Scavestrogens protect IMR 32 cells from oxidative stress-induced cell death.
Oxidative stress is considered an important pathophysiological mechanism contributing to promote cell death in a broad variety of diseases including cardiovascular and neurodegenerative disorders. The so-called scavestrogens J811 and J861, structurally derived from 17alpha-estradiol, are potent radical scavengers and inhibitors of iron-induced cell damage in vitro. In this study the potential cytoprotective effects of the scavestrogens J811 and J861 against Fenton reagent-induced cell damage (50 microM FeSO4 plus 200 microM H2O2) were compared with those of 17alpha- and 17beta-estradiol. Cell viability studies using Trypan blue staining showed that estradiols and scavestrogens at concentrations ranging from 0.1 to 10 microM are able to protect IMR 32 neuroblastoma cells from Fenton-mediated death. In addition, these compounds decreased lipid peroxidation measured as thiobarbituric acid reactive substances and renormalize oxidative stress-increased intracellular glutathione levels. When given 6 h after the toxic stimulus, J811 and J861 rescued 60% of cells, whereas 17alpha- and 17beta-estradiol were ineffective. These results suggest that the scavestrogens J811 and J861 are powerful antioxidants capable of interfering with radical-mediated cell death in diseases known to be aggravated by reactive oxygen species. Such compounds may be useful in the development of novel treatments for stroke or neurodegenerative disorders.
Department of Psychiatry, University of Würzburg, Würzburg, Germany.
D
D
Blum-Degen
M
M
Haas
S
S
Pohli
R
R
Harth
W
W
Römer
M
M
Oettel
P
P
Riederer
M E
ME
Götz
D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000975:Antioxidants; C045076:Fenton's reagent; D016166:Free Radical Scavengers; C115406:J811 scavestrogen; C115405:J861 scavestrogen; D017392:Thiobarbituric Acid Reactive Substances; D004958:Estradiol; D006861:Hydrogen Peroxide; D007501:Iron; D005978:Glutathione