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 microM FeSO(4), 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 EC(50s) of each substance were 4 and 4.6 microM. The maximal effect was obtained at a 25-microM 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 microM+TX 12.5 microM) 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.
Boland
A
A
Laboratory of Pharmacology, Institute of Pathology B23, University of Liege, B-4000, Liege, Belgium.
Delapierre
D
D
Mossay
D
D
Hans
P
P
Dresse
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005296:Ferrous Compounds; D016166:Free Radical Scavengers / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D002839:Chromans; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D010545:Peroxides; D020011:Protective Agents; D007501:Iron; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D015742:Propofol