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A Method for Screening Hypochlorous Acid Scavengers by Inhibition of the Oxidation of 5-Thio-2-Nitrobenzoic Acid: Application Anti-asthmatic Drugs

✍ Scribed by T.L. Ching; J. Dejong; A. Bast


Publisher
Elsevier Science
Year
1994
Tongue
English
Weight
344 KB
Volume
218
Category
Article
ISSN
0003-2697

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✦ Synopsis


Neutrophils use a bactericidal mechanism through the release of the enzyme myeloperoxidase which catalyzes the formation of the powerful oxidant hypochlorous acid (HOCl) from H2O2 and Cl-. HOCl can inactivate alpha 1-antiproteinase (alpha 1-AP) which causes increased proteolytic 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 inhibition of this oxidation by a test compound is a measurement of its HOCl scavenging activity. To illustrate the method we tested some well-known HOCl scavengers such as S-methylated glutathione and oxidized lipoate. Finally several anti-asthmatic drugs such as terbutaline, isoproterenol, salbutamol, cromoglycate, theophylline, and dexamethasone were evaluated. Only the drug terbutaline acted as a HOCl scavenger.