Protective effect of estradiol on hepatocytic oxidative damage.
OBJECTIVE
To examine the protective effect of estradiol on the cultured hepatocytes under oxidative stress.


METHODS
Hepatocytes of rat were isolated by using perfusion method, and oxidative stress was induced by a serum-free medium and FeNTA. MDA level was determined with TBA method. Cell damage was assessed by LDH assay. Apoptosis of hepatocytes was assessed with cytoflowmetric analysis. Expression of Bcl-xl in cultured hepatocytes was detected by Western blot. The radical-scavenging activity of estradiol was valued by its ability to scavenge the stable free radical of DDPH.


RESULTS
Oxidative stress increased LDH from 168 +/- 25 x 10(-6)IU.cell(-1) to 780 +/- 62 x 10(-6)IU.cell(-1) and MDA(from 0.28 +/- 0.07 x 10(-6)nmol.cell(-1) to 1.35 +/- 0.12 x 10(-6)nmol.cell(-1)) levels in cultured hepatocyte, and estradiol inhibited both LDH and MDA production in a dose dependent manner. In the presence of estradiol 10(-6)mol.L(-1), 10( -7 )mol.L(-1) and 10(-8)mol.L(-1),the LDH levels are 410 +/- 53 x 10(-6)IU.cell(-1) (P<0.01 vs oxidative group), 530 +/- 37 X 10(-6)IU.cell(-1 ) (P<0.01 vs oxidative group), 687+/-42 x 10(-6)IU.cell(-1) (P<0.05 vs oxidative group) respectively, and the MDA level are 0.71+/-0.12 x 10(-6)nmol.cell(-1) (P<0.01 vs oxidative group),0.97+/-0.11 x 10(-6)nmol.cell(-1 )(P<0.01 vs oxidative group) and 1.27+/-0.19 x 10(-6)nmol.cell(-1) respectively. Estradiol suppressed apoptosis of hepatocytes induced by oxidative stress, administration of estradiol(10(-6)mol/L)decreased the apoptotic rate of hepatocytes under oxidative stress from 18.6 +/- 1.2% to 6.5 +/-2.5%, P<0.01. Bcl-xl expression was related to the degree of liver cell damage due to oxidative stress, and estradiol showed a protective action.


CONCLUSIONS
Estradiol protects hepatocytes from oxidative damage by means of its antioxidant activity.
Liu
Yan
Y
Department of Biology, Medical School of Fudan University, 130 Dongan Road, Shanghai 210032, China. liya9899@yahoo.com
Shimizu
Ichiro
I
Omoya
Toshihiro
T
Ito
Susumu
S
Gu
Xiao-Song
XS
Zuo
Ji
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D017392:Thiobarbituric Acid Reactive Substances; D051020:bcl-X Protein; D004958:Estradiol; D007770:L-Lactate Dehydrogenase