Interactions of P 1507, a new antioxidant agent, with phagocyte functions.
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 alpha 1-proteinase inhibitor (alpha 1-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 x 10(-6) M was able to almost fully abolish the PMA-triggered PMN-induced oxidative impairment of alpha 1-PI. Protection may be due to the radical scavenger ability of 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-alpha, 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 alpha 1-PI and of a lack of unwanted inhibitory effects towards defence mechanisms of phagocytes.
Meloni
F
F
Istituto di Tisiologia e Malattie Respiratoire, Università degli Studi di Pavia, IRCCS Policlinico San Matteo, Italy.
Ballabio
P
P
Leo
G
G
Gorrini
M
M
Manzardo
S
S
Coppi
G
G
Luisetti
M
M
D000975:Antioxidants / Q000494:pharmacology*; D002176:Candida albicans / Q000502:physiology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy; D010586:Phagocytes / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D000515:alpha 1-Antitrypsin / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D016207:Cytokines; D004151:Dipeptides; D008070:Lipopolysaccharides; D000515:alpha 1-Antitrypsin; C093441:N-(5-thioxo-L-prolyl)-L-cysteine