Protective effect of 17-beta-estradiol in human neurocellular models of lead exposure.
The developing nervous system has long been recognized as a primary target site for lead (Pb)-induced toxicity. Pb-exposure causes cognitive dysfunction, growth retardation, hyperactivity and neurochemical deficits in animals and humans. In the present study the effects of 17-beta-estradiol on human SH-SY5Y neuroblastoma cells in culture exposed to low-levels of Pb were assessed. The cells were exposed to Pb (0.01-10 microM) for 48 h and cell proliferation was determined by the MTT reduction assay. Pb significantly inhibited the proliferation and growth of neuroblastoma cells in a concentration-dependent manner. A 50% inhibition (IC50) in the proliferation of cells was observed with 5 microM Pb. Exposure of cells to Pb (5 microM) for 48 h resulted in a significant increase (+732% of control) in caspase-3 activity, an indicator of apoptosis and total cellular prostaglandin E2 level (+1180% of control), marker of programmed cell death/neuronal cell loss. Pretreatment with 17-beta-estradiol (10 nM) effectively blocked the effects of Pb on caspase-3 activity but not prostaglandin E2 level. Further, Pb but not 17-beta-estradiol in a concentration (0.1-10 microM)-dependent manner effectively decreased (38-84%) the cellular concentration of glutathione (GSH), an important intracellular antioxidant. However, the effect of Pb on GSH level was effectively blocked when pretreated with 17-beta-estradiol. The data indicate that even low concentrations of Pb can be detrimental and potentially toxic to the developing brain. In conclusion, these results suggest that at least some of the neurotoxic effects of Pb may be mediated by apoptosis, which by pretreatment with 17-beta-estradiol can be prevented. This study further confirms previous reports of 17-beta-estradiol acting as a neuroprotective and antiapoptotic agent during induced toxic stress conditions.
Chetty
Chellu S
CS
Savannah State University, Savannah, GA 31404, USA. chettyc@savstate.edu
Vemuri
Mohan C
MC
Reddy
Gottipolu R
GR
Suresh
Challa
C