatin-induced ototoxicity. However, the therapeutic effect of ALA on damaged hearing function and its detailed mechanism of action are not fully understood. This study focused on determining whether ALA has a potential as a protective and/or therapeutic agent for cisplatin-induced ototoxicity. Histological and physiological analyses were performed using cisplatin-treated mouse cochlea and HEI-OC1 culture cells in pre- and post-treatment with ALA in vitro and in vivo. We found that ALA contributes to protecting mitochondrial function by preventing ROS accumulation and inhibiting apoptotic cell death. Importantly, post-treatment with ALA consistently showed an almost equal restorative effect to pretreatment, in vitro and in vivo, supporting the possible use of ALA as a therapeutic agent for cisplatin-induced ototoxicity. This study is the first report on a strong therapeutic potential of ALA to rescue ototoxic hearing loss caused by cisplatin, and our data provide key evidence that ALA may act as a reducing agent for glutathione disulfide to increase glutathione levels on behalf of glutathione reductase. This result was consistent in both cultured cells and the mouse model, which improves the clinical value of ALA for therapy of cisplatin-induced ototoxicity.

Dataset Information

Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats.

Purpose

Results

Materials and methods

Conclusions

Publications

Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats.

Similar Datasets

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