title: Anti-inflammatory effects of formoterol and ipratropium bromide against acute cadmium-induced pulmonary inflammation in rats.
abstract: In this study, the anti-inflammatory properties of formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of acute pulmonary inflammation induced by cadmium inhalation. Airway resistance and inflammatory responses, including matrix metalloproteinease-2 (MMP-2) and matrix metalloproteinease-9 (MMP-9) activities, were evaluated. Compared to values obtained in rats exposed to cadmium, pretreatment by bronchodilators administered alone significantly prevented the cadmium-induced increase of airway resistance. Formoterol elicited a significant decrease in total cell number, neutrophil and macrophage counts in bronchoalveolar lavage fluid, whereas ipratropium bromide reduced neutrophil numbers. The two compounds administered alone significantly attenuated the lung lesions associated with parenchyma inflammatory cell influx and congestion observed in the cadmium group. The increased MMP-9 activity was significantly attenuated. Although only formoterol induced a decrease protein concentration in bronchoalveolar lavage fluid, both compounds inhibited the pulmonary edema by reducing wet-to-dry weight ratio which returned to values similar to those recorded in the sham group. All the effects of formoterol on the cadmium-induced inflammatory responses were reversed by propranolol. Similar anti-inflammatory effects were obtained in rats pretreated with ilomastat which showed a significant reduction on inflammatory cell infiltration and MMP-9 activity in bronchoalveolar lavage fluid. Neither synergistic nor additive effects were obtained when the two bronchodilators were administered in combination. In conclusion, formoterol and ipratropium bromide partially protect the lungs against the inflammation by reducing neutrophilic infiltration. This protective effect is associated with reduced MMP-9 activity known to play an important pro-inflammatory role in acute inflammatory process.
authors.affiliation: Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.forename: Laurence
authors.initials: L
authors.lastname: Fievez
authors.forename: Esteban
authors.initials: E
authors.lastname: Cheu
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.forename: Weifang
authors.initials: W
authors.lastname: Rong
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Charles
authors.initials: C
authors.lastname: Advenier
authors.forename: Pascal
authors.initials: P
authors.lastname: Gustin
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002104:Cadmium / Q000633:toxicity*; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D000068759:Formoterol Fumarate; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D009241:Ipratropium / Q000494:pharmacology* / Q000627:therapeutic use; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D018680:Cholinergic Antagonists; D004983:Ethanolamines; D006877:Hydroxamic Acids; D007211:Indoles; D002104:Cadmium; D020782:Matrix Metalloproteinases; D009241:Ipratropium; C119203:ilomastat; D000068759:Formoterol Fumarate