The SH-metabolite I of erdosteine, a mucolytic drug, enhances the inhibitory effect of salbutamol on the respiratory burst of neutrophils.
Reactive oxygen species (ROS) are a common denominator of airway inflammation associated with chronic obstructive pulmonary disease (COPD) and asthma, as well as with less frequent lung diseases such as idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF). The most frequently administered drugs used to treat these diseases are bronchodilators, antioxidant/antiphlogistic agents and mucoactive drugs. The metabolization of the mucoactive drug erdosteine produces an active metabolite (Met I) with a reducing SH group. In addition to its mucolytic action, Met I also has useful antioxidant activity. The various activities of beta 2-agonists include their ability to reduce the respiratory burst of neutrophils and the subsequent release of ROS. beta 2-Agonists and mucoactive drugs may be administered to the same patients during the treatment of lung diseases. The aim of this study was to investigate the ability of Met I to potentiate the activity of salbutamol in inhibiting the in vitro respiratory burst of neutrophils by means of chemiluminescence. The combination of Met I 5 and 10 micrograms/ml with salbutamol 10(-5), 10(-6) and 10(-7) M led to a significant reduction in respiratory bursts when the neutrophils were stimulated with the soluble stimulant N-formyl-methionylleucyl-phenylalanine (fMLP). The combinations of the two drugs that reduced the respiratory bursts when a particulate stimulus (Candida albicans) was used were those containing 10(-5) M of salbutamol. The reasons for this different behavior remain unclear and raise questions about the specific roles, sites and mechanisms of action of the different types of stimulation undergone by the respiratory airways.
Dal Sasso
M
M
Center of Respiratory Pharmacology, Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy.
Bovio
C
C
Culici
M
M
Fonti
E
E
Braga
P C
PC
D000420:Albuterol / Q000494:pharmacology*; D004357:Drug Synergism; D005100:Expectorants / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D013864:Thioglycolates / Q000378:metabolism* / Q000494:pharmacology*; D013876:Thiophenes / Q000378:metabolism* / Q000494:pharmacology*
D005100:Expectorants; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D000420:Albuterol