The protective role of endogenous glutathione in carrageenan-induced pleurisy in the rat

In the present study we investigated the protective role of endogenous glut athione, a known free radical scavenger, in rats subjected to carrageenan-i nduced pleurisy. In vivo depletion of endogenous glutathione poets with L-b uthionine-(S,R)-sulfoximine (BSO, 1 g/kg for 24 h, intraperitoneally) enhan ces the carrageenan-induced degree of pleural exudation and polymorphonucle ar leukocyte migration in rats subjected to carrageenan-induced pleurisy. L ung myeloperoxidase activity and lipid peroxidation were significantly incr eased in BSO pretreated rats. However, the inducible nitric oxide (NO) synt hase in lung samples was unaffected by BSO pretreatment. Immunohistochemica l analysis for nitrotyrosine revealed a positive staining in lungs from car rageenan-treated rats, which was massively enhanced by BSO pretreatment. Fu rthermore, in vivo BSO pretreatment significantly increased peroxynitrite f ormation as measured by the oxidation of the fluorescent dye dihydrorhodami ne 123, enhanced the appearance of DNA damage, the decrease in mitochondria l respiration and partially decreased the cellular level of NAD(+) in ex vi vo macrophages harvested from the pleural cavity of rats subjected to carra geenan-induced pleurisy. In vivo treatment with exogenous glutathione (50 m g/kg i.p.) significantly reverts the effects of BSO and exerts anti-inflamm atory effects. Thus, endogenous glutathione plays an important protective r ole against carrageenan-induced local inflammation. (C) 1999 Elsevier Scien ce B.V. All rights reserved.