Influence of cell culture conditions on the protective effect of antioxidants against beta-amyloid toxicity: studies with lazaroids.

The mechanisms of cell death of rat cortical neurons chronically exposed to the beta-amyloid (betaA) biologically active fragment beta-(25-35) involve oxidative stress. We examined the influence of culture conditions on the neuroprotective activity of antioxidants against beta-(25-35) toxicity. Common radical scavengers such as N-acetylcysteine (250 microM) and N-t-butyl-phenylnitrone (500 microM) only protected cortical cells cultured in the presence of fetal calf serum (FCS) from betaA insult. The neuroprotective effect of lazaroids (U74389G and U83836E), 21-aminosteroids with antioxidant activity, was tested in cells grown with or without FCS. U74389G did not interfere with beta-(25-35) toxicity in either condition, while U83836E at a very low concentration (15 nM) protected cortical cells exposed to the beta peptide only when the neurons were cultured in the presence of FCS. These data show that a lazaroid can prevent beta-(25-35) toxicity and that the antioxidants exerted their protective effect in certain conditions.