Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
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ISSN 2072-3875
ANOBOLIC ANDROGENIC STREROIDS IN MALE ADULTS
MICE INDUCED : HYPOTHYRODISIM , OXIDATIVE
STRESS
Shaima Obead Abde-Allh Shaima Ahmed Rahim
collage of science for woman / Babylon university
Abstract :
Thyroid function is affected by AAS used in humans, although the mechanisms of
the effects of androgenic anabolic steroid (AAS) are unclear. The present study is
designed to know the effect of AAS in thyroid function and oxidative stress.
Experimental animals used in the study(30 Swiss mice) were allocated to three
groups as general control group, and test groups(N=10). The test groups received
(5,10) mg/kg of body weight nandrolone Decanoate by subcutaneous injection each 48
hours , but control groups received the same volume of normal saline . The duration
of the experiment was 4-weeks. Blood samples were collected after two days at the
end of experimental period from the control and treated groups. The serum samples
were assayed for (TSH,T3,T4, total cholesterol , MDH,GSH,) Results revealed that all
ND-treated animals exhibited a significant increase of body weight (B.W) and serum
TSH hormone, total cholesterol, MDA, a significant decrease was found in GSH
level,T3 and T4 hormone, Our data of this study indicate that anabolic steroids at
supraphysiological doses exerts direct actions on the thyroid gland and might lead to
thyroid dysfunction and increase of oxidative stress of males .Testosterone or its
derivatives such as Nandrolone Decanoate are being problem commonly. Athletes,
coaches, and physicians should be aware of their harmful side effects.
السترويذاث الابتنبئيت الانذروجينيت سببج انخفبض الذرقيت وزيبدة الجهذ التأكسذي في ركىر الفئراى
البيض
شيوبء عبيذ عبذالله شيوبء احوذ رحين
كليت العلىم للبنبث / جبهعت بببل
الخلاصت :
حعذ انغذة انذرق تُ ي اكبز انغذد ف انجسى وانخ حخأثز وظائفها بشكم كب زُ بانسخ زُو ذَاث الا ذَروج تُُُ
ان سًخع هًت ي قبم الا سَا ،ٌ بانزغى ي ا ي كُا كَُ تُ حأث زُ هذ ان زًكباث ف وظ فُت انغذة انذرق تُ نى حخىضح بشكم
هَائ .نذا ص جًً هذ اانذراست ن عًزفت حأث زُ انسخ زُو ذَاث الابخ اُئ تُ الا ذَروج تُُُ ف وظ فُت انغذة انذرق تُ وانجهذ
انخأكسذ .
اسخخذو ف انذراست 30 فأراَ اب ضُاَ سى سَز اََ وانخ وضعج ف ثلاد يج ىًعاث ،ان جً ىًعت الاون عذث
ك جً ىًعت س طُزة وانخ عىيهج بان حًهىل ان هًح انفس ىُنىج ، ف اًُ عىيهج ان جً ىًعت انثا تَُ وانثانثت بانعقار
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
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ISSN 2072-3875
10 ( يهغى / كغى ي وس انجسى ححج انجهذ يذة انخجزبت اسخ زًث اربعت اساب عُ وكا انعقار ، ع ذُ انخزك شُ) 5
عَط نهح ىُا اَث كم 48 ساعت . بعذ هَا تَ انخجزبت ب ىُي وس جَ انح ىُا اَث ثى شزحج وج عًج ع اُُث انذو
نحساب انهزيى ان حًفش نهذرق تُ وهزيى اَث انذرق تُ فضلاَ ع يسخىي انكىن سُخزول انكه وانجهذ انخأكسذ ان خً ثًم بق اُص يسخىي انكهىحاث ىُ وان اًنى ذَ هَا ذَ .
ب جُُ خَائج انذراست حصىل حغ زُاث يع ىُ تَ ف يعا زَُ انذراست ج عًُا ف ج عًُ انح ىُا اَث ان سًخه تً نهعقار
وهذا ح ثًم بش اَدة يع ىُ تَ ف وس انجسى انعاو و يسخىي انهزيى ان حًفش نهذرق تُ ويسخىي انكىن سُخزول انكه وان اًنى ذَ هَا ذَ . ف اًُ سجهج ان خُائج حصىل قَصا يع ىُ ف هزيى اَث انذرق تُ ويسخىي انكهىحاث ىُ .
