Effect of the mucoactive drug nacystelyn on the respiratory burst of human blood polymorphonuclear neutrophils.
In lung diseases such as chronic obstructive pulmonary disease (COPD) or cystic fibrosis, the activation of phagocytic cells produces high amounts of cytotoxic reactive oxygen species (ROS) that are partly implicated in the pathogenic process. In this study, the ex vivo antioxidant activity of nacystelyn (NAL), a recently developed mucoactive thiol-containing agent, was investigated using the respiratory burst of human blood polymorphonuclear neutrophils (PMNs). The ROS generation was induced by serum-opsonized zymosan and assessed with luminol- and lucigenin-enhanced chemiluminescence (ECL). The activity of NAL was compared with N-acetylcysteine (ACC) and captopril, other thiol-containing pharmacological agents having documented antioxidant properties. The three drugs significantly inhibited the ECL response of activated PMNs in the presence of luminol, a luminogenic agent which mostly reflects the production of hydroxyl and hypohalite radicals. NAL was more efficient than the other two drugs: the concentrations producing a 50% inhibition (IC50) of total luminol-ECL were 290 microM, 1580 microM and 760 microM for NAL, ACC and captopril, respectively. The inhibition of the lucigenin-ECL response of activated PMNs was less marked for all compounds suggesting a poorer reactivity with superoxide radicals. These findings demonstrate that NAL, at concentrations obtainable in vivo by inhalation, impairs the PMNs chemiluminescence response related to hydroxyl and hypohalite radicals production. As those radicals are highly cytotoxic, NAL appears as a promising agent in the prevention of oxidative lung damage caused by an active inflammatory response.
Department of Pharmaceutical Chemistry, Free University of Brussels, Belgium. jneve@resulb.ulb.ac.be
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Nagy
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Vanderbist
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Parij
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Maes
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Fondu
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Nève
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D005100:Expectorants / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects*
D000975:Antioxidants; D005100:Expectorants; C086501:N-acetylcysteine lysinate; D002216:Captopril; D008239:Lysine; D000111:Acetylcysteine