Roles of oxygen radicals and elastase in citric acid-induced airway constriction of guinea-pigs
Research article published in British journal of pharmacology (1999)
Abstract
Antioxidants attenuate noncholinergic airway constriction. To further investigate the relationship between tachykinin-mediated airway constriction and oxygen radicals, we explored citric acid-induced bronchial constriction in 48 young Hartley strain guinea-pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes + citric acid; hexa(sulphobutyl)fullerenes + phosphoramidon + citric acid; dimethylthiourea (DMTU) + citric acid; and DMTU + phosphoramidon + citric acid. Hexa(sulphobutyl)fullerenes and DMTU are scavengers of oxygen radicals while phosphoramidon is an inhibitor of the major degradation enzyme for tachykinins. Animals were anaesthetized, paralyzed, and artificially ventilated. Each animal was given 50 breaths of 4 ml saline or citric acid aerosol. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 (FEV0.1), and maximal expiratory flow at 30% total lung capacity (Vmax30) to evaluate the degree of airway constriction. Citric acid, but not saline, aerosol inhalation caused marked decreases in Crs, FEV0.1 and Vmax30, indicating marked airway constriction. This constriction was significantly attenuated by either hexa(sulphobutyl)fullerenes or by DMTU. In addition, phosphoramidon significantly reversed the attenuating action of hexa(sulphobutyl)fullerenes, but not that of DMTU. Citric acid aerosol inhalation caused increases in both lucigenin- and t-butyl hydroperoxide-initiated chemiluminescence counts, indicating citric acid-induced increase in oxygen radicals and decrease in antioxidants in bronchoalveolar lavage fluid. These alterations were significantly suppressed by either hexa(sulphobutyl)fullerenes or DMTU. An elastase inhibitor eglin-c also significantly attenuated citric acid-induced airway constriction, indicating the contributing role of elastase in this type of constriction. We conclude that both oxygen radicals and elastase play an important role in tachykinin-mediated, citric acid-induced airway constriction.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Antioxidants attenuate noncholinergic airway constriction.
Why This Matters for Hirudotherapy
This animal study investigated the roles of oxygen radicals and elastase in citric acid-induced airway constriction in 48 guinea pigs, using radical scavengers and enzyme inhibitors. Among the agents tested, eglin-c—described in the abstract only as "an elastase inhibitor"—significantly attenuated citric acid-induced airway constriction, supporting the conclusion that elastase plays a contributing role in tachykinin-mediated bronchoconstriction. This finding is of indirect relevance to ASH's domain only if eglin-c is considered in the context of leech-derived bioactive molecules, though the abstract itself provides no leech origin for eglin-c. The study is not a hirudotherapy investigation; eglin-c is used as a research tool compound rather than a therapeutic intervention, the experiments involve guinea pigs, and the focus is airway physiology. The abstract provides no explicit leech connection.
Citation
Roles of oxygen radicals and elastase in citric acid-induced airway constriction of guinea-pigs
Lai YL et al. · British journal of pharmacology, 1999
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