The Effects of Low-Power Laser Irradiation on Inflammation and Apoptosis in Submandibular Glands of Diabetes-Induced Rats

PLoS One. 2017 Jan 18;12(1):e0169443. doi: 10.1371/journal.pone.0169443. eCollection 2017.


Diabetes can lead to dysfunction of the secretory capacity in salivary glands. Activation of the receptor for advanced glycation end products (RAGE) and its ligands has been suggested to participate in chronic disorders such as diabetes and its complications. In this study, the expression of RAGE, high mobility group box 1 (HMGB1) and advanced glycation end products (AGE), as well as the effects of low-power laser irradiation (LPLI) in salivary glands of diabetic rats were evaluated, and the mechanisms involved were characterized. The expression of RAGE and HMGB1 at the protein and mRNA levels was observed in submandibular glands (SMGs) of streptozotocin-induced diabetic rats. A diode laser was applied at 660 nm, 70 mW, 20 J/cm2, 0.56 J/point, with a spot area of 0.028 cm2 and its in vivo effects and the pathways involved were evaluated. Immunohistochemistry and western blotting analysis were performed for inflammatory and apoptosis markers. Diabetes up-regulates HMGB1/AGE/RAGE axis gene expression in SMGs that is associated with activation of the nuclear factor kappa B (NF-κB) pathway. Interestingly, LPLI suppresses NF-κB activation induced by inflammation. LPLI also reduces diabetes-induced apoptosis. That effect was accompanied by decreased levels of Bax, and cleaved caspase 3, which were up-regulated in diabetes. Taken together, our data suggest that LPLI reduces diabetes-induced inflammation by reducing the induction of HMGB1, ultimately leading to inhibition of apoptosis in submandibular glands of diabetic rats.

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / pathology
  • Female
  • Glycation End Products, Advanced / metabolism
  • HMGB1 Protein / metabolism
  • Low-Level Light Therapy
  • Rats
  • Rats, Wistar
  • Receptor for Advanced Glycation End Products / metabolism
  • Sialadenitis / metabolism
  • Sialadenitis / pathology
  • Sialadenitis / radiotherapy*
  • Submandibular Gland / pathology
  • Submandibular Gland / radiation effects*


  • Ager protein, rat
  • Glycation End Products, Advanced
  • HMGB1 Protein
  • Hbp1 protein, rat
  • Receptor for Advanced Glycation End Products

Grants and funding

The authors wish to express their gratitude to Dr. Mino Okubo for her help and contributions to this study. They also thank the Brazilian Federal Agency for Support and Evaluation of Graduate Education –CAPES, scholarship process BEX 18807/12-7, and FAPESP, Grant # 2014/21214-1 for financial support. This research was partially supported by the Grant-in-Aid (25462970) for Scientific Research of Ministry of Education, Culture, Sports, Science and Technology, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.