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Sodium cromoglycate and doxantrazole are oxygen radical scavengers

Dept of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands

CORRESPONDENCE: G. Sadeghi-Hashjin, Dept of Veterinary Basic Sciences, Urmia University, PO Box 641, Urmia, Iran. Fax: 98 4413443442. E-mail: g.sadeghi@mail.urmia.ac.ir

Keywords: alveolar macrophages, chemiluminescence, doxantrazole, oxygen radicals, sodium cromoglycate

Received: January 19, 2002
Accepted May 9, 2002

The effects of two mast cell stabilisers, sodium cromoglycate (SCG) and doxantrazole, on the formation of reactive oxygen species (ROS) were studied. Guinea-pig alveolar macrophages (AMs) generated lucigenin-dependent chemiluminescence (LDCL). This was increased when the cells were stimulated by phorbol myristate acetate (PMA) or zymosan (by 133% and 464%, respectively, in total LDCL over 60 min). SCG decreased PMA-induced LDCL at higher concentrations (10 mM, by 55%) than doxantrazole (1 mM, by 75%). SCG decreased radical production by AMs in response to zymosan in a concentration-dependent manner by 72%. Doxantrazole (0.1–1 mM) diminished total LDCL by 30–80%. In addition, glucose oxidase led to LDCL generation when incubated with glucose in a cell-free medium. This was inhibited by 47–83% in the presence of SCG or doxantrazole. SCG and doxantrazole inhibited the hydrogen peroxide- and peroxynitrite-induced LDCL by 92%. Moreover, these drugs slightly increased the survival rate of the AMs.

It is concluded that doxantrazole- and sodium cromoglycate-inhibited lucigenin-dependent chemiluminescence production by guinea-pig alveolar macrophages is due to a direct scavenging effect on reactive oxygen species. Doxantrazole is 10-times more potent. Mast cell stabilisers may be effective in allergic asthma not only by preventing the allergen-induced mediator release, but also by preventing radical-induced lung damage.

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