Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and emphysema in rats.

Administration, Inhalation; Animals; Body Weight/drug effects; Bronchoalveolar Lavage Fluid/cytology; Cadmium/administration & dosage; Cadmium Poisoning/metabolism/pathology; Emphysema; Lung/metabolism/pathology; Male; Matrix Metalloproteinase 2/biosynthesis; Matrix Metalloproteinase 9/biosynthesis; Metalloproteases;; Pancreatic Elastase/administration & dosage/pharmacology; Plethysmography, Whole Body; Pneumonia/chemically induced/pathology; Pulmonary Emphysema/chemically induced/pathology; Rats; Rats, Sprague-Dawley

Abstract :

[en] This study describes induction of pulmonary inflammation, production of matrix metalloprotease of type 2 (MMP-2) and type 9 (MMP-9), and emphysema in cadmium (Cd)-exposed rats. Sprague-Dawley rats were randomly distributed into two groups: one placebo-exposed group undergoing saline (NaCl 0.9%) inhalation (n=30) and one Cd-exposed group undergoing cadmium (CdCl(2) 0.1%) inhalation (n=30). The animals of the placebo- and Cd-exposed groups were divided in five subgroups (n=6). Subgroups underwent either a single exposure of 1h or repeated exposures three times weekly for 1h during 3 weeks (3W), 5 weeks (5W), 5 weeks followed by 2 weeks without exposure (5W+2) or 5 weeks followed by 4 weeks without exposure (5W+4). Each animal underwent determination of enhanced pause (Penh) as index of airflow limitation prior to the first exposure as well as before sacrifice. The animals were sacrificed the day after their last exposure. The left lung was fixed for histomorphometric analysis (determination of median interwall distance (MIWD)), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. BALF was analyzed cytologically, and MMP-2 and MMP-9 levels were determined by gelatine zymography. Twelve rats previously instilled with pancreatic elastase were used as positive emphysema controls and underwent the same investigations. Cd-exposure induced a significant increase of BALF macrophages, neutrophils and MMP-9 up to 5W+4, whereas MMP-2 gelatinolytic activity returned to baseline levels within 5W. MIWD was significantly increased in all repeatedly Cd-exposed groups and elastase-treated rats. Penh was increased in Cd-exposed rats after a single exposure and after 3W. MMP gelatinolytic activity was significantly correlated with macrophages, neutrophils and Penh. In repeatedly exposed rats, MIWD was positively and significantly correlated with MMP gelatinolytic activity, suggesting that increased MMP-2 and MMP-9 production favours the development of emphysema.

Disciplines :

Cardiovascular & respiratory systems
Biochemistry, biophysics & molecular biology

Author, co-author :

Kirschvink, Nathalie

Vincke, Gregoire

Fievez, Laurence ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire

Onclinx, Cecile

Wirth, Delphine

Belleflamme, Michèle ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie - GIGA-R : Biochimie et biologie moléculaire

Louis, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > Pneumologie-Allergologie

Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.

Peck, Michael J

Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie

Language :

English

Title :

Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and emphysema in rats.

Publication date :

2005

Journal title :

Toxicology

ISSN :

0300-483X

eISSN :

1879-3185

Publisher :

Elsevier, Limerick, Ireland

Volume :

211

Issue :

1-2

Pages :

36-48

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 17 December 2009

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246 (2 by ULiège)

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