Tl. Ching et al., A METHOD FOR SCREENING HYPOCHLOROUS ACID SCAVENGERS BY INHIBITION OF THE OXIDATION OF 5-THIO-2-NITROBENZOIC ACID - APPLICATION ANTIASTHMATIC DRUGS, Analytical biochemistry, 218(2), 1994, pp. 377-381
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.