Potentiated interaction between ineffective doses of budesonide and formoterol to control the inhaled cadmium-induced up-regulation of metalloproteinases and acute pulmonary inflammation in rats.
[en] The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases.
Research center :
FARAH - Fundamental and Applied Research for Animals and Health - ULiège
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Zhang, Wenhui
Zhi, Jianming
Cui, Yongyao
Zhang, Fan
Habyarimana, Jean Belt Adélite ; Université de Liège > Département de sciences fonctionnelles (DSF) > Pharmacologie, pharmacothérapie et toxicologie
Cambier, Carole ; Université de Liège > Département de sciences fonctionnelles (DSF) > Département de sciences fonctionnelles (DSF)
Gustin, Pascal ; Université de Liège > Département de sciences fonctionnelles (DSF) > Pharmacologie, pharmacothérapie et toxicologie
Language :
English
Title :
Potentiated interaction between ineffective doses of budesonide and formoterol to control the inhaled cadmium-induced up-regulation of metalloproteinases and acute pulmonary inflammation in rats.
Publication date :
2014
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, United States - California
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