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Abstract human bodies contain an affluent adrenal
steroid, dehydroepiandrosterone (DHEA) which is the precursor
of both male and female sex hormones. DHEA reaches the highest
level at approximately 25 years of age and declines dramatically
afterwards, with only approximately 10 % DHEA remaining at the
age of 70 or 80. In addition, the hormone may postpone and even
reverse aging process. Whether this phenomenon is affected by
oxidative stress and antioxidative ability was an important
point of investigation of this thesis. DHEA has also been shown
to have a variety of physiological functions against obesity,
cancer and atherosclerosis. However DHEA has also been shown to
be involved in carcinogenesis or to alter G6PD activities and
enhance lipid peroxidation. To determine the effect of dietary
antioxidants on the tissue contents and the toxicity and
antioxidative activity of DHEA, three studies were conducted in
: ( I ) effect of dietary selenium and vitamin E on tissue and
serum levels of dehydroepiandrosterone in rats; ( II ) dietary
vitamin E modifies in vivo toxicity of dehydroepiandrosterone in
rats; ( III ) hemolytic effects of dehydroepiandrosterone in
vitro. The three studies are : ( I ) Effect of dietary
selenium and vitamin E on tissue and serum levels of
dehydroepiandrosterone in rats: Male Sprague-Dawley rats (4-wk
old) were fed diets deficient in or supplemented with 0.2 ppm Se
with or without adequate (30 IU/kg diet) and high (200 IU/kg
diet) levels of vitamin E for six weeks. The results showed that
both Se and vitamin E supplementation significantly increased
the relative testis weight. As expected, serum glutathione
peroxidase activity was high in Se-supplemented rats and very
low in Se-deficient rats. In the adrenal, the concentration of
DHEA was significantly increased by supplementation of either
dietary Se or vitamin E. However, high vitamin E did not further
increase the adrenal DHEA level, and there was no interaction
between the two dietary factors. Dietary vitamin E at 30 IU/kg
significantly increased brain DHEA levels in rats fed Se-
deficient but not Se-adequate diets while high vitamin E did not
further increase the DHEA levels. Similarly, the serum DHEA
level was only affected by dietary vitamin E, whose effect was
not dependent on Se. The results demonstrate that tissue and
serum levels of DHEA are mainly affected by dietary vitamin E
which at levels beyond 30 IU/kg afforded no additional
steroidogenic effect in young rats. ( II ) Dietary vitamin
E modifies in vivo toxicity of dehydroepiandrosterone in rats:
Male Sprague-Dawley rats (4-wk old) were fed vitamin E-deficient
or vitamin E-adequate (30 IU/kg) diet for four weeks before
being injected i.p. with DHEA for one week. The results showed
that DHEA injected at 100 mg/kg for 7 days significantly
decreased body weights of vitamin E-deficient rats. DHEA dose-
dependently increased the relative liver and kidney weights
(g/100 g body weight) regardless of dietary vitamin E status
while the relative adrenal weight was increased by the steroid
only in vitamin E-deficient rats. DHEA significantly increased
hepatic NPSH and TSH contents but the effect was not dose-
dependent or was affected by vitamin E. DHEA injected at 100 mg/
Kg significantly increased plasma ALT activity in vitamin E-
deficient rats only. DHEA decreased (P < 0.05) hepatic GST
activity in vitamin E-deficient rats to a greater extent than in
vitamin E-sufficient rats. By contrast, DHEA increased (P <
0.05) hepatic G6PD activity in vitamin E-deficient rats to a
greater extent than in vitamin E-sufficient rats. Both the in
vivo and in vitro lipid peroxidation of liver (induced by
incubation with 100 mM FeCl3) were significantly decreased by
DHEA injection and by dietary vitamin E, but the effect of DHEA
was only significant in the vitamin E-deficient rats. The
present study demonstrates that injection with DHEA for 7 days
results in overt toxicity including increased weights of liver,
kidney and adrenal and altered hepatic enzyme activities.
Dietary vitamin E deficiency led to elevated plasma ALT activity
induced by DHEA and to greater changes in hepatic enzymes
assayed. That DHEA inhibited hepatic lipid peroxidation only in
vitamin E-deficient rats suggests that the steroid may have some
antioxidant activity which is masked by vitamin E when the
latter is sufficient. ( III ) Hemolytic effects of
dehydroepiandrosterone in vitro: DHEA induced lysis of human red
blood cells (RBCs) in a concentration-dependent manner, with ca.
70 % hemolysis at 2 mM DHEA at 37℃ for 1 hr. Hemolysis induced
by 2 mM DHEA was rapid and involved neither hemoglobin oxidation
nor lipid peroxidation. The hemolysis was also not inhibited by
addition of EDTA, catalase, superoxide dismutase, glucose, or a
radical scavenger including mannitol, dimethylsulfoxide and a-
tocopherol, indicating a non-oxidative mechanism. RBCs stored
overnight before incubation with DHEA were hemolyzed to a lesser
extent than the freshly prepared RBCs. Light microscopy of the
fresh RBCs following 1-h incubation with 2 mM DHEA revealed
thickened and cup-shaped deformity of the membranes, suggesting
a change in the membrane structure possibly due to the
intercalation of the steroid into the membranes. The
results of above studies demonstrated that the DHEA contents of
tissues were affected by vitamin E and selenium in young rats,
it may be the activities of antioxidants protected tissues
against the stress of free radicals. In contrast, tissues were
attacted by free radicals when the tissues were deficient
antioxidants, and it was diminished the production or contents
of DHEA .Therefore, supplementation of antioxidants may be
avoided the contents of DHEA diminished by oxidative stress. In
the other hand, when supplementation of DHEA must be pay
attention to negative effect on high doses of DHEA. And it must
be careful the type of supplemetation of DHEA especially the i.v
injection, because it may be cause the hemolysis. In this study,
the results demonstated that DHEA is a weak antioxidants, it
altered the activities of antioxidative enzyme in vivo, but the
mechanism is not clear.
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