Neutrophil-associated inflammatory responses in rats are inhibited by phenylarsine oxide

• Published in: European journal of pharmacology 1997-03, Vol.322 (1), p.91-96
• Main Authors: Roussin, Anne, Le Cabec, Véronique, Lonchampt, Michel, De Nadaı̈, Josette, Canet, Emmanuel, Maridonneau-Parini, Isabelle
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-inflammatory drug; Arsenicals; Arsenicals - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Bronchoalveolar Lavage Fluid; Bronchoalveolar Lavage Fluid - cytology; Carrageenan; Cellular Biology; Edema; Edema - chemically induced; Edema - pathology; Edema - prevention & control; Inflammation; Inflammation - metabolism; Inflammation - pathology; Life Sciences; Lipopolysaccharides; Male; Medical sciences; NADPH oxidase; NADPH oxidase inhibitor; Neutrophil; Neutrophils; Neutrophils - physiology; Phagocytes; Phagocytes - drug effects; Phagocytes - metabolism; Pharmacology. Drug treatments; Phenylarsine oxide; Pulmonary Edema; Pulmonary Edema - chemically induced; Pulmonary Edema - pathology; Pulmonary Edema - prevention & control; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species
• ISSN: 0014-2999; 1879-0712; 1879-0712; 0014-2999
• DOI: 10.1016/S0014-2999(96)00988-0

NADPH oxidase is a phagocyte-specific enzyme which produces O 2 − and so initiates a cascade of reactive oxygen species formation. Inflammatory diseases involve overproduction of reactive oxygen species which induce tissue damage. Phenylarsine oxide has been described previously as a complete and direct inhibitor of NADPH oxidase in vitro that acts by covalently binding to vicinal thiol groups of a membrane-associated component of the enzyme. In the present work, the potential anti-inflammatory effect of phenylarsine oxide was tested on two experimental models in rats, carrageenan-induced paw oedema and lipopolysaccharide-mediated lung inflammation. Intraperitoneal injection of phenylarsine oxide reduced (i) reactive oxygen species production by rat phagocytes, (ii) neutrophil infiltration into the lung after inhalation of lipopolysaccharide and (iii) neutrophil-dependent oedema induced by carrageenan in hindpaws. We conclude that phenylarsine oxide has anti-inflammatory properties which are probably exerted by its ability to inhibit neutrophil NADPH oxidase-dependent reactive oxygen species production. The present work provides the basis for the development of new anti-inflammatory, arsenic-free agents reacting at the phenylarsine oxide site, which seems to be the Achilles' heel of NADPH oxidase. © 1997 Elsevier Science B.V. All rights reserved.