Using bosentan to treat paraquat poisoning-induced acute lung injury in rats

PLoS One. 2013 Oct 14;8(10):e75943. doi: 10.1371/journal.pone.0075943. eCollection 2013.

Abstract

Background: Paraquat poisoning is well known for causing multiple organ function failure (MODS) and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning.

Objective: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat.

Method: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning); the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day); and a control group (rats were administered intragastric physiological saline). On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1), endothelin-1 (ET-1), and hydroxyproline (HYP) in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes.

Result: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered.

Conclusion: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / blood
  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / pathology
  • Alveolar Epithelial Cells / drug effects
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / pathology
  • Alveolar Epithelial Cells / ultrastructure
  • Animals
  • Bosentan
  • Disease Models, Animal
  • Endothelin-1 / blood
  • Hydroxyproline / metabolism
  • Male
  • Paraquat / poisoning*
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Transforming Growth Factor beta1 / blood

Substances

  • Endothelin-1
  • Sulfonamides
  • Transforming Growth Factor beta1
  • Paraquat
  • Bosentan
  • Hydroxyproline

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Provience, the project number Y2008C123. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.