OJHAS Vol. 9, Issue 1:
|The effects of sildenafil ciltrate on the lateral geniculate body of adult Wistar rats (Rattus norvegicus) -
A histological study
Senior lecturer, Department of Anatomy,
School of Basic Medical Sciences,
College of Medical Sciences, University of Benin,
Benin City, Edo State, Nigeria,
Lecturer, School of Nursing, University of Benin Teaching Hospital, Benin City.
Address For Correspondence
Senior lecturer, Department of Anatomy,
School of Basic Medical Sciences,
College of Medical Sciences, University of Benin,
Benin City, Edo State, Nigeria.
Eweka AO, Eweka A. The effects of sildenafil ciltrate on the lateral geniculate body of adult Wistar rats (Rattus norvegicus)- A histological study. Online J Health Allied Scs.
Submitted: Feb 6, 2010;
Apr 6, 2010; Published: Jul 30, 2010
The histological effect
of oral administration of sildenafil citrate (Viagra), commonly used
as an aphrodisiac and for the treatment of erectile dysfunction on one
of the visual relay centres namely the lateral geniculate body (LGB)
of adult Wistar rat was carefully studied. The rats of both sexes
average weight of 202g were randomly assigned into three treatment
and control (n=6) groups. The rats in the treatment groups ‘A’,
‘B’ and ‘C’ received respectively, 0.25mg/kg, 0.70mg/kg and
1.43mg/kg body weight of sildenafil citrate base dissolved in distilled
water daily for 30 days, through orogastric feeding tube, while that
of the control group D, received equal volume of distilled water daily
during the period of the experiment. The rats were fed with growers’
mash obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State, Nigeria
and were given water liberally. The rats were sacrificed on day
of the experiment. The lateral geniculate body (LGB) was carefully
out and quickly fixed in 10% formal saline for histological studies.
The histological findings after H&E method indicated that the
section of the lateral geniculate body (LGB) showed some varying degree
of reduced cellular population based on its sparse distribution,
changes, cellular hypertrophy, and intercellular vacuolations appearing
in the stroma. Varying dosage and long administration of sildenafil
citrate may have some deleterious effects on the neurons of the
visual relay centre and this may probably have some adverse effects
on visual sensibilities by its deleterious effects on the cells of the
lateral geniculate body (LGB) of adult Wistar rats. It is therefore
recommended that further studies aimed at corroborating these
be carried out.
Key Words: Sildenafil
citrate, lateral geniculate body, decreased cellular population,
cellular hypertrophy, vacuolations, Wistar rats
Erectile dysfunction (ED or "male impotence") is a sexual
dysfunction characterized by the inability to develop or maintain an
erection of the penis sufficient for satisfactory sexual performance
(1) and is indicated when an erection is consistently difficult or
to produce, despite arousal.(2) There are various and often multiple
underlying causes, some of which are treatable medical conditions such
as cardiovascular disease and diabetes, neurological problems (for
trauma from prostatectomy surgery), hormonal insufficiencies
and drug side effects or psychological. It is important to realize that
erectile dysfunction can signal underlying risk for cardiovascular
disease.(3) ED is a serious medical and social problem which occurs in 10%-52%
in men and 25%-63% in women.(4)
An understanding of the physiological mechanism of erection has led
to the development of new oral therapies for erectile dysfunction that
target different sites in the sexual arousal process. Apomorphine
the arousal center of the brain. Phentolamine increases penile blood
flow. Sildenafil enhances the action of nitric oxide, an endothelial-derived
vasodilator and smooth muscle relaxant. These developments constitute a
significant advance in a much-neglected area of male medicine.(5)
Sildenafil citrate is widely used as an effective and safe oral
for erectile dysfunction of various etiologies.(6) It is a potent and
selective inhibitor of phosphodiesterase type 5 enzymes that acts to
break down cyclic guanosine monophosphate (cGMP).(7) Accumulation of cGMP inhibits the degradation of nitric oxide that is responsible for
smooth muscle relaxation within the corpora cavernosa. Nitric oxide
is released by intracavernous nonadrenergic noncholinergic nerve
not only following a central or local erectogenic stimulus but also
during rapid eye movement (REM) sleep.(8) Psychogenic erectile
(ED) patients are excellent candidates for sildenafil citrate therapy
due to the intact neurovascular pathway. Nevertheless, the drug has
been reported to be effective only in about 78% of patients with
ED.(9) It is likely that performance anxiety and sympathetic overtone
are the cause of this unresponsiveness to sildenafil citrate during
awakening, though data supporting this assumption are lacking.(10)
The drug has been found to be effective and well tolerated in men
with mild to moderate erectile dysfunction of no clinically
identifiable organic cause.(11)
the presence of PDE5 in choroidal and retinal vessels sildenafil citrate
increase choroidal blood flow and cause vasodilatation of the retinal
vasculature. The most common symptoms are a blue tinge to vision and
an increased sensitivity to light.(12) Adverse effects include
visual and retinal disturbances, dizziness and pupil-sparing third nerve
palsy.(13) It has been reported that Sildenafil citrate significantly
improves nocturnal penile erections in sildenafil non-responding
with psychogenic erectile dysfunction.(14) Several pharmacological
and physiological properties of sildenafil have been described.(15-18)
In Nigeria, most individuals often use sildenafil citrate
for sexual arousal. There is a growing apprehension that it could be
harmful or injurious to the body. Though sildenafil is currently being
used to treat erectile dysfunction in patients with multiple sclerosis,
Parkinson disease, multisystem atrophy, and spinal cord injury by
their neurologically related erectile dysfunction, conversely, it has
been implicated in a number of neurological problems, such as
hemorrhage, migraine, seizure, transient global amnesia, nonarteritic
anterior ischemic optic neuropathy, macular degeneration, branch retinal
artery occlusion, and ocular muscle palsies. Although sildenafil shows some
promise as a therapeutic agent in selected neurological disorders, well-designed
clinical trials are needed before the agent can be recommended for use in any
lateral geniculate body and superior colliculus constitute the intracranial
visual relay centres. The Lateral geniculate body in mammals is
as part of the thalamic nuclei for processing visual information.(20)
In rats the Lateral geniculate body receives input from the geniculate leaflet,
which participates in the regulation of circadian function through its
projection to the circadian pacemaker of the hypothalamus.(21)
of sildenafil citrate on the intracranial visual relay centre may not have been
documented, but there have been reports that it may be implicated in varied
symptoms of dizziness, headache, flushing, dyspepsia, nasal congestion and
impaired vision, including photophobia and blurred vision, severe hypotension,
myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased
intraocular pressure and sudden hearing loss.(22,23)
Some sildenafil users have complained
of seeing everything tinted blue (cyanopsia).(24)
2005, the U.S. Food and Drug Administration found that sildenafil could
lead to vision impairment in rare cases (25), and a number of studies
have linked sildenafil use with nonarteritic anterior ischemic optic
This work was
performed in order to investigate potential histological effects of
sildenafil citrate on the lateral geniculate body of adult Wistar rats.
Twenty-four (24) adult Wistar rats of both sexes with average weight
of 202g were randomly assigned into four groups A, B, C and D of (n=6)
in each group. Groups A, B, and C of (n=18) serves as treatments groups
while group D (n=-6) was the control. The rats were obtained and
in the Animal holdings of the Department of Anatomy, School of Basic
Medical Sciences, University of Benin, Benin city, Nigeria. They were
fed with growers’ mash obtained from Edo feed and flour mill limited,
Ewu, Edo state, and were given water liberally. The rats were
allowed to gain maximum acclimatization before the actual commencement
of the experiment. The sildenafil citrate tablets were obtained from
the University of Benin Teaching Hospital Pharmacy, Benin City, Edo
The rats in the treatment groups (A, B, & C) received respectively,
0.25mg/kg, 0.70mg/kg and 1.43mg/kg body weight of sildenafil citrate
base dissolved in distilled water daily for 30 days, through orogastric
feeding tube, while that of the control group D, received equal volume
of distilled water daily during the period of the experiment. The rats
were sacrificed by cervical dislocation on day thirty-one of the
The skulls were opened using bone forceps to expose the brain of the
rat, and the lateral geniculate body was quickly dissected out and fixed
in10% formal saline for routine histological techniques.
The tissue was dehydrated in an ascending grade of alcohol (ethanol),
cleared in xylene and embedded in paraffin wax. Serial sections of 7
microns thick were obtained using a rotatory microtome. Some of the
deparaffinized sections were stained routinely with hematoxylin and
eosin (H&E) method.(31) The digital photomicrographs of the desired
sections were made in the Department of Anatomy research laboratory,
University of Benin, Nigeria for further observations.
Photomicrographs of the sections of
geniculate body (LGB) from the control group (D) showed normal
features, with the neurons appearing distinct and the glial cells normal
without vacuolation in the stroma (Figure 1). The sections of the
geniculate body (LGB) from the treatment (A, B, & C) groups showed
some varying degree of reduced cellular population, based on its sparse
distribution, degenerative changes, cellular hypertrophy, and
vacuolations appearing in the stroma. (Figure 2, 3 &4)
Fig.1: Control section of the
lateral geniculate body (Mag. x400)
Fig. 2: Photomicrograph of
treatment section of the
lateral geniculate body of rats that received 0.25mg/kg
of sildenafil citrate base dissolved in distilled water daily
for 30 days (Mag. X400)
Fig. 3: Photomicrograph of
treatment section of the lateral geniculate body of rats that received 0.70mg/kg of sildenafil
citrate base dissolved in distilled water daily for 30 days (Mag. X400)
Fig. 4: Photomicrograph of
treatment section of the lateral geniculate
body of rats that received 1.43mg/kg
of sildenafil citrate base dissolved in
distilled water daily for 30 days (Mag. X400).
The results (H & E) revealed
of sildenafil citrate showed some varied degree of cellular degenerative
changes, cellular hypertrophy, clustering of cells and intercellular
vacuolations appearing in the stroma of the treatment groups compared
to the control section of the lateral geniculate body of the adult
rat. Neuronal degeneration has been reported to result in cell death,
which is of two types, namely apoptotic and necrotic cell death. These
two types differ morphologically and biochemically.(32) Pathological
or accidental cell death is regarded as necrotic and could result from
extrinsic insults to the cell such as osmotic, thermal, toxic and
effects.(33) It was reported that cell death in response to neurotoxins might
trigger an apoptotic death pathway within brain cells.(34)
The process of
necrosis involves disruption of the membranes structural and functional
integrity. Cellular necrosis is not induced by stimuli intrinsic to
the cells as in programmed cell death (PCD), but by an abrupt
perturbation and departure from the normal physiological conditions.(35) There is the need to further investigate the actual mechanism
by which sildenafil citrate induced neuronal degeneration in the lateral
geniculate body of adult Wistar rat in this study.
Extensive cell death in the central nervous system is present in all neurodegenerative diseases.(34) The type of nerve cell loss and the
particular part of the brain affected dictate the symptoms associated
with an individual disease.(34) In this study sildenafil citrate may
have acted as toxin to the cells of the lateral geniculate body (LGB),
affecting their cellular integrity and causing defect in membrane
and cell volume homeostasis.
In cellular necrosis, the rate of progression depends on the severity
of the environmental insults. The principle holds true for toxicological
insult to the brain and other organs.(35) The prime candidates for
inducing the massive cell destruction observed in neurodegeneration
are neurotoxins.(34) The latter when present at a critical level can
be toxic to the brain cells they normally excite.(34) It is inferred
from this results that prolonged and high dose of sildenafil citrate
resulted in increased toxic effects on the LGB.
The vacuolations observed in the stroma of the lateral geniculate body
in this experiment may be due to sildenafil citrate interference. The
cellular hypertrophy observed in this experiment may be due to the
effects of sildenafil citrate on the lateral geniculate body. This study
may underlie the possible neurological symptoms such as dizziness and
tinnitus. Sildenafil citrate has been implicated as a possible cause
of blindness: diagnosed as nonarteritic anterior ischemic optic
study revealed that high doses and long term administration of
citrate caused some varied degree of cellular degenerative changes,
spares cellular population, cellular hypertrophy and vacuolations in
the lateral geniculate body of adult Wistar rats. These results may
probably affect the functions of the lateral geniculate body in visual
sensibility in adult Wistar rats.
recommended that further studies be carried out to examine these findings.
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