The relationship between the anti-inflammatory effects of curcumin and cellular glutathione content in myelomonocytic cells.

Oxidative stress plays an important role during inflammatory diseases and recent therapies have focused on antioxidant administration to diminish oxidative stress and to arrest inflammatory processes. In this study, we investigated the impact of the GSH modulating effects of curcumin, a naturally derived polyphenol, on inflammatory processes in myelomonocytic U937 cells. One hour after administration of 10 micromol/l curcumin reactive oxygen species (ROS) production was significantly increased in undifferentiated U937 cells (+43%). Twenty-four hour after addition of curcumin, a significantly decreased ROS concentration was found (-32%), whereas GSH (+110%) and GSSG (+88%) content increased. A higher concentration of curcumin (25 micromol/l) caused an even stronger increase of GSH (+145%) and GSSG (+101%), but significantly decreased percentage of living cells to 84%. The increased GSH content of differentiated U937 cells after pre-incubation with curcumin was associated with lowered ROS production, nuclear factor kappa B (NFkappaB) activation (-34%) and tumor necrosis factor alpha (TNF-alpha) secretion (-51%) after LPS exposure. Curcumin inhibited TNF-alpha formation was also seen after GSH depletion by buthionine sulfoximine (BSO). This study shows that the antioxidative effects of curcumin are preceded by an oxidative stimulus, which is time and dose-dependent. Excessive concentrations of curcumin may even harm cells, as cell viability was decreased, in spite of elevated GSH contents. There was no clear relationship between intracellular GSH concentrations and the anti-inflammatory effects of curcumin.