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 acellular experiments. This study was designed to assess the ability of PPF to protect primary-cultured brain cells against iron-mediated toxicity. A comparison with trolox (TX), a hydrosoluble vitamin E analogue, was performed. Rat 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 measurements) in a concentration-dependent manner. The respective EC50s of each substance 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. The combination of both drugs at certain concentrations showed a complete protection of the cells, a significant decrease in intracellular peroxide production (dichloro-fluorescein diacetate (DCF-DA) fluorescence, 4-h incubation), in lipoperoxidation (thiobarbituric acid reactive substances fluorescence, PPF 6.25 mu M + TX 12.5 mu M) and an additive protective effect. This was true after 4- and 16-h incubation. These data suggest that PPF is neuroprotective. Moreover, the combination with a vitamin E analogue confers long duration protection against oxidative stress. (C) 2000 Elsevier Science B.V. All rights reserved.