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Egypt. J. Histol. Vol. 33, No. 2, June, 2010: 213 - 223
A Histological Study on the Effect of Diclofenac Sodium (Declophen)Administration on Thyroid Follicular Cells of Albino Rats
Nadia M. El-Rouby
Histology Department, Faculty of Medicine, Cairo University
ABSTRACTIntroduction: Diclofenac Sodium (declophen) is a nonsteroidal anti-inammatory drug recently categorized as thyroidantagonist.
Aim of the Work: To determine the histo-physiological changes that might occur in the thyroid follicular cells afterdeclophen administration and evaluate their reversibility.
Materials and Methods: Thirty adult male albino rats were randomly divided into three groups; Group I (Control
group), Group II received declophen (8 mg/kg /day) for one week then sacriced. Group III received declophen asgroup II and then sacriced one week after drug withdrawal. Blood samples were collected to estimate T3, T
4and TSH.
Thyroid glands were processed for microscopic examination. Mean follicular diameter and mean height of thyrocytes
were morphometerically evaluated and statistically analyzed.
Results: Declophen signicantly decreased T3level which did not return back to normal in group III. Histologically,
group II showed considerable light microscopic changes as focal distension of follicles that were lined with attened
epithelium. Their colloid revealed minimal peripheral vacuolations. Some follicles showed shedded epithelial lining.
Others appeared irregular with disrupted epithelium. That epithelium had irregular dark pyknotic nuclei and vacuolated
cytoplasm. Some follicles had apparently little colloid. Ultrastructural changes included dilated rER with electron lucid
material and many darkly stained lysosomes. Group III showed some changes compared with Control. Statistically, mean
follicular diameter of group II increased signicantly while mean epithelial height decreased signicantly compared to
Control. Group III revealed neither signicant increase in mean follicular diameter or decrease in epithelial height in
comparison with the control.
Conclusion: Declophen has toxic effect on the thyroid follicular cells which was incompletely recovered. So it shouldbe discontinued prior to evaluation of thyroid functions.
Original Article
Key Words:Declophen, follicular cells, thyroid gland,rats.
Corresponding Author:Nadia M. El-RoubyTel.:0111675532 E-mail: [email protected]
(ISSN: 1110 - 0559)
20 (1185-2010)
INTRODUCTION
Many factors including drugs can inuence thyroid
function in experimental animals and humans. Studies
in humans reported signicant effects of non steroidal
anti-inammatory drugs (NSAIDs) on thyroid tests,
which can lead to misinterpretation of the result and
inappropriate therapeutic decision1-3.
The role of NSAIDs in causing thyroid dysfunction
is quite often forgotten. These drugs might inuence
thyroid hormone homeostasis at any level from their
synthesis, secretion, and transport or end-organ action
as it might interfere with thyroid hormone binding
sites (competitive inhibition). They might also alter
the synthesis and secretion of thyrotropin (Thyroid
Stimulating Hormone: TSH)4,5. Some cases, however,
showed clinically apparent thyroid disease6.
Diclofenac Sodium (Declophen) is a potent NSAID.It has anti-rheumatic, anti-inammatory, analgesic
and anti-pyretic actions. It is commonly used as a pain
killer in many cases including rheumatoid arthritis,
dysmenorrhea, artheralgia, tooth ache and postoperative
pain7. Sometimes the drug may be used in high dosesdue
to severe agonizing pain or by mistake.
As NSAIDs are used more and more frequently in
human, it is important to know to what extent they can
inuence the thyroid gland. Reviewing the literature
showed that the inuence of NSAIDs, including
declophen, on the concentration of thyroid hormones
hasbeen established. However, there have been very few
previous studies demonstrating the effect of declophen
on the histological architecture of thyroid gland8. So
the objective of the present study was to evaluate the
declophen-induced alterations in the histological structure
and function of the thyroid follicular cells. It was also
aimed to evaluate the reversibility of such changes.
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Nadia M. El-Rouby
MATERIALS AND METHODS
A- Drug:
The drug used was Diclofenac Sodium (declophen),
presented as ampoules of 75 mg/3ml (Pharco
Pharmaceutical, Alexandria, Egypt). The dose used for
rats was 8 mg/kg body weight9. The drug was given daily
for a week by intramuscular (I.M) route. The control rats
were given physiological saline I.M. in the same volume
daily.
B- Animals:
Thirty adult male albino rats were used in this study.
Theywere obtained from Kaser El -Aini animal house.
Their weights ranged between 150-200 g. They were
kept under good hygienic conditions, fed ad libitum and
allowed free water supply. Rats were divided randomlyinto three equal groups as follows:
Group I: (Control Group):
Rats were given physiological saline daily ina similar
manner to other groups. Five rats were sacriced with
animals of group II and the other ve rats were sacriced
with animals of group III.
Group II: (Experimental Group):
Rats were given declophen as an I.M. daily dose of 8mg/kg body weight 9 for one week. After that week, the
rats were sacriced.
Group III: (Recovery Group):
Rats received declophen as in group II. The rats were
kept alive for another week without treatment. On the
15th day of the beginning of the experiment these rats
were sacriced.
Methods:
At the end of the experimental period, the animalswere sacriced under ether anaesthesia. Blood samples,
from all animals, were collected for hormonal assay.
Then, the thyroid gland of each rat was excised.
Hormonal Assay:
Hormonal assay was carried out at the Clinical
Pathology Department, Faculty of Medicine, Cairo
University, to determine the serum levels of T3, T
4and
TSH.
Histological Study:
1. For Light Microscopy: The thyroid tissues
were xed in 10% formol saline and processed
for parafn blocks. Sections of 5 micrometer
thickness were cut and stained with hematoxylin
and eosin (H&E).
2. For Transmission Electron Microscopy (TEM):Thyroid tissues were rinsed in phosphate buffer
(PH 7.4) then xed in 2.5% gluteraldehyde, post
xed in 1% osmium tetroxide andembedded in
epoxy resin. Semithin sections of 1 micrometer
thickness were cut on an LKB ultramicrotome
and stained with toluidine blue. Ultrathin
sections were stained with uranyl acetate and
lead citrate10 to be examined under Joel EM
100 S TEM using an accelerated voltage of 60
KV.
Morphometric Analysis of Both Thyroid Follicular
Diameter and Follicular Epithelium Height:
Leica Qwin 500 Ltd, image analysis system was used
to determine the diameter and the follicular epithelium
height of thyroid follicles. The two parameters were
measured in micrometers using lowpower (X 100) and
high power (X 400) magnication, respectively. The
internalfollicular diameters of 50 follicles, in 10 random
elds, of the thyroid gland of each rat of the different
groups were measured. They were measured on diagonal
axes. The mean of these two readings was then taken
as the internal diameter of the follicle. To measure the
epithelial height, 50follicles from each rat in 10 randomelds were chosen. The epithelial height was measured
at two points on thesame axis of each follicle. The mean
of these two readings was then taken as the epithelial
height. The meanvalue and Standard Deviation (SD) of
the data obtained for each group were calculated.
Statistical Analysis:
Statistical analysis was performed on IBM/PC
using SPSS (Version 11) / PC program. Comparison of
signicance between the different groups was made using
student T test11. Results were considered signicant
when probability (p) 0.05.
RESULTS
During the experiment, three rats died; two from the
experimental group (Group II) and one from the recovery
group (Group III).
Hormonal Assay:
It was clear that T3 was signicantly decreased in
both the experimental and recovery groups (P< 0.05)
compared to the control. On the other hand, there wasno signicant change of both T
4 and TSH (P >0.05)
compared to the control (Table 1 and Chart 1).
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A Histological Study on the Effect of Diclofenac Sodium (Declophen) Administration on Thyroid Follicular Cells of Albino Rats
Table 1:The mean values of T3in g/dL, T
4in g/dL and TSH in U/mL SD in different groups:
Item Control group Experimental group Recovery group
T3: Mean SD
T test3.9685 .09540
2.7100 .07071
* P1< 0.05
3.0990 .02767
* P2< 0.05
T4: Mean SD
T test2.6270 .02830
2.6150 .02550
P1 >0.05
2.6000 .02944
P2 >0.05
TSH: Mean SD
T test0.0118 0.00301
0.0137 0.00295
P1 >0.05
0.0120 .00267
P2 >0.05
P1 = between the experimental group and control group.
P2= between the recovery group and control group.
* Signicant P value.
Histological Results:
Group I (Control Group): The thyroid gland ofcontrol rats was composed of follicles lined with a
single layer of cuboidal follicular cells, and lled with
acidophilic homogenous colloid having peripheral
vacuolations (Figs. 1-A and B). The thyroid follicles
were surrounded by vascular connective tissue stroma
(Figs. 1-A and 2-A).The follicular cells had vesicular
nuclei and prominent nucleoli (Fig. 2-A). Electron
microscopy revealed that the follicular cells hadeuchromatic nuclei, rough endoplasmic reticulum and
mitochondria. The apical cytoplasm revealed secretory
vesicles. The colloid showed peripheral vacuolations in
the form of electronlucid areas (Fig. 2-B).
Group II (Experimental group): Examinationof the thyroid gland of rats of the experimental group
revealed focal markedly distended thyroid follicles.
These follicles were lined mostlywith attened epithelial
cells that had attened nuclei. Their colloid showed
nearly absent peripheral vacuolations (Fig. 3-A). Some
follicles revealed shedded cells. The interstitial tissue haddilated blood vessels (Fig. 3-B). The thyroids of some
animals revealed focal involuted follicles with minimal
Chart 1:The mean value of T3, T
4& TSH levels.
was interrupted (Fig. 4-B). The lining follicular cellsof
the damