Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

J Radiat Res. 2017 Jan;58(1):41-47. doi: 10.1093/jrr/rrw091. Epub 2016 Sep 26.

Abstract

Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway.

Keywords: Smad; TGF-β1; glycyrrhetinic acid; pneumonia; thoracic irradiation.

MeSH terms

  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation / drug effects
  • Glycyrrhetinic Acid / pharmacology
  • Glycyrrhetinic Acid / therapeutic use*
  • Immunohistochemistry
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / drug therapy*
  • Lung Injury / genetics
  • Lung Injury / pathology
  • Mice, Inbred C57BL
  • Radiation Injuries / drug therapy*
  • Radiation Injuries / genetics
  • Radiation Injuries / pathology
  • Smad Proteins / genetics
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Smad Proteins
  • Transforming Growth Factor beta1
  • Glycyrrhetinic Acid