اوضحج خَائج انذراست با انهزيى اَث الابخ اُئ تُ فىق انجزعت انفس ىُنىج تُ ح خًهك حأث زُ س ءٍ عه انغذة انذرق تُ
رب اً ؤَد ان حذود خهم ف ع هًها فضلاَ ع س اَدة انجهذ انخأكسذ ف انذكىر.ا اساءة اسخع اًل يثم هذة
انعقاق زُ اصبحج يشكهت صح تُ كب زُة ي اً عَ ح فُ ذُ انخطىاث وانبزايج انضزور تَ لارشاد ان زًاهق وانشباب
ي الاثار انسهب تُ ن ثًم هذة ان زًكباث نهحذ ي ا خَشارها.
Introduction :
Endocrine system is the second key
regulator of various body system
functions after nervous system(2013,
AbdAlla). One of the largest endocrine
glands in the body is The Thyroid gland
It is positioned on the neck
(2014,Peepre et al) just below the
Larynx and has two lobes with one on
either side of the trachea. The thyroid
gland is genetically programmed to be
the metabolic regulator in all
vertebrates because It is involved in the
production of two amino acid-iodine
bound hormones known as 3-5-3’
triiodothyronine (T3) and 3-5-3’-5’
tetraiodothyronine (T4, thyroxine) The
thyroid gland secretes the hormone
thyroxine (T4) along with small
amounts of triiodothyronine (T3). The
most of the T3 in the circulation (about
80%) is formed from the conversion of
T4 to T3 by the deiodinase enzyme.
Most of this transformation takes place
in the kidney and liver. T3 is
considered the physiologically active
hormone; in this sense T4 can be
thought as a prohormone(2011,Russell
and Joffe) .
The thyroid also produces and
releases the hormone calcitonin
(thyrocalcitonin) which contributes to
the regulation of blood calcium levels.
calcitonin reduced the concentration of
calcium in the blood. Majority of the
calcium removed from the blood is
stored in the bones.
The Production of T3 and T4 are
regulated by thyroid stimulating
hormone (TSH), which produced by the
pituitary gland. Higher levels of TSH
lead to higher rates of hormone
production and secretion from the
thyroid. TSH in turn is regulated by
another hormone secreted from the
hypothalamus, thyrotropin-releasing
hormone (TRH). TSH levels are also
regulated in a negative feedback
manner by the levels of circulating
thyroid hormone, when T3 and T4
levels are too low TSH Production is
increased (2000,Hulbert) . These
hormones increase the metabolic
activity of the body cells and released
throughout the body to direct the body
metabolism. They stimulate all body
cells to work at a better metabolic rate.
Without these hormones the body s
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
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ISSN 2072-3875
cells would not be able to regulate the
speed at which they performed
chemical actions. Their release will be
increased under certain situations such
as cold temperatures when a higher
metabolism is needed to generate
heat(1975,Balsam and Sexton).
Anabolic–androgenic steroids (AAS)
are a class of compounds that include
any drug or hormonal substance,
pharmacologically and chemically
related to testosterone that stimulates
the growth or manufacturing of bone
and muscle(anabolic effect)
(2008,Salas-Ramirez et al) These
substances are frequently misused by
athletes, bodybuilders and youths in
order to increase muscle mass or
enhance physical endurance
(2004,Bahrke and Yesalis; 2005,Thiblin
and Petersson) Of AAS, nandrolone,
19-nortestosterone (C18H26O2), has a
stronger anabolic capacity (about 5
times higher) than testosterone
(2006,Chrousos). Nandrolone is either
chemically synthesized or naturally
found in some mammals, including
human and farm animals.
Thyroid gland is one of the nonclassical
target organs for sex steroids
(2006,Bermudez et al) . Thus
Administration of sex hormones can
interfere substantially with the
hypothalamic–pituitary–thyroid (HPT)
axis (2006,Bisschop et al,). Androgen
administration in women decreases T4
substitution in patients with primary
hypothyroidism (1994,Arafah).
Thyroid hormones regulate oxidative
metabolism and thus play an important
role in free radical production. Hence
variations of thyroid hormone levels
can be one of the main physiological
modulators of in vivo cellular oxidative
stress due to their known effects on
mitochondrial respiration
(1999,Guerrero et al.). These conditions
determine a higher consumption of
cellular antioxidants (1986,Sies; 1988
Fernandez et al.; 1998, Huh et al.) and
inactivation of antioxidant enzymes
(1988,Fernandez et al.), thus inducing
oxidative stress (1986,Sies) with the
concomitant increase in lipid
peroxidation and protein oxidation
(2011,Pasupathi and Latha)., One of the
major effects of thyroid hormones is to
increase mitochondrial respiration
which results in increased generation of
reactive oxygen species (ROS)
(1978,Nishiki et al,).
