A METHOD FOR SCREENING HYPOCHLOROUS ACID SCAVENGERS BY INHIBITION OF THE OXIDATION OF 5-THIO-2-NITROBENZOIC ACID - APPLICATION ANTIASTHMATIC DRUGS

Neutrophils use a bactericidal mechanism through the release of the en zyme myeloperoxidase which catalyzes the formation of the powerful oxi dant hypochlorous acid (HOCl) from H2O2 and Cl-. HOCl can inactivate a lpha(1)-antiproteinase (alpha(1)-AP) which causes increased proteolyti c activity at sites of pulmonary inflammation. The search for possible HOCl scavengers usually involves time-consuming enzyme assays (e.g., alpha(1)-AP and elastase). We developed a method in which the compound 5-thio-2-nitrobenzoic acid could easily be oxidized by HOCl. The inhi bition of this oxidation by a test compound is a measurement of its HO Cl scavenging activity. To illustrate the method we tested some well-k nown HOCl scavengers such as S-methylated glutathione and oxidized lip oate. Finally several anti-asthmatic drugs such as terbutaline, isopro terenol, salbutamol, cromoglycate, theophylline, and dexamethasone wer e evaluated. Only the drug terbutaline acted as a HOCl scavenger. (C) 1994 Academic Press, Inc.