Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling

Int J Mol Sci. 2019 Nov 13;20(22):5691. doi: 10.3390/ijms20225691.

Abstract

Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient's daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation-induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.

Keywords: alpha-lipoic acid; dry eye syndrome; nfat5; radiation therapy.

MeSH terms

  • Animals
  • Lacrimal Apparatus / drug effects*
  • Lacrimal Apparatus / metabolism
  • Lacrimal Apparatus / pathology
  • Lacrimal Apparatus / radiation effects
  • Male
  • Radiation Injuries / drug therapy*
  • Radiation Injuries / metabolism
  • Radiation Injuries / pathology
  • Radiation-Protective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Thioctic Acid / therapeutic use*
  • Transcription Factors / metabolism*

Substances

  • Nfat5 protein, rat
  • Radiation-Protective Agents
  • Transcription Factors
  • Thioctic Acid