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.
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.
Authors: Jocelyn Dupuis; Martin G Sirois; Eric Rhéaume; Quang T Nguyen; Marie-Élaine Clavet-Lanthier; Genevieve Brand; Teodora Mihalache-Avram; Gabriel Théberge-Julien; Daniel Charpentier; David Rhainds; Paul-Eduard Neagoe; Jean-Claude Tardif Journal: PLoS One Date: 2020-12-02 Impact factor: 3.240