GLUCOCORTICOIDS INCREASE THE ACCUMULATION OF REACTIVE OXYGEN SPECIES AND ENHANCE ADRIAMYCIN-INDUCED TOXICITY IN NEURONAL CULTURE

Glucocorticoids (GCs), the adrenal steroids secreted during stress, ar e known to affect diverse processes involving reactive oxygen species, from exacerbation of ischemic damage to alteration of antioxidant enz yme activities. To determine whether GCs have a direct effect on oxida tive processes, we constructed a dose-response curve using adriamycin, an oxygen radical generator, in primary neuronal cultures. In culture s derived from the hippocampus, which has the greatest concentration o f corticosteroid receptors in the brain, higher levels of GCs signific antly increased adriamycin toxicity, while not being toxic themselves. In cortical cultures, which contain lesser amounts of corticosteroid receptors, GCs had no effect on the adriamycin dose-response. Surprisi ngly, when tested with dichlorofluorescein for levels of reactive oxyg en species (ROS), GCs increased ROS by approximately 10% basally and a t all adriamycin doses in both hippocampal and cortical cultures. Thus , greater generation of ROS does not account for the increased suscept ibility of the hippocampus to oxidative damage. (C) 1996 Academic Pres s, Inc.