Material and Methods :
Laboratory animals :
The research was conducted on 30 of
Swiss mice 12 weeks old, weight (25-
28) g. were brought from the animal
house of science collage/Babylon
university , Animals had free access to
tap water and standard food pellet. and
they were housed in metal cages under
normal laboratory conditions in a room
with an ambient temperature of 21±1°C
and 12/12 light/dark photoperiod. The
animals acclimatized for 2 weeks
before the onset of experiment.
Experimental protocol :
The animals were weighed and
divided into three groups of 10 animals
each:
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
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Group I: Control group which injected
with normal saline for 4 weeks .
Group II: test group which injected
subcutaneous at 5 mg/kg/b.wt.by
nandrolone Decanoate for 4 weeks .
Group II: test group which injected
subcutaneous at 10 mg/kg/b.wt.
nandrolone Decanoate for 4 weeks.
Tested Materials:
Anabolic androgenic steroid
(Nandrolone Decanoate)) (produced by
Nile Co., Egypt, under license from
N.V. Organon, Oss, Holland) was
purchased from a local pharmacy in a
form of injection. It is an AAS with a
chemical formula . (C28 H44 O3 ). The
drug was diluted to the selected dose in
a normal salin .
Collecting of blood sample :
Two days after the final drug
administration, body weight was
measured and the mice were killed
rapidly under ether anesthesia followed
by cervical dislocation. The following
samples Blood was collected via heart
puncture, centrifuged at 2,000 rpm for
10 min and the supernatant (serum) was
stored at -20?C. The serum was used to
measure level T3,T4,TSH, total
cholesterol, malondialdehyde (MDA)
and glutathione (GSH) level.
Measurements :
Serum thyroid stimulating hormone
(TSH), triiodothyronine (T3) and
thyroxine (T4) were measured by kits
method using enzyme – linked
immunosorbent assay (ELISA) .the
kits is available from Germany Biochek
–Inc. Company.
Total cholesterol were determined in
serum using commercial kits from Bio
Merieux, France.
Fatty acids oxidation was determined
by measurement of Malondialdehyde,
as a product of polyunsaturated using
thiobarbituric acid reactive substances
(TBARS) was measured
spectrophotometrically, after the
reaction with thiobarbituric acid in
acidic medium for 30 min with heating.
To form chromogen complex reactive
product, the absorbance of the resultant
pink product can be measured at 532
nm (1979,Moron et al) and its
concentration was calculated using the
extinction coefficient value1.56 ×
105M-1 cm-1 and resus are expressed
as mmol MDA/L .
Glutathione was assayed using
dithiobis-2-nitrobenzoic acid (DTNB)
in alkaline medium(pH=8) . The
reaction color was read at 412 nm.
(1979,Moron et al) ( GSH levels were
calculated using an extinction
coefficient of 13600M?1 cm?1. Results
are expressed in _?mol GSH/L.(
1979,Moron et al).
Statistical Analysis :
The statistical analysis was
performed using SPSS statistical
program version 17 . All data were
expressed as mean ± SD of number of
experiments. The statistical significance
was evaluated by t-test. Value of P <
0.05 was considered statistically
significant.
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
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ISSN 2072-3875
Result and Dissection :
The data in figure (1) showed a
prominent significant increase in B .W.
after anabolic steroid intake compared
to control animals (at p? 0.05).
Androgenic Anabolic steroids seem to
be effective in two ways:
Figure(1)Changes in different of body weight(gm) in treatment groups .values are
M± S.E.,* P?0.05 compared to control group.
the first way was by convert a negative
nitrogen balance to positive
one through improving the use of
ingested protein and increase protein
synthesis in skeletal muscle. Anabolic
steroids are believed to exert their
effects by binding to androgen
receptors, that are present in the
reproductive tissue as well as in many
non-reproductive tissues, including,
skeletal muscle bone, brain, liver,
kidney, prostate and adipocytes
(2001,Shahidi ; 2010, Attardi et al)
which then translocate binding sites on
chromatin, promoting gene
transcription, stimulating production of
mRNA and protein synthesis (2009,Li,
and Al-Azzawi). The second way was
by anabolic Steroids compete
glucocorticosteroid receptors, leading
to reduce protein catabolism. Thus, the
anabolic action of androgens is
mediated directly through androgenreceptor
binding and also indirectly by
antiglucocorticoid action (1990
,Hickson et al).
