journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
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protective effect of panax ginseng on
flutamide-induced spermatogenesis
impairment in adult rats
shaima ahmed rahim
department of biology. college of science for woman babylon university ,iraq
shaima.hilla@yahoo.com
abstract
flutamide is non-steriodal ,antiandrogenic drug,commonly used in the treatmeant of advanced
prostate cancer, acne and hirsutism, this drug may induce suppression spermatogenesis. this study
aims to evaluate of the protective effect of panax ginseng roots against flutamide-induced testicular
toxicity in adult male rats . the aimals were divided into six groups: first group as a control second
group were given orally flutamide at dose (25 mg/kg b.wt) for seven days third and fourth groups were
injected intrapretonialy with p.ginseng extract at dose of( 200,400) mg/kg/day for thirty five days ,fifth
group were given orally flutamide (25 mg/kgb.wt) for seven days then were injected intrapretonialy
p.ginseng extract at dose (200 mg/kg/day) for thirty five days ,and sixth group were given orally
flutamide (25 mg/kgb.wt) for seven days then were injected intrapretonialy p.ginseng extract at dose
(400 mg/kg/day) for thirty five days. all groups were treated daily, twenty four hrs after last treatment
all rats were euthanized , tissue sampling of the testis was done after the mentioned time for each
group, tissue slices were stained by h&e technique.gonadosomatic index, histomorphometrical and
histopathological analysis of the testis was carried out , male rats exposed to flutamide had significant
reduction in spermatogenesis related- parameters included : diameter of seminiferous tubules,
epithelial height of seminiferous tubules , germ cells count ,sertoli cells count , johnsen’s score,
tubular differentiation index (tdi), and spermiogenesis index (spi) ) compared with the control and
p.ginseng treated groups , flutamide induced histopathological changes in the testis , water extract of p.
ginseng manifested marked improvement in spermatogenesis as well as histopathological alteration.
the results of this current study suggest that the testicular changes induced by flutamide were
significantly recovered by panax ginseng roots
.key words: panax ginseng flutamide,spermatogenesis, testis.
الخلاصة :
الفلوتامايد مضاد اندروجيني ،لاسيتيرويدي يستخدم عادة في علاج سرطان البروستات المتقدم، حب الشباب والشعرانية، وهذا
الدواء قد يسبب اعاقة لعملية نشاة النطفة. تهدف هذه الدراسة إلى تقييم الاثر الوقائي لجذور نبات الجنسينغ ضد تسمم الخصية التي
يسببها الفلوتامايد لدى ذكورالجرذان البالغة. تم تقسيم الحيوانات إلى ست مجاميع: المجموعة الأولى كمجموعة سيطرة ؛ أعطيت
لمدة سبعة أيام؛ تم حقن المجموعة الثالثة والرابعة (b.wt المجموعة الثانية الفلوتامايد عن طريق الفم بجرعة ( 25 ملغم / كغم
بمستخلص الجينسينغ بجرعة ( 200,400 ) ملغم / كغم / يوم في التجويف البريتوني لمدة خمسة وثلاثين يوما، وأعطيت المجموعة
لمدة سبعة أيام ثم حقنت بمستخلص نبات الجينسينغ بجرعة (b.wt الخامسة الفلوتامايد عن طريق الفم بجرعة ( 25 ملغم /كغم
200 ملغم / كغم / يوم) في التجويف البريتوني لخمسة وثلاثين يوما، وأعطيت المجموعة السادسة الفلوتامايد عن طريق الفم )
لمدة سبعة أيام ثم حقنت بمستخلص نبات الجينسينغ بجرعة ( 400 ملغم / كغم / يوم) في التجويف (b.wt بجرعة ( 25 ملغ / كغم
البريتوني لخمسة وثلاثين يوما . عوملت كل المجاميع يوميا ، تم تخدير الحيوانات بعد أربع وعشرون ساعة من اخر جرعة ، وقد
تم أخذ عينات من انسجة الخصى لكل مجموعة، و صبغت شرائح الأنسجة بتقنية الهيماتوكسيلين – ايوسين , و قد تم تقدير
اظهرت ذكور الجرذان ، histomorphometrical and histopathological analysis و gonadosomatic index
المتعرضة للفلوتامايد انخفاض معنوي في المعايير المرتبطة بعملية نشاة النطفة و التي تشمل : اقطار النبيبات المنوية ، ارتفاع
ومؤشر ،(tdi) بطانة النبيبات المنوية ،اعداد الخلايا الجرثومية ، اعداد خلايا سرتولي ، مؤشرجونسن ، ومؤشر تمايز النبيبات
بالمقارنة مع مجموعة السيطرة ومجموعة الحيوانات المعاملة بالجينسينغ ، اظهرالمستخلص المائي لنبات ((spi) حؤول النطفة
الجينسينغ تحسن ملحوظ في عملية نشاة النطفة بالاضافة الى التبدلات المرضية النسجية التي سببتها المعاملة بالفلوتامايد . تشير
نتائج هذه الدراسة الحالية الى أن التغييرات الخصوية الناجمة عن الفلوتامايد صححت معنويا بوساطة جذور نبات الجينسينغ .
الكلمات المفتاحية : باناكس جينسينغ , فلوتامايد, عملية نشاة النطفة , الخصية.
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2411
introduction
environmental, anti-androgenic compounds have been recognized as endocrine
disruptors because of their hormone-like activities. antiandrogenic chemicals have
the potential to interfere with male reproductive development and function in human
and animals. the endocrine disruptors are thought to act via many mechanisms, such
as by decreasing androgen synthesis, exerting effects on the pituitary-gonadal axis
and/or blocking the androgen receptor. the consequences of these actions may cause
abnormal hormonal regulation and gene expression (sharpe, 2006, metzdorff et al.,
2007).
flutamide (4 -nitro-3 -trifluoro-methylisobutyranilide) is a potent non-steroidal
androgen receptor antagonist (kassim et al,1997)..flutamide acts by inhibiting the
uptake and/or binding of dihydrotestosterone to the target cell receptor, thus
interfering with androgen action. flutamide is well absorbed orally and extensively
and rapidly metabolized to its active metabolite, 2-hydroxyflutamide, and excreted
almost entirely by the kidneys (xu and li, 1998). in male patients who display
androgen excess, flutamide is used therapeutically to treat androgen dependent
prostate cancer, where it prevents androgens from binding to androgen receptors in
the prostatic gland and in prostatic cancer cells (javier et al., 2001, zhang et al., 2005).
it is also used in young women who suffer increased androgen production, such as
hirsutism, acne and seborrhea (thiboutot & chen, 2003, sahin & kelestimur, 2004).
flutamide is regarded as a model antiandrogen and in experimental studies it is
often used as a positive control in screening assays used for the identification of
endocrine disruptors (o’connor et al., 1998). several studies demonstrated the effects
of short-term androgen blockage induced by the administration of flutamide to
immature or mature males(maschio etal,2010, vo etal,2009). pre- and postnatal
exposure of rats to flutamide alter androgen-dependent reproductive development
and function (kassim e tal,1997). it has been indicated that exposure of rats to
flutamide caused a dysregulation in expression of hypothalamus/ pituitary hormone
genes and consequently this may affect gonadotropin release and induce an overexpression
of testicular steroidogenic enzyme genes( ohsako etal,2003).
a number of studies are conducted on the use of herbal plants within the treatment
of infertility. seeing as these plants typically have low side effects, their
administration can be an appropriate approach.
panax ginseng, a traditional multipurpose herb in asia, has become the world’s
most popular herbal supplements in recent years. p.ginseng has a variety of beneficial
biological processes that include anti-carcinogenic, anti-diabetic and antiinflammatory
effects,anti-stress, anti-aging, antioxidant and gonadal function
improvement as well as cardiovascular-and neuro-protection, (jung et al,2005).
the herb is used in its entirety and prepared as tea, powder, or capsules. the herb
contains saponins or soap like materials that have been named with various numbers
and letters, such as rg1 with a root said to have a composition similar to that of
steroids (liu e tal., 1995). the herb is a deciduous perennial belonging to the family
araliaceae. the herbal root is named ginseng, because it is shaped like a man or
human body (yun, 2001). named by botanist carl meyer in (1842), the genus panax
(pan=all+axos=medicine) means cure all or a panacea in greek (gillis, 1997). the
most important part of ginseng is the root, ginseng roots contain various
pharmaceutical components ginsenosides (saponins), polyacetylenes, polyphenolic
compounds and acidic polysaccharides, and among the components, ginsenosides are
the most pharmaceutically active (kim et al,2005). until now, 38 ginsenosides are
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2412
isolated from ginseng roots, with five major ginsenosides (ginsenosides rb1, rb2, rc,
re and rg1) constituting more than 80% of the total ginsenosides (kim et al,1999).
several clinical studies indicated the beneficial effects of ginseng on the male
fertility in different animal models such as mice (yoshimura etal,1998), rabbit (kim
etal,1998), guinea pig (kim et al, 1999) and rats (tsai etal., 2003).. in addition,
human studies indicated a beneficial effect of ginseng on healthy human subjects
(salvati etal,1996) and patients (hong etal, 2002). these effects of ginseng might not
be due to changes in hormone secretion, but to direct effects of ginseng or its
ginsenoside components on the central nervous system and gonadal tissue (hong
etal,2002, murphy&lee,2002). the administration of ginseng water extract protects
testicular function( kim etal,1999), and improves sperm survival rate and quality in
guinea pigs exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (hwang etal,2004).there
is evidence to support the use of panax ginseng in the treatment of male sexual
dysfunction (hong etal,2002).
the obejective of this work is to elevate the potential protective action of panax
ginseng roots against flutamide toxicity particularly on testis of adult male rats.
materials and method
chemicals:
flutamide(tablet 250mg) was obtained from medochemic limited –mlt ciprus.
flutamide dissolved in 10ml of pure corn oil,and each 1ml contains 25 mg of
flutamide (sanchez-craido et al,1999).
preparation of aqueous extract of panax.ginseng
root powder of korean ginseng (panax ginseng ) was purchased from al-kawther
herb in hilla city -babylon , for preparation 200mg or 400mg\kg of an aqueous extract,
40 mg or 80 mg of herbaceous plant roots were added to 100ml cold water and
mixed in an electric mixture for 20 minutes. the mixture was centrifuged, and the
clear supernatant was carefully removed and kept in a refrigerator at 2–8?c as a final
extract for subsequent experimental treatments the dose was calculated according to
the animal s body weight.
animals : the study was carried out on 24 adult male albino rats weighing 200 to 300
g and obtained from the animal house laboratory, faculty of science , kufa
university and acclimatized to the facility for at least 1 week before the experiment
and kept under standard conditions, temperature 20oc, humidity 60% and 12/12-h
light/dark cycle and maintained on standard diet and free water supply ad libitum till
the end of study.
experimental design
after the period of acclimation, animals were divided into six groups with 4
animals in each as :
1) control group: animals received 1ml of distilled water orally daily for 35 days.
2) flutamide treated group: animals daily received orally dose of flutamide (25
mg/kg b.wt.) for 7 days using metallic stomach tube.
3) panax ginseng treated group: animals were injected intrapretonialy (200 mg/kg
b.wt.) daily for 35 days.
4) panax ginseng treated group: animals injected intrapretonialy (400mg/kg b.wt.)
daily for 35days .
5) flutamide +p.ginseng treated group: animals were given orally flutamide
(25mg/kg b.wt.) for 7days and then injected intrapretonialy with p. ginseng extract
(200mg/kgb.wt) for 35 days .
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2413
6) flutamide+p. ginseng treated group: animals were given orally flutamide
(25mg/kg b.wt.) for 7 days and then injected intrapretonialy with ginseng extract
(400mg/kg b.wt.) for 35 days.
gonadosomatic index (gsi)
having determined the weight of the left and right testicles of each animal, it was
also possible to calculate the gonadosomatic index (percentage of the body occupied
by the gonad) using the following formula:
gonadosomatic index (%) = [(rtw + ltw(g) / bw(g))] x 100
being: rtw = weight of right testis
ltw = weight of left testis
bw = body weight . (predes et al,2007).
histological technique:
at the end of the experiment, the rats were euthanized under general anesthesia
with diethyl ether. testes were isolated and weighed after removing any adhering
adipose and fixed in 10% formal saline for 24 hours. paraffin blocks were sectioned at
5 microns thickness by rotary microtome. the paraffin sections were then stained by
hematoxylin and eosin stains (bancroft and stevans, 1996)) and examined with the
light microscope.
analysis of spermatogenesis-related parameters
five slides were selected from each group and 10 seminiferous tubules within each
slide were evaluated for spermatogonia ,spermatocytes and the sertoli cell counts,
and the average of the different cell counts of each slide was used for the analysis.
the evaluation of all of the samples was performed at a constant magnification of 40×
with light microscopy (mclachlan etal,1996).
more than 100 horizontally sectioned seminiferous tubules per group were
analyzed to determine the spermatogenesis-related histology. all seminiferous tubules
in one histological section of the testicular specimen were evaluated and scored on a
scale of 1 to 10 using johnsen’s scoring system(johnsen, 1970). briefly, the scoring is
as follows:
s\no parameter
10 complete spermatogenesis with many spermatozoa
9 many spermatozoa present, but with a disorganized
spermatogenesis
8 only a few ( <5) spermatozoa
7 no spermatozoa, but many spermatids
6 no spermatozoa and only a few(<5) spermatids
5 no spermatozoa and spermatids but several or many
spermatocytes
4 no spermatozoa and spermatids and only a few
spermatocytes (<5)
3 spermatogonia were the only germ cells present
2 no germ cells, but sertoli cells were present
1 no cells in a tubular section
the tubular diameter of the seminiferous tubule and the height of the seminiferous
epithelium which was regarded as the distance from the basement membrane to the
tubular lumen, were measured by using an ocular micrometer calibrated with a stage
micrometer. fifty tubular profiles that were spherical or nearly spherical were chosen
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2414
randomly and measured for each group. the epithelium height was obtained within
the same tubule sections utilized to determine tubular diameter(brendtson, 2008).
for the estimation of spermatogenesis in testicular tissue, two different indices
were used. tubular differentiation index (tdi), and spermiogenesis index (spi). to
determine the tubular differentiation index, the number of seminiferous tubules that
have more than three layers of germinal cells derived from type a of spermatogonia
was calculated. to find out the spermiogenesis index, the ratio of the number of
seminiferous tubules with spermatozoids to the empty tubules was calculated
( meistrich etal,2003, shetty etal,2000).
statistical analysis the data were expressed as mean±sem statistical analysis
was performed with anova followed by post-hoc tukey multiple range tests using
the statistical package for the social sciences (spss/version 17.0) for windows. p
<0.05 were considered statistically significant .
results and discussion
spermatogenesis is the formation of mature sperms from primitive germ cells
occurring in the testis. this process is under hormonal control by hypothalamushypophysis
-gonadal axis. androgens are essential for male development and play an
indispensable role in the process of spermatogenesis. androgens act on their target
cells via an interaction with androgen receptors (ar) resulting in direct regulation of
gene expression(brinkmann et al,1999). antiandrogens block the androgen receptors
competitively by producing a different conformational change avoiding participation
of testosterone in the cellular processes. in an animal study on rats, the administration
of antiandrogen such as flutamide, results in impaired spermatogenesis and
dysfunction of accessory sex organs(bustos-obregon et al,2006).
administration of flutamide for 7 days did not result in any changes in testicular
weight represented in gonadosomatic index(gsi) figure(1), these findings are similar
to that obtained by (back etal,1977,dhar and setty,1976,yamada etal,2000) the
reason may be due to the shorter duration of study .
figure(1):gonadosomatic index (gsi) in control and treated groups , results are presented
asmean ± sem,+ p<0.05 compared to the flutamide treated group.
+ + +
+
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2415
this study showed that flutamide had destructive effects on testis tissue and
parameters related to spermatogenesis which includes :(tubular diameter,epithelial
height of seminiferous tubules , germ cell count ,sertoli cells count , johnsen’s score,
tubular differentiation index (tdi), and spermiogenesis index (spi) ) compared with
the control and treated groups figure(2),(3),(4),(5),(6),(7),(8),(9),(10), the possible
mechanism that explains these destructive effects of exposure to flutamide on
testicular structure: flutamide blocks the physiological action of testosterone at
androgenic receptor sites and/or alters androgen receptor levels (kelce et al,1997) and
consequently, causes atrophic changes to the seminiferous tubules by depressing the
function of sertoli cells. (vo et al,2009) reported the anti-androgenic effects of
flutamide to alter reproductive function, this is in concert with, our results as
flutamide disrupted germ cells of the seminiferous tubules.
+
figure(2):diameter of seminiferous tubules in
control and treated groups , results are
presented asmean ± sem ,*p<0.05 compared
to the control ,+ p<0.05 compared to the
flutamide treated group.
figure(3):epithelial height of
seminiferous tubules in control and treated
groups , results are presented asmean ±
sem ,*p<0.05 compared to the control ,+
p<0.05 compared to the flutamide treated
group.
figure(4):number of spermatogonia in
control and treated groups , results are
presented asmean ± sem ,*p<0.05
compared to the control ,+ p<0.05
compared to the flutamide treated group.
figure(5):number of spermatocytes in
control and treated groups , results are
presented asmean ± sem ,*p<0.05
compared to the control ,+ p<0.05
compared to the flutamide treated group.
*
+ +
+
*
+
+
+
*
+
+
*
+ + + +
+
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2416
figure(6):number of spermatid in
control and treated groups , results are
presented asmean ± sem ,*p<0.05
compared to the control ,+ p<0.05
compared to the flutamide treated
group.
figure(7):number of sertoli cells in
control and treated groups , results are
presented asmean ± sem ,*p<0.05
compared to the control ,+ p<0.05
compared to the flutamide treated
group.
figure(8):johnson’score in control and
treated groups , results are presented
asmean ± sem ,*p<0.05 compared to the
control ,+ p<0.05 compared to the
flutamide treated group.
figure(9):tubular differentiation
index(tdi) in control and treated groups ,
results are presented asmean ±
sem ,*p<0.05 compared to the control ,+
p<0.05 compared to the flutamide treated
group
.
*
+
+ +
*
+
+
+
+
*
+
+ +
*
+ + +
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2417
it is believed that flutamide disrupts the function of the hypothalamo-pituitarygonadal
(hpg) axis (kassim et al,1997). this could be the reason for the increase in
lh of flutamide treatment, decreased testosterone level is usually accompanied with
increased lh production by the anterior pituitary gland. hence,this increase in
luteinizing hormone resulted from the decreased testosterone feedback. it has been
reported by (cheng etal,2008) that testosterone plays an important role in maintaining
quantitatively normal spermatogenesis. and decreased testosterone was accompanied
with disrupted spermatogenesis. furthermore, (ohsako et al ,2003) reported that
subacute flutamide administration for 6 days first affected hypothalamus/pituitary
hormone gene expression resulting in altered testicular steroidogenesis and decreased
sperm production. flutamide administration has also been found to affect the initial
step of spermatogenesis and cause a reduced sperm count due to inhibition of
differentiation of spermatogonia to spermatocytes (viguier-martinez etal, 1985,
chandolia,et al,1991a,b).
on the idea of the results of present experiment it is concluded that the testicular
atrophy as evidenced by decrease in diameter of seminiferous tubules, thickness of
germinal epithelial tissue as a result of the toxic effect of the antiandrogen such as
flutamide on the testes in generally and seminiferous tubule inparticular.
histological and histomorphometrical examination of the testis by h&e technique
disclosed that flutamide treated group compared with those of control group: severe
epithelial degeneration and atrophy of most seminiferous tubules with the loss of
sperm and additionally showed significant decrease in means of johnsen’s score,
tubular differentiation index (tdi), and spermiogenesis index (spi) a number of
these changes are shown in figures (8),(9),(10) , whereas there have been no
histopathological changes in the control and ginseng 200,400mg\kg treated groups
and (flutamide +ginseng 200 ,400mg\kg) treated groups .
figure(10):spermiogenesis index (si) in control and treated groups , results are presented
asmean ± sem ,*p<0.05 compared to the control ,+ p<0.05 compared to the flutamide
treated group.
*
+ + +
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2418
photomicrographs showing sections of testes administered:control(a),flutamide(b),
ginseng200mg\kg(c),ginseng400mg\kg(d),flutamide+ginseng200mg\kg(e),flutamide+ginseng
400mg\kg(f), stained with h&e at mannification x200, the cellular structure of the
seminiferous tubules was almost normal in appearance for all groups . however,flutamide
treatmeant induced sever epithelial degeneration ,atrophy of most seminiferous tubules ,loss of
sperm and reduction in the number of spermatogenic cells and epithelial height of seminiferous
tubules.
panax ginseng was known to have protective and therapeutic effects against the
testicular atrophy and other damages induced the most potent environmental
pollutants toxic to reproductive organs (kim etal,1999). ginsenosides are triterpenoid
saponins that structurally resemble the steroid hormones. thus, it’s tempting to invest
that the effects of ginsenosides on sexual function and spermatogenesis are a result of
activation of steroid receptors. androgens are sex steroids that are essential for the
development and maintenance of male sexual characteristics, and regulate traditional
a b
c d
e
f
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
2419
spermatogenesis (leung and wong,2013). androgen receptor (ar) is abundantly
expressed in male genital tissues and in spermatozoa (solakidi etal,2005).
our data showed that there was statistically significant increase in testis weight
represented in gonadosomatic index in (ginseng 200,400 mg\kg) treated groups
compared with control group and (flutamide + ginseng 200,400 mg\kg )treated
groups compared with flutamide group figure(1), these findings are like that
obtained by(moon and park,1970) showed that ginseng increased gonadal weight in
young male and female rats receiving ginseng alcohol extract, in addition,
(yamamoto etal,1977) showed that ginseng could stimulate protein synthesis through
activation of dna-dependent rna -polymerase with increasing the testicular nucleic
acid content, indicating the stimulatory effect of ginseng on spermatogenesis. where
the herb was reported to promote the growth of the testis and spermatogenesis in
rabbits (brekhman,1964).
the obtained results from figure(2),(3),(4),(5),(6),(7) revealed significant changes
in parameters related to spermatogenesis, which includes : tubular diameter,epithelial
height of seminiferous tubules , germ cell count ,sertoli cells count in (ginseng 200,
400mg/kg ) groups compared with control group, also (flutamide + ginseng 200,400
mg\kg ) treated groups showed significant increase in these parameters compared with
flutamide group , these spermatogenic effects of. ginseng might be due to the
combined effect of its many components , ginsenosides, (saponins) polyphenol and
minerals (park etal,2006). among the components, ginsenosides are the most
pharmaceutically active (kim etal,2005). (salvati etal, 1996) suggested that
ginsenosides might have an effect at the different levels of the hypothalamus
pituitary-testis axis, where it can stimulate hypothalamic gonadotropins-releasing
hormone (gnrh) release, stimulate pituitary gonadotropins release and stimulate
synthesis and secretion of testicular androgens. (renyong and hong,1986) reported
that the lh secretion of adenohypophysis incubated with ginseng (g) or pantocrine
(p) significantly increased. furthermore (tsai etal,2003) found that ginsenosides rb1
in a dose-dependent manner increased the release of lh from both hemi-anterior
pituitary tissue and dihydrotestosterone (dht), suggesting that ginsenosides rb1
increases lh secretion by acting directly on the anterior pituitary cells. in addition,
(renyong and hong,1986)) and (tsai etal,2003) showed that ginsenosides increase
lh secretion by acting directly on anterior pituitary cells, coinciding with
(hafez,1976), lh binds to a cell surface receptor in interstitial cells leading to
activation of adenyl cyclase resulting in generation of camp and subsequent
activation of protein kinase. this ultimately results in stimulation of steroidogenesis
and production of testosterone.
in our study, histopathological changes appeared in the testes of rats treated with
ginseng revealed statistically significant increase in johnsen’s score figure(8), that
offers a convenient and rapid method for registration of spermatogenesis
(johnsen’s,1970), thus an increase in the mean of johnsen score is an indirect
evidence of improvement in the sperm count (iftikar etal,2014),also , increase in
tubular differentiation index (tdi), and spermiogenesis index (spi) was observed
after ginseng treatment figure(9),(10), may be due to activated spermatogenesis,
hyperplasia of the epithelial lining which could be attributed to the effect of the
testosterone hormone (pineda and dooly,2003). (fahim etal,1982) found a significant
increase in blood testosterone level in rats treated with purified panax ginseng 1% and
5% in diet for 60 days. moreover, (salvati etal ,1996) observed an increase in plasma
total and free testosterone, dihydrotestosterone, fsh, and lh levels with a decrease in
prolactin (prl) in patients treated with 4 gm/oss panax ginseng extract for 3 months.
journal of babylon university/pure and applied sciences/ no.(9)/ vol.(22): 2014
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the stimulatory effect of ginseng on pituitary gonadotropins release may play a role in
the process of spermatogenesis, where gonadotropic control of spermatogenesis
involves lh stimulation of testosterone secretion by interstitial cells into the tissue
surrounding the seminiferous tubules. fsh stimulate androgen binding protein (abp)
production by sertoli cells, and transport of testosterone into the tubular lumen and
then to the germ cells, where it interacts with a specific cytoplasmic receptor protein
(cr) and stimulates the metabolic activities and maturation of germ cells
(hafez,1976).(jang etal ,2012) reported that administration of ethanol plus red
ginseng extract appeared to minimize the negative effects of ethanol toxicity on male
fertility. this is in concert with the findings from this study as panax ginseng
ameliorated the toxic effects of flutamide on the testis .
from our present data it can be concluded that alteration of testis structure and
histopathology induced by flutamide toxicity could be improved in animals after
receiving panax ginseng roots . this study shows that treatment of panax ginseng
after treated with flutamide has therapeutic and protective role.
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