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Updated: Jul 31, 2026

Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
[Effect of copper sulphate on the lung damage induced by chronic intermittent exposure to ozone]
Manuel J Oyarzún G1, Susan A Sánchez R1, Nelson Dussaubat D1
1Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile, moyarzun@med.uchile.cl.
Background:
Ozone exposure could increase lung damage induced by airborne particulate matter. Particulate matter lung toxicity has been attributed to its metallic content.
Aim:
To evaluate the acute effect of intratracheal administration of copper sulfate (CuSO4) on rat lungs previously damaged by a chronic intermittent ozone exposure.
Material And Methods:
Two-months-old male Sprague-Dawley rats were exposed to 0.5 ppm ozone four h per day, five days a week, during two months. CuSO4 was intratracheally instilled 20 h after ozone exposure. Controls breathed filtered air or were instilled with 0.9% NaCl or with CuSO4 or were only exposed to ozone. We evaluated lung histopathology. F2 isoprostanes were determined in plasma. Cell count, total proteins, γ glutamyl-transpeptidase (GGT) and alkaline phosphatases (AP) were determined in bronchoalveolar lavage fluid (BALF).
Results:
Ozone increased total cell count, macrophages, proteins and AP in BALF (p < 0.05), and induced pulmonary neutrophil inflammation. CuSO4 plus air increased plasma F2 isoprostane levels and total cell count, neutrophils and proteins in BALF (p < 0.05). Histopathology showed foamy macrophages. Ozone plus CuSO4 exposed animals showed a neutrophil inflammatory lung response and an increase in total cell count, proteins, GGT and AP in BALF (p < 0.05). Foamy and pigmented alveolar macrophages were detected in all lungs of these animals (p < 0.001).
Conclusions:
Intratracheal instillation of a single dose of CuSO4 in rats previously subjected to a chronic and intermittent exposure to ozone induces a neutrophil pulmonary inflammatory response and cytoplasmic damage in macrophages.
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