Pentoxifylline inhibits phosgene-induced lung injury via improving hypoxia

Drug Chem Toxicol. 2023 Nov;46(6):1100-1107. doi: 10.1080/01480545.2022.2131811. Epub 2022 Oct 11.

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.

Keywords: Phosgene; hypoxia-inducible factor-1α (HIF-1α); lung injury; occludin; pentoxifylline (PTX); vascular endothelial growth factor (VEGF).

MeSH terms

  • Animals
  • Hypoxia / chemically induced
  • Hypoxia / drug therapy
  • Lung Diseases*
  • Lung Injury* / chemically induced
  • Lung Injury* / drug therapy
  • Lung Injury* / prevention & control
  • Occludin / genetics
  • Pentoxifylline* / pharmacology
  • Pentoxifylline* / therapeutic use
  • Phosgene* / toxicity
  • Rats
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factors

Substances

  • Pentoxifylline
  • Phosgene
  • Vascular Endothelial Growth Factor A
  • Occludin
  • Vascular Endothelial Growth Factors