Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats

J Invest Surg. 2016;29(1):1-5. doi: 10.3109/08941939.2015.1034898. Epub 2015 Aug 25.

Abstract

Purpose: To determine whether prophylaxis with etanercept, an anti-inflammatory drug, would decrease the severity of lung injury in a neonatal rat model of bronchopulmonary dysplasia (BPD);

Materials and methods: Rat pups were divided into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia + placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung morphology was assessed by alveolar surface area percentage, which is a measure of alveolar size. The severities of lung inflammation and antioxidant capacity were assessed by quantifying tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), malondialdehyde (MDA), and superoxide dismutase (SOD) from lung homogenate;

Results: The percentage of alveolar surface areas were significantly higher in group 3 compared to group 2 (p = .004) and similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was significantly higher in group 2 compared to group 1 and group 3 (p < .05 for both). Lung homogenate SOD activities in group 3 was significantly higher than group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-α and TGF-β in lung homogenate than that in group 2 (p < .05 for both) but similar in both group 1 and group 3;

Conclusion: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.

Keywords: bronchopulmonary dysplasia; etanercept; hyperoxic lung injury; neonatal rats.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Bronchopulmonary Dysplasia / drug therapy*
  • Bronchopulmonary Dysplasia / etiology
  • Disease Models, Animal
  • Etanercept / administration & dosage
  • Etanercept / therapeutic use*
  • Female
  • Humans
  • Hyperoxia / complications*
  • Infant, Newborn
  • Infant, Premature / physiology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / physiopathology
  • Male
  • Malondialdehyde / analysis
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / analysis
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Superoxide Dismutase
  • Etanercept