optical microscopic analysis of liver of sildenafil

Indian Journal of Basic and Applied Medical Research; June 2015: Vol.-4, Issue- 3, P. 431-434

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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


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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


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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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optical microscopic analysis of liver of sildenafil

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