Colchicine protects against hyperoxic lung injury in neonatal rats

Neonatology. 2012;102(4):265-9. doi: 10.1159/000341424. Epub 2012 Aug 22.

Abstract

Background: Bronchopulmonary dysplasia (BPD) is characterized by inflammation, fibrosis and mucosal necrosis, which leads to emphysematous coalescence of alveoli.

Objective: We tested whether prophylaxis with colchicine , an anti-inflammatory, antioxidant and antifibrotic drug, would decrease the severity of lung injury in an animal model of BPD.

Methods: Twenty-five rat pups were divided into three groups: control (n = 8), hyperoxia (n = 7), and hyperoxia + colchicine (n = 10). The hyperoxia groups were exposed to >95% oxygen from day 1 to 10 of life. On day 10, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Lung morphology was assessed by the mean linear intercept (MLI), a measure of alveolar size. The degree of lung inflammation and antioxidant capacity were assessed by quantifying lung homogenate tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels.

Results: Colchicine significantly decreased lung damage as determined by the MLI in the hyperoxia groups (p < 0.01). The median level of lung MDA was significantly higher in the hyperoxia group compared with the control group (p < 0.05) and the colchicine-treated group (p < 0.05). Lung homogenate SOD and GSH-Px activities in the colchicine-treated group were significantly higher than in the hyperoxia group (p < 0.05). Furthermore, colchicine-treated pups had lower lung homogenate TNF-α and IL-1β levels compared with the hyperoxia group (p < 0.05).

Conclusions: Colchicine has favorable effects on alveolarization as well as inflammation and oxidative stress markers in an animal model of BPD.

MeSH terms

  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Animals, Newborn
  • Animals, Suckling
  • Antioxidants / therapeutic use*
  • Colchicine / therapeutic use*
  • Disease Models, Animal
  • Female
  • Glutathione Peroxidase / analysis
  • Glutathione Peroxidase / metabolism
  • Hyperoxia / drug therapy*
  • Hyperoxia / metabolism
  • Hyperoxia / pathology
  • Interleukin-1beta / analysis
  • Interleukin-1beta / metabolism
  • Male
  • Malondialdehyde / analysis
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / analysis
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Colchicine