SCAVESTROGENS PROTECT IMR-32 CELLS FROM OXIDATIVE STRESS-INDUCED CELL-DEATH

Oxidative stress is considered an important pathophysiological mechani sm contributing to promote cell death in a broad variety of diseases i ncluding cardiovascular and neurodegenerative disorders. The so-called scavestrogens J811 and J861, structurally derived from 17 alpha-estra diol, are potent radical scavengers and inhibitors of iron-induced cel l damage in vitro. In this study the potential cytoprotective effects of the scavestrogens J811 and J861 against Fenton reagent-induced cell damage (50 mu M FeSO4 plus 200 mu M H2O2) were compared with those of 17 alpha- and 17 beta-estradiol. Cell viability studies using Trypan blue staining showed that estradiols and scavestrogens at concentratio ns ranging from 0.1 to 10 mu M are able to protect IMR 32 neuroblastom a cells from Fenton-mediated death. In addition, these compounds decre ased lipid peroxidation measured as thiobarbituric acid reactive subst ances and renormalize oxidative stress-increased intracellular glutath ione levels. When given 6 h after the toxic stimulus, J811 and J861 re scued 60% of cells, whereas 17 alpha- and 17 beta-estradiol were ineff ective. These results suggest that the scavestrogens J811 and J861 are powerful antioxidants capable of interfering with radical-mediated ce ll 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. (C) 1998 Academic Press.