In the present study we investigated the protective role of endogenous
glutathione, a known
free radical scavenger, in rats subjected to
carrageenan-induced
pleurisy. In vivo depletion of endogenous
glutathione pools with L-
buthionine-(S,R)-sulfoximine (BSO, 1 g/kg for 24 h, intraperitoneally) enhances the
carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to
carrageenan-induced
pleurisy. Lung
myeloperoxidase activity and lipid peroxidation were significantly increased in BSO pretreated rats. However, the inducible
nitric oxide (
NO) synthase in lung samples was unaffected by BSO pretreatment. Immunohistochemical analysis for
nitrotyrosine revealed a positive staining in lungs from
carrageenan-treated rats, which was massively enhanced by BSO pretreatment. Furthermore, in vivo BSO pretreatment significantly increased
peroxynitrite formation as measured by the oxidation of the
fluorescent dye dihydrorhodamine 123, enhanced the appearance of DNA damage, the decrease in mitochondrial respiration and partially decreased the cellular level of NAD+ in ex vivo macrophages harvested from the pleural cavity of rats subjected to
carrageenan-induced
pleurisy. In vivo treatment with exogenous
glutathione (50 mg/kg i.p.) significantly reverts the effects of BSO and exerts anti-inflammatory effects. Thus, endogenous
glutathione plays an important protective role against
carrageenan-induced local
inflammation.