Am. Leal et al., CYTOPROTECTIVE ACTIONS OF ESTROGENS AGAINST TERT-BUTYL HYDROPEROXIDE-INDUCED TOXICITY IN HEPATOCYTES, Biochemical pharmacology, 56(11), 1998, pp. 1463-1469
Estrogens are effective antioxidants in diverse biological systems. De
spite their antioxidant activities, it is not known yet whether estrog
ens prevent or alleviate liver toxicity induced by oxidative stress. I
n the present work, we studied this possibility by examining in vitro
the protective potential of different estrogen compounds (17 beta-estr
adiol, 2-hydroxyestradiol, and -diethylstilbestrol) against tert-butyl
hydroperoxide-induced hepatocyte damage. Various parameters such as c
ell viability, lipid peroxidation, adenine nucleotide content, and thi
ol status were measured as an index of cytotoxicity. The protective ef
fects of estrogens were compared to those of the iron chelator deferox
amine. The molecules tested prevented oxidant-induced cell death diffe
rently, showing variable degrees of protection. Deferoxamine was the m
ost potent agent, followed by diethylstilbestrol and 2-hydroxyestradio
l, 17 beta-estradiol being the least efficient. The inhibitory effects
on lipid and thiol oxidations paralleled the effects on cell viabilit
y. The molecules also reduced the oxidant-induced ATP depletion, excep
t for 17 beta-estradiol which had no effect an the decreased ATP level
s. Our results suggest that the mechanisms of the preventive actions o
f estrogens may be related not only to their antioxidant activity agai
nst free radicals, but also and to a lesser extent to the maintenance
of the normal redox status of the cell, which partially recovers the i
ntracellular GSH levels. BIOCHEM PHARMACOL 56;11:1463-1469, 1998. (C)
1998 Elsevier Science Inc.