Effect of a leukotriene inhibitor (MK886) on nitric oxide and hydrogen peroxide production by macrophages of acutely and chronically stressed mice.

We evaluated the effect of a leukotriene inhibitor (MK886) on nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) production by peritoneal macrophages of mice subjected to acute and chronic stress. Acute stress was induced by keeping mice immobilized in a tube for 2 h. Chronic stress was induced over a 7-day period by the same method, but with increasing duration of immobilization. The effects of MK886 were investigated in-vitro after incubation with peritoneal macrophages, and in-vivo by submitting mice to stress and treating them daily with MK886. Supernatants of macrophage cultures were collected for NO determination and adherent cells were used for H(2)O(2) determination. Macrophages from mice submitted to acute or chronic stress showed no alterations in H(2)O(2) production. However, macrophages of acutely and chronically stressed mice showed inhibition of NO after incubation with MK886 in-vitro. Administration of MK886 to chronically stressed mice increased generation of H(2)O(2) and inhibited production of NO. Our data suggest an important role of leukotrienes in NO synthesis, which is important in controlling replication of several infectious agents, mainly in stressed and immunosuppressed animals.

Effect of Baccharis dracunculifolia D.C. (Asteraceae) extracts and its isolated compounds on macrophage activation.

Baccharis dracunculifolia D.C. (Asteraceae), a shrub which grows wild in Brazil, is the main botanical source of Brazilian green propolis. Since Brazilian propolis shows an immunomodulatory activity, the goal of this work was to evaluate the action of B. dracunculifolia extracts and some of its isolated compounds on reactive oxygen intermediate (H(2)O(2)) production by macrophages obtained from male BALB/c mice. The results showed that the leaf (Bd-L) (25, 50, and 100 microg mL(-1)), leaf rinse (Bd-LR) (25 microg mL(-1)), and the root (Bd-R) (25 microg mL(-1)) extracts enhanced H2O2 release by macrophages. A phytochemical study of the root and leaves of B. dracunculifolia was carried out. The chromatographic fractionation of Bd-R, using several techniques, afforded the isolation of baccharis oxide (1), friedelanol (2), viscidone (11), 11-hydroxy-10,11-dihydro-euparin (12), and 6hydroxy-tremetona (13), while Bd-LR gave the following isolated compounds: baccharis oxide (1), friedelanol (2), isosakuranetin (3), aromadendrin-4'-methyl ether (4), dihydrocumaric acid (5), baccharin (6), hautriwaic acid lactone (7), hautriwaic acid acetate (8), drupanin (9), and cumaric acid (10). Among the isolated compounds, baccharis oxide (1) and friedelanol (2) increased H2O2 production at a concentration of 100 microM. This is the first time that the presence of compounds 7, 8, 12, and 13 in B. dracunculifolia has been reported. Based on these results it is suggested that the crude extracts and some isolated compounds from B. dracunculifolia display an immunomodulatory action.