Pentoxifylline inhibits phosgene-induced lung injury via improving hypoxia

Abstract

Inhalation of high concentrations of phosgene often causes pulmonary edema, which obstructs the airway and causes tissue hypoxia. There is currently no specific antidote. This study was performed to investigate the effect behind pentoxifylline (PTX) treatment for phosgene-induced lung injury in rat models. Rats were exposed to phosgene. The protein levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and occludin proteins in lung tissue were determined. The effect of both prophylactic and therapeutic administration of PTX (50 mg/kg and 100 mg/kg) was evaluated. The lung permeability index and HIF-1α protein level increased, the arterial blood oxygenation index (PaO₂/FIO₂ ratio) and occludin protein level decreased significantly 6 h after phosgene exposure (P < 0.05). PTX exerted protective effects by HIF-1α-VEGF-occludin signaling pathway to some extent. Moreover, prophylactic, but not therapeutic administration of PTX (100 mg/kg), exhibited a significant protective effect. Pretreatment with PTX protected against phosgene-induced lung injury, possibly by inhibiting differential expression of HIF-1α, VEGF, and occludin.

Graphical Abstract

Keywords:

• Phosgene
• lung injury
• hypoxia-inducible factor-1α (HIF-1α)
• vascular endothelial growth factor (VEGF)
• occludin
• pentoxifylline (PTX)

Ethical approval

The experiment protocols were approved by the local animal ethics committee. All applicable international, national, and/or institutional guidelines for the care and use.

Author contributions

XD Zhang, WH Yu, MM Liu, and CX Hai designed/performed most of the investigation, data analysis, and wrote the manuscript; R Liu and H Wu provided pathological assistance; Z Wang contributed to interpretation of the data and analyses. All of the authors have read and approved the manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability statement

The datasets generated and analyzed during the present study are available from the corresponding author on reasonable request.

Additional information

Funding

The work was supported by Grants from a Key Project of the Natural Science Foundation of Shaanxi Province (2014JZ009) and the Project of Military Medical Innovation (16CXZ021).