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Indian Journal of Basic and Applied Medical Research; June 2015: Vol.-4, Issue- 3, P. 431-434
431
www.ijbamr.com P ISSN: 2250-284X , E ISSN : 2250-2858
Original article
Optical microscopic analysis of liver of sildenafil citrate treated albino
rats
Dr. K.V.P. Suriyakumari, Dr. Udayakumar R., Dr. Anurag Sood
Name of the Institute/college: Department of Anatomy, Sri Manakula Vinayagar Medical College and Hospital,
Kalitheerthalkuppam, Madagadipet, Pondicherry- 605107
Corresponding author : Dr. K.V.P. Suriyakumari
Abstract
Background: Sildenafil citrate, an oral therapy for Erectile dysfunction (ED), is a selective inhibitor of cGMP - specific
phosphodiesterase type 5 (PDE5). Our aim was to study the drug induced histological changes in the liver of Albino rats
treated with Sildenafil citrate.
Materials and methods: 48 healthy male Wistar Albino rats were chosen and divided into eight groups, each consisting of six
animals in it. Group S1 served as the control and was treated with conductivity water (@ 1µg /g body wt.)µ. Groups S2, S3,
S4 and S5 served as the experimental groups, being treated with a single dosage of the experimental drug (i.e.) Sildenafil
citrate (@ 1µg /g body weight) and were sacrificed after 1hr, 2 ½ hrs, 4 hrs, and 24 hrs. Groups S6, S7 and S8 were treated
with a single dosage of the drug for 15, 30 and 45 days and were sacrificed after 4hours of the last dosage. A vertical ventral
midline incision was made in the abdominal wall to collect the liver samples.
Result: Liver damaging effects were observed, more in the case of animals with prolonged exposure to Sildenafil citrate.
Conclusion: Sildenafil citrate, if administered to Albino rats on long- term basis, will have adverse effects on the structure
and vital metabolic functions of the Liver.
Introduction:
Erectile dysfunction (ED) is a common and
multifactorial disease that strongly impairs the
quality of life in many. 1, 2
It provides a paradoxical
situation to both the patients and physicians.
Approximately about 52% of the surveyed men
aged between 40 and 70 years suffer from some
degree of ED. 3 Though Sildenafil citrate, a
selective inhibitor of cGMP- Specific
Phosphodiesterase type 5 (PDE5), has been
reported to induce some mild side effects, is an
effective oral therapy for ED. 5, 6
The mode of
action of the drug has been elaborately studied by
various researchers. 5, 7, 8
Since Sildenafil citrate has
been the drug of choice even among common man,
it is worth studying the detrimental impacts on the
structure and functions of Liver of Albino rats. Our
aim was to study the long- term effects of
Sildenafil citrate on Liver of Albino rats
Materials and methods:
Sildenafil citrate (CAVERTA from India)
purchased from the market has been used as the
drug to carry out the present investigation. The
experimental animals were administered with the
above drug at the rate of 1µg/ g body wt. of the
animal, using conductivity water as the solvent.
48 healthy male Wistar Albino rats, weighing about
250- 300 gm, were obtained from Animal House,
Raja Muthiah Medical College, Annamalai
University, Tamil Nadu. The experimental protocol
was approved by the Institutional Animal Ethical
Committee following the guidelines of CPCSEA
(Committee for the purpose of Control and
Indian Journal of Basic and Applied Medical Research; June 2015: Vol.-4, Issue- 3, P. 431-434
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Supervision of Experiments on Animals for
Laboratory Animal Facility).
The animals were acclimatized for a period of
seven days before starting the study. Standard
environmental conditions such as temperature (24±
2°C), humidity (60- 70%) and 12 hours of light/
dark cycle was monitored. Food and water were
allowed ad libitum under strict hygienic conditions.
For the present study, the chosen animals have
been divided into eight groups, each consisting of
six animals in it. Here S1 served as the control
while the rest of the seven groups, namely S2, S3,
S4, S5, S6, S7 and S8 served as the experimental
ones. The control animals were treated with a
single dosage of conductivity water while the
experimental groups S2, S3, S4 and S5 were treated
with a single dosage of the drug and sacrificed after
1 hr, 2 ½ hrs, 4 hrs and 24 hrs of the last dosage.
The experimental animals belonging to the groups
S6, S7 and S8 were treated with a single dosage of
the drug daily for 15, 30 and 45 days respectively
and sacrificed after 4 hours of the last dosage.
Chloroform anaesthesia was used and a vertical
ventral midline incision was made in the abdominal
wall to collect the liver samples. The organs were
preserved in 10% formalin, processed and stained
with Eosin and Hematoxylin stain.
Result:
The outcome of the present investigation clearly
points out the following observations:
The section of Liver of Control (S1) animals
indicates the normal architecture of Liver of Albino
rats [Figure 1]. However, in the case of S2 (1 hr), S3
(2 ½ hrs) and S4 (4 hrs) groups; there occurred a
mild congestion of the central vein and dilation of
the hepatic artery in the portal triad. The section of
Liver of S4 (4 hrs) group of animals, shows clearly
the increased dilation of hepatic artery
accompanied by the increased congestion of the
central vein. As the animals tried to regain the
normal conditions, the Liver samples of S5 (24 hrs)
group, indicate the normal pattern of Hepatic lobule
and central vein.
The Liver samples of S6 (15 days) and S7 (30 days)
group of animals quite obviously exhibits marked
dilation of the sinusoidal spaces and congestion
ofcentral vein besides the occurrence of crenated
nucleus and vacuolated cells [Figure 2 and Figure
3].
In the case of S8 (45 days) sample the histo-
architecture of the hepatic lobule has been found to
be disturbed prominently. Besides the congestion
of the central vein and the disappearance of the
Hepatic cells, there occurred an increased number
of vacuolated cells as well as necrotic cells [Figure
4].
Discussion:
Long- term Caverta treatment of Albino rats leads
to well marked changes in Liver such as distorted
histo- architecture of the Hepatic lobule, most
prominent central vein congestion, widened
sinusoidal spaces, disappearance of Hepatic cells
towards the central vein, increased number of
vacuolated cells and necrotic cells. Similar
symptoms were observed in the case of Chickens
fed with Giberellic acid, 9 Albino rats treated with
Gibberellin A3, 10
Albino mice administered with
chemicals such as Zineb and Maenab 11 and mouse
treated with brodifacum. 12
Occurrence of vacuolated cells is one of the
important primary responses to all forms of cell
injury. Increase in the number of vacuolated cells
due to the long- term drug exposure, may be
attributed to the increases permeability of cell
membrane leading to an increase of intracellular
water ultimately resulting in cytoplasmic
vacuolization. As Liver is responsible for
detoxification and excretion of xenobiotics, it is the
first organ to be exposed to drug hazards via portal
circulation. Therefore, the cell infiltration and the
Indian Journal of Basic and Applied Medical Research; June 2015: Vol.-4, Issue- 3, P. 431-434
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increased number of necrotic cells in the Liver may
cause a decrease in the detoxification capacity of
Liver. 13
Conclusion:
It is quite obvious, from the present study that
Sildenafil citrate (CAVERTA), if administered for
a long- term, will produce adverse effect on the
structure and vital functions of Liver of Albino rats.
Figure1: Section of Liver of Albino rats [0 hr]
showing (1) Hepatocytes, (2) Normal Sinusoidal
space and (3) Portal triad
Figure 2: Section of Liver of drug- treated Albino
rats [15 days] showing (1) Marked dilation and
congestion of Sinusoidal Space, (2) Normal
Hepatocytes and (3) Vacuolated Hepatocytes
Figure 3: Section of Liver of drug- treated Albino rats [30 days] showing (1) Vacuolated cells and (2)
prominent dilation and congestion of sinusoidal
space
Figure 4: Section of Liver of drug- treated Albino
rats [45 days] showing (1) Vacuolated cells and (2)
Necrotic cells
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