Ethyl pyruvate alleviates radiation-induced lung injury in mice

Biomed Pharmacother. 2017 Aug;92:468-478. doi: 10.1016/j.biopha.2017.05.111. Epub 2017 May 29.

Abstract

Objective: Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Ethyl pyruvate (EP) was reported to have an ameliorating effect on a variety of systemic inflammation reactions, including acute lung injury. However, the protective effect of EP on RILI has not been explored.

Materials/methods: RILI was induced by a single thoracic irradiation of 16Gy X-rays in C57BL/6 mice. Mice were divided into four groups: control, radiation, 100mg/kg EP, and 200mg/kg dexamethasone. Inflammation and fibrosis grade of lung tissue were scored by H&E and Masson's trichrome staining. Cytokines include IL-1β, IL-6, TNF-α, GM-CSF, M-CSF, TGF-β1, and HMGB1 were measured after irradiation. Colony formation assay was performed to determine the protective effect of EP in RAW264.7 and HBE cells. The effect of EP on HMGB1 was also explored in vitro.

Result: The cytoplasm of bronchial epithelium cells in mice was positive-stained of HMGB1 accompanying with an increase of HMGB1, IL-6, IL-1β, GM-CSF, M-CSF, TNF-α, and TGF-β1 after irradiation. EP prescription significantly reduced pulmonary inflammation infiltration of RILI, along with a decrease of HMGB1, IL-6, IL-1β, and GM-CSF at 4 weeks after irradiation. Furthermore, EP decreased radiation-induced collagen deposition at 20 weeks after irradiation. Pro-fibrotic cytokines including TGF-β1 and HMGB1 in irradiated lung tissue and plasma obviously decreased in EP administration group in the later stage. In vitro, EP administration protected HBE cells from radiation injury. EP also rescued radiation-induced release but not translocation of HMGB1 in RAW264.7 and HBE cells.

Conclusion: EP treatment ameliorates RILI, including radiation-induced fibrosis in mice. The inhibition of production and release of pro-inflammatory or fibrotic cytokines, especially HMGB1, may partly attribute to its attenuating RILI effect.

Keywords: Ethyl pyruvate; HMGB1; Radiation-induced lung injury; TGF-β1.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Animals
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pyruvates / pharmacology
  • Pyruvates / therapeutic use*
  • RAW 264.7 Cells
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology

Substances

  • Inflammation Mediators
  • Pyruvates
  • ethyl pyruvate