Airway inflammation in cadmium-exposed rats is associated with pulmonary oxidative stress and emphysema.
The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.
Department for Functional Sciences, B41, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium. nathalie.kirschvink@fundp.ac.be
Nathalie
N
Kirschvink
Nathalie
N
Martin
Laurence
L
Fievez
Nicola
N
Smith
David
D
Marlin
Pascal
P
Gustin
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002104:Cadmium / Q000633:toxicity*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000378:metabolism
D000975:Antioxidants; D002104:Cadmium; D014527:Uric Acid; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D005978:Glutathione; D001205:Ascorbic Acid