In our study the anabolic steroid
treated animal exerted significant
increase of body weight compared to
control animal (figure 1) could be a
consequence of the increased anabolism
and utilization of nitrogen of ingested
protein, in tissue building.
Thyroid gland have androgen
receptors and the sex steroids might
directly influence on thyroid function.
(2002,Banu et al). showed that
testosterone stimulates thyrocyte
proliferation in culture, an effect
independent of TSH. In rats,
testosterone might increase TSH
synthesis and secretion.( 1998, Borges
et al).
Nandrolone administration bring
significant changes in the TSH ,T3 , T4
levels at the doses used. Figure ( 2)
illustrates the levels of serum thyroid
stimulating hormone (TSH) as
0
1
2
3
4
5
6
7
control 5mg/kg 10mg/kg
different body weight(gm
concentration ofAAS(mg/kg)
*
*
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
21
ISSN 2072-3875
compared to control group was
significantly increased . Also figure 3
and 4 is showing The levels of T3, and
T4 was significantly decreased as
compared to control(at p? 0.05).
One of the most prominent effects of
anabolic steroid is the interfere
substantially with the hypothalamic–
pituitary–thyroid (HPT)
axis(2006,Rodrigo,et al,). In a clinical
study, Deyssig and Weissel (1993)
showed that total T4, total T3, and
thyroid hormone-binding globulin
(TBG), were significantly decreased,
also TRH stimulation was increased in
five bodybuilders who used high
concentrations of AAS compared with
eight control subjects. Thus, the abuse
of androgenic anabolic steroid may
cause impairment of thyroid
function . In the present study, the
anabolic steroid-treated animals had a
significant reduction in serum total T3,
T4, and significant increase TSH level
(figure 2 , 3 and 4) , the reduction in
total T3 andT4 level could be explained
by reduction a thyroid binding globulin
(TBG). The levels of TBG influence the
levels of total thyroid hormone in
circulation. If TBG level is depressed,
total T4 and T3 levels will go down. An
increase in TBG due to higher levels of
total thyroid hormone. However note
that the small ratio of T3 and T4 remain
unbound to TBG (0.05% of T4 and
0.5% of T3), the so-called free fraction
(1987,Alen et al), Thyroid Stimulating
Hormone (TSH) levels. Typically
increase in hypothyroidism, the thyroid
is not secreting adequate concentration
of T4, and in an attempt to stimulate the
thyroid, the pituitary gland secretes
excess TSH. So TSH is HIGH in
hypothyroidism. The opposite is
observed in hyperthyroidism: the
excess thyroid hormone in circulation
acts back on the pituitary to suppress
TSH production. in hyperthyroidism
TSH is LOW.
Figure (5) showed that, nandrolone
treatment induced a significant
elevation in serum cholesterol levels all
over the experimental groups.
When the thyroid hormones level slows
down (hypothyroidism), it also slows
down the body ability to process
cholesterol. This processing lag is
largely explained by a decreasing in the
activity and number of what are known
as(low-density
lipoproteins) LDL receptors and
apolipoprotein B (apo A) in liver LDL
receptors help remove bad cholesterol
from the body; when the number of
receptors decreases, LDL accumulates
in the bloodstream, acting to increase
both LDL and total cholesterol
levels.The high-density lipoprotein
(HDL) levels are normal or even
elevated in severe hypothyroidism
because of decreased activity of
cholesteryl-ester transfer protein
(CETP) and hepatic lipase (HL), which
are enzymes regulated by thyroid
hormones. The low activity of CETP
and more specifically of hepatic lipase,
results in decrease transport of
cholesteryl esters from HDL(2)to very
low-density lipoproteins (VLDL) and
intermediate low-density lipoprotein
(IDL), and reduce transport of HDL(2)
to HDL(3). Moreover, hypothyroidism
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
22
ISSN 2072-3875
increases the oxidation of plasma
cholesterol mainly because of an altered
pattern of binding and to the increased
levels of total cholesterol, which
presents a substrate for the oxidative
stress. Overt hypothyroidism is
characterized by hypercholesterolemia
and a marked increase in low-density
lipoproteins (LDL)) because of a
reduced fractional clearance of LDL by
a decrease number of LDL receptors in
the liver (2002,Duntase) On the other
hand , nandrolone has higher ability to
induce hepatic triglyceride lipase(
HTGL) which may explain our results
in which nandrolone has an increasing,
effect on LDL and reduced effect on
HDL levels. It is worth mentioned that,
the marked increased levels of total
cholesterol (2003,Maron) which
presents a substrate for the oxidative
stress.
Concerning the effect of nandrolone
on serum oxidants/ antioxidants status
(figure 6 and 7), statistical analysis
revealed a significant increase of MDA
and a significant decrease of GSH
contents (p ? 0.05) compared to control
.
Figure(2)Changes in TSH concentration (ng/L) in treatment groups .values are
M± S.E.,* P?0.05 compared to control group.
Figure(3)ChangesinT3(ng/dl)concentration in treatment groups .values are
M±S.E., * P?0.05 compared to control group
0
0.5
1
1.5
2
control 5mg/kg 10mg/kg
TSH concentration(
concentration of AAS(mg/kg)
0
0.2
0.4
0.6
0.8
control 5mg/kg 10mg/kg
concentration of T3
concentration of AAS(mg/kg)
*
*
* *
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
23
ISSN 2072-3875
Figure(4)Changes in T4 concentration (?g/dl) in treatment groups .values are M±
S.E.,* P?0.05 compared to control group.
One of the most prominent effects of
anabolic steroid is the interfere
substantially with the hypothalamic–
pituitary–thyroid (HPT)
axis(2006,Rodrigo,et al,). In a clinical
study, Deyssig and Weissel (1993)
showed that total T4, total T3, and
thyroid hormone-binding globulin
(TBG), were significantly decreased,
also TRH stimulation was increased in
five bodybuilders who used high
concentrations of AAS compared with
eight control subjects. Thus, the abuse
of androgenic anabolic steroid may
cause impairment of thyroid
function . In the present study, the
anabolic steroid-treated animals had a
significant reduction in serum total T3,
T4, and significant increase TSH level
(figure 2 , 3 and 4) , the reduction in
total T3 andT4 level could be explained
by reduction a thyroid binding globulin
(TBG). The levels of TBG influence the
levels of total thyroid hormone in
circulation. If TBG level is depressed,
total T4 and T3 levels will go down. An
increase in TBG due to higher levels of
total thyroid hormone. However note
that the small ratio of T3 and T4 remain
unbound to TBG (0.05% of T4 and
0.5% of T3), the so-called free fraction
(1987,Alen et al), Thyroid Stimulating
Hormone (TSH) levels. Typically
increase in hypothyroidism, the thyroid
is not secreting adequate concentration
of T4, and in an attempt to stimulate the
thyroid, the pituitary gland secretes
excess TSH. So TSH is HIGH in
hypothyroidism. The opposite is
observed in hyperthyroidism: the
excess thyroid hormone in circulation
acts back on the pituitary to suppress
TSH production. in hyperthyroidism
TSH is LOW.
Figure (5) showed that, nandrolone
treatment induced a significant
elevation in serum cholesterol levels all
over the experimental groups.
When the thyroid hormones level slows
down (hypothyroidism), it also slows
down the body ability to process
cholesterol. This processing lag is
largely explained by a decreasing in the
activity and number of what are known
as(low-density
lipoproteins) LDL receptors and
apolipoprotein B (apo A) in liver LDL
receptors help remove bad cholesterol
0
0.5
1
1.5
2
2.5
3
3.5
control 5mg/kg 10mg/kg
concentration of T4
concentration of AAS(mg/kg)
* *
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
24
ISSN 2072-3875
from the body; when the number of
receptors decreases, LDL accumulates
in the bloodstream, acting to increase
both LDL and total cholesterol
levels.The high-density lipoprotein
(HDL) levels are normal or even
elevated in severe hypothyroidism
because of decreased activity of
cholesteryl-ester transfer protein
(CETP) and hepatic lipase (HL), which
are enzymes regulated by thyroid
hormones. The low activity of CETP
and more specifically of hepatic lipase,
results in decrease transport of
cholesteryl esters from HDL(2)to very
low-density lipoproteins (VLDL) and
intermediate low-density lipoprotein
(IDL), and reduce transport of HDL(2)
to HDL(3). Moreover, hypothyroidism
increases the oxidation of plasma
cholesterol mainly because of an altered
pattern of binding and to the increased
levels of total cholesterol, which
presents a substrate for the oxidative
stress. Overt hypothyroidism is
characterized by hypercholesterolemia
and a marked increase in low-density
lipoproteins (LDL)) because of a
reduced fractional clearance of LDL by
a decrease number of LDL receptors in
the liver (2002,Duntase) On the other
hand , nandrolone has higher ability to
induce hepatic triglyceride lipase(
HTGL) which may explain our results
in which nandrolone has an increasing,
effect on LDL and reduced effect on
HDL levels. It is worth mentioned that,
the marked increased levels of total
cholesterol (2003,Maron) which
presents a substrate for the oxidative
stress.
Concerning the effect of nandrolone
on serum oxidants/ antioxidants status
(figure 6 and 7), statistical analysis
revealed a significant increase of MDA
and a significant decrease of GSH
contents (p ? 0.05) compared to control
.
Figure(5)Changes in total cholesterol level (mg/dl)in treatment groups .values are
M± S.E.,* P?0.05 compared to control group.
0
20
40
60
80
100
control 5mg/kg 10mg/kg
concentration of total
cholesterol
concentration of AAS(mg/kg)
* *
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
25
ISSN 2072-3875
Figure(6)Changes in MDA concentration(mmol/L) in treatment groups .values
are M± S.E.,* P?0.05 compared to control group
The main function of thyroid hormone
within physiological ranges is to
regulate and enhance metabolic
reaction and oxygen consumption of
different cells of the body. ROS which
are the by-products of tissue
metabolism are normally treated by
physiological antioxidants.
Previous study showed that both
hyper- and hypothyroidism are
associated with increased oxidative
stress. In the new study
with hypothyroid patients it was clearly
shown that their antioxidant enzyme
systems of their bodies were working
overtime trying to keep up with the
excessive production of free radicals
induced by their hypothyroid situation
of metabolic inefficiency
(2012,Richards,).
Oxidative stress may result from
either over-production of reactive
oxygen species (ROS) or from failure
of the antioxidant defense systems
(2011,Babu, et al,). ROS have a high
reactivity potential, therefore they are
toxic and can due to oxidative damage
in cellular macromolecules like lipids,
proteins, , and DNA and might result in
cell death by necrosis or apoptosis.(
1999, Gamaley, and Klyubin )
Concerning the effect of treatment
with ND our results of the present study
revealed hypothyroidism situation
induce oxidative stress by increase
malondialdehyde (MDA) level as a
product of polyunsaturated fatty acids
oxidation and decrease glutathione
(GSH) level in the serum (figure 6,7)
,this is agreed with data reported by
Tugyan et al.(2012). Dariyerli et al.
(2004) showed that there is no
statistically significant difference found
between hypothyroid and control
groups in the lipid peroxidation
indicator MDA. The results of Yilmaz
et al. (2003) reported increased plasma,
muscle and liver MDA levels in
hypothyroid rats contradict our
findings. This conflicting findings are
thought to be due to different study
materials in several animal models .
0
2
4
6
8
10
12
control 5mg/kg 10mg/kg
MDA level
concentration of AAS(mg/kg)
*
*
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
26
ISSN 2072-3875
Figure(7)Changes in GSH concentration(mmol/L) in treatment groups .values are
M± S.E.,* P?0.05 compared to control group.
Recent stydies have show
Hypothyroidism-associated oxidative
stress is the consequence of both
increased production of free radicals
and decrease ability of the antioxidative
defense.( 2004,Das and Chainy;
2005,Sarandol ,et al,) Hypothyroidisminduced
dysfunction of the respiratory
chain in the mitochondria due to
accelerated production of free radicals
(i.e., hydrogen peroxide, superoxide
anion, and hydroxyl radical as well as
lipid peroxides), which consequently
dues to oxidative stress (OS).
(1997,Venditti et al; 2003,Yilmaz et al)
Metabolic disorder from autoimmunebased
hypothyroidism can also increase
oxidative stress.( 2008,Carmeli et al)
In conclusion our data indicate that
androgenic anabolic steroid exerts
direct actions on the thyroid gland and
in the peripheral metabolism of thyroid
hormones and might lead to thyroid
dysfunction and induced oxidative
stress.
References :
AbdAllah,M.A.(2013): Effect of
bilateral orchidectomy on thyroid
gland structure of adult albino rats
and the role of Nandrolone
Decanoate administration Journal
of American Science;9(12).
Alen, M.; Rahkila, P.; Reinila, M. and
Vihko, R. ( 1987) : Androgenicanabolic
steroid effects on serum
thyroid, pituitary and steroid
hormones in athletes. Am J Sports
Med. Jul-Aug;15(4):357-61
Arafah, B.M.(1994). Decreased
levothyroxine requirement in
women with hypothyroidism
during androgen therapy for breast
cancer. Annals of Internal
Medicine , 121 247–251.
Attardi, B.J., Pageb, S.T. ; Hild, S.A. ;
Christopherand , C.C. and
Matsumoto, A.M. ( 2010):.
Mechanism of action of bolandiol
(19-nortestosterone), a unique ana
bolicsteroid with androgenic,
estrogenic and progestational
activities. J. of Steroid
0
10
20
30
40
50
60
70
control 5mg/kg 10mg/kg
GSH level
concentration of AAS
*
*
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
27
ISSN 2072-3875
Biochemistry and Molecular
Biology, 118: 151-161.
Babu, K., Jayaraaj ,I.A.,and Prabhakar,
J. (2011): Effect of Abnormal
thyroid hormone changes in lipid
peroxidation and Antioxidant
imbalance in Hypothyroid and
Hyperthyroid patients, Int J Biol
Med Res.; 2(4): 1122 – 1126.
Bahrke, M.S .and Yesalis, C.E. (2004):
.Abuse of anabolic androgenic
steroids and related substances in
sport and exercise. Curr Opin
Pharmacol;4:614–20.
Balsam, A. Sexton, F.C. (1975):
Increased metabolism of
iodothyronines in the rat after
short-term cold adaptation.
Endocrinology 97:385,.
Banu, S. K., P. GovindarjuLu, and.
Aruldhias M. M.(2002):
Testosterone and estradiol
differentially regulate TSHinduced
thyrocyte proliferation in
immature and adult rats. Steroids
67:573-579
Bermudez, D.S.; Skotko ,J.P.; Ohta, Y.
; Boggs, A.S. and Iguchi
,T.(2011): Sex steroid and thyroid
hormone receptor expression in
the thyroid of American Alligator
(Alligator Mississippiensis)
during different life stages. J
Morphology ; 272:698-703.
Bisschop ,P. H ; Toorians ,A. W. ;
Endert,E. ; Wiersinga, W.M.
;Gooren,L.J. and Fliers , E
(2006): The effects of sex-steroid
administration on the pituitary–
thyroid axis in transsexuals
Journal of Endocrinology ;155
11–16.
Borges, P. P., Curry, F. H. Pazos-
Moura, C. C. and MouRA, E. G..(
1998.): Effect of testosterone
propionate treatment on
thyrotropin secretion of young and
old rats in vitro. Life Sci. 62:2035-
2043.
Carmeli, E.; Bachar, A.; Barchad, S.;
Morad, M., and Merrick, J. (
2008.): Antioxidant status in the
serum of persons with intellectual
disability and hypothyroidism: A
pilot study. Res. Development.
Disab., 29:431-438.
Chrousos, G. P.( 2006):. The gonadal
hormones and inhibitors. In: Basic
and Clinical Pharmacology (Ed.
B. G. Katzung). McGraw-Hill
Professional, New York, USA. pp.
674-676.
Dariyerli, N.; Toplan, S.; Akyolcu,
M.C.; Hatemi, H. and Yigit, G.
(2004): Erythrocyte
osmotic,fragility and oxidative
stress in experimental
hypothyroidism. Endocrine; 25: 1-
5.
Das, K. and Chainy, G.B. (2004)
.Thyroid hormone influences
antioxidant defense system in
adult rat brain. Neurochem. Res.,
29(9):1755-1766.
DeyssiG, R., and Weissel , M. (1993):
Ingestion of androgenic-anabolic
steroids induces mild thyroidal
impairment in male bodybuilders.
J. Clin. Endocr. Metab. 76:1069-
1071.
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
28
ISSN 2072-3875
Duntase,L.H.(2002). Thyroid disease
and lipids. Thyroid;12(4):287-93.
Gamaley, I.A. and Klyubin, I.V.
(1999):. Roles of reactive oxygen
species: signaling and regulation
of cellular functions. Intern. Rev.
Cytol., 188:203-255,.
Guerrero, A.;Pamplona, R.; Postero-
Otin, M.; Barja, G., and Lopez-
Torres, M. (1999): Effect of
thyroid status onnlipid
composition and peroxidation in
the mouse liver. Free. Rad. Biol.
Med., 26:73-80, 1999.
Hickson, R.C.; Czerwinski S.M., and
Falduto, M.T.( 1990): . Young AE
Glucocorticoid antagonism by
exercise and androgenic-anabolic
steroids. Med. Sci. Sports Exerc.,
22: 331-340.
Huh, K.; Kwon, T.H.; Kim, J.S.; Park,
J.M. (1998): Role of the hepatic
xanthine oxidase in thyroid
dysfunction: Effect of thyroid
hormones in oxidative stress in rat
liver. Arch. Pharm. Res., 21, 236–
249.
Hulbert,A. (2000): Thyroid hormones
and their effects: a new
perspective. Biological Reviews
of the Cambridge Philosophical
Society Vol. 75, No. 4, pp 519-
621
Li, J. and Al-Azzawi, F.( 2009):.
Mechanism of androgen. receptor
action. Maturitas, 63: 142-148.
Maron, B.J.(2003): Sudden death in
young athletes. N. Engl. J. Med.,
349(11): 1064-75.
Moron,M.S.;epirre,J.W.and
Mannervik,B.(1979):Levels of
Glutathion reductase and
glutathione S-transferase activities
in rat lung and liver; Biochemical
et Biophysical Acta; 582:67-78.
Nishiki K, Erecinska, M.; Wilson,
D.F.and Cooper, S.(1978):
Evaluation of oxidative
phosphorylation in hearts from
euthyroid, hypothyroid, and
hyperthyroid rats.Am J Physiol;
235:212-219.
Pasupathi,P .and Latha, R. (2011) : Free
Radical Activity and Antioxidant
Defense Mechanisms in Patients
with Hypothyroidism ; Thyroid
Science 3(12):CLS1-6
Peepre1,K.; Deshpandey, U. and
Choudhary; P. S .(2014): Role of
Antioxidants on Thyroid
Hormones in Wister Rats.
International Journal of Science
and Research (IJSR), 3 (1).
Richards,B.J.(2012): Hypothyroidism
induce antioxidants efficiency,
Board Certified Clinical
Nutritionist; 4.
Rodrigo, S.; Michelle, F. P.; Elen, M.
A.; Joslt, C.; Nascimento , H. M.;
Rosenthal , D. and Carvalho ,D. P.
(2006). Chronic Administration of
Anabolic Androgenic Steroid
Alters Murine Thyroid Function ,
Medicine & Science in Sports &
Exercise,38(2) ,257-261
Russell T. and Joffe, M.D .(2011):
Hormone treatment of depression
, Dialogues Clin Neurosci.; 13(1):
127–138.
Salas-Ramirez, K. Y.; Montalto, P. R.
and Sisk, C. L. ( 2008): Anabolic
androgenic steroids differentially
Euphrates Journal of Agriculture Science-6 (4): 16-29 , (2014) Rahim &Abde-Allh
29
ISSN 2072-3875
affect social behaviors in
adolescent and adult male Syrian
hamsters. Horm Behav. 53:378-
385.
Sarandol, E., Tas, S., Dirican, M., and
Serdar, Z. (2005): .Oxidative
stress and serum paraoxonase
activity inexperimental
hypothyroidism: Effect of vitamin
E supplementation. Cell Biochem.
Funct., 23(1):1-8,
Sarne,D.M.D.(2010). Effects of the
Environment, Chemicals and
Drugs on Thyroid Function.
Shahidi, N.T. (2001) : A Review of the
Chemistry, Biological Action and
clinical applications of . anabolicandrogenic
steroids. Clinical
therapeutics, 23(9): 1355-1390.
Sies, H.(1986): Biochemistry of
oxidative stress. Angew Chem Int
25: 1058-1071,
Thiblin, I. and Petersson, A. (2005):
Pharmacoepidemiology of
anabolic androgenic steroids: a
review. Fundam Clin
Pharmacol;19:27–44.
Tugyan, K., S.; Ozbal, S.; Cilaker, M. ;
Kiray,. C.; Pekcetin, B.; Ugur
Ergur and Kumral,A. (2012):
Neuroprotective effect of
Erythropoietin on Nandrolone
Decanoate-induced brain injury in
rats. Neuroscience Letters,
Available online 10 October .
Venditti, P.; Balestrieri, M.; Di Meo, S.
and De Leo, T. (1997): Effect of
thyroid state on lipid peroxidation,
antioxidant defenses, and
susceptibility to oxidative stress in
rat tissues. J. Endocrin.,
155(1):151-157.
Yilmaz, S.; Ozan, S.; Benzer, F. and
Canatan, H. (2003): Oxidative
damage and antioxidant enzyme
activities in experimental
hypothyroidism. Cell Biochem.
Funct., 21(4):325-330