Propofol protects cultured brain cells from iron ion-induced death: comparison with trolox

The anesthetic propofol (PPF) has been shown to be an antioxidant in acellu lar experiments. This study was designed to assess the ability of PPF to pr otect primary-cultured brain cells against iron-mediated toxicity. A compar ison with trolox (TX), a hydrosoluble vitamin E analogue, was performed. Ra t cortical cells were exposed to 10 mu M FeSO4. PPF and/or TX. After a 4-h incubation, PPF and TX improved cell survival (lactate dehydrogenase measur ements) in a concentration-dependent manner. The respective EC50s of each s ubstance were 4 and 4.6 mu M. The maximal effect was obtained at a 25-mu M concentration which is similar to concentrations of PPF used clinically. Th e combination of both drugs at certain concentrations showed a complete pro tection of the cells, a significant decrease in intracellular peroxide prod uction (dichloro-fluorescein diacetate (DCF-DA) fluorescence, 4-h incubatio n), in lipoperoxidation (thiobarbituric acid reactive substances fluorescen ce, PPF 6.25 mu M + TX 12.5 mu M) and an additive protective effect. This w as true after 4- and 16-h incubation. These data suggest that PPF is neurop rotective. Moreover, the combination with a vitamin E analogue confers long duration protection against oxidative stress. (C) 2000 Elsevier Science B. V. All rights reserved.