Toxic oxygen free radicals are believed to play a role in the pathogenesis of a number of respiratory diseases. In particular, pulmonary emphysema may occur because of the oxidative impairment of α1-proteinase inhibitor (α1-PI). We report in vitro data on a new thiol agent, P 1507 [N-5-(thioxo-l-prolyl)-l-cysteine], obtained in a series of experiments designed in view of its therapeutic potential in these clinical conditions. We found that P 1507 at the concentration of 5×10-6M was able to almost fully abolish the PMA-triggered PMN-induced oxidative impairment of α1-PI. Protection may be due to the radical scavenger ability P 1507, that markedly reduced superoxide anion production from PMNs. We also found that P 1507 did not significantly impair other defence mechanisms of PMNs (i.e. phagocytosis, chemotaxis and bactericidal activity). The release of cytokines (TNF-α, IL-6 and IL-8) from monocytes was not altered in the presence of P 1507. We conclude that the compound P 1507 may be considered for treatment of clinical conditions characterized by overload of oxidants, on the basis of its ability in preventing the oxidative damage of α1-PI and of a lack of unwanted inhibitory effects towards defence mechanisms of phagocytes.
- α1-proteinase inhibitor
- Chronic obstructive pulmonary disease
ASJC Scopus subject areas
- Pharmacology (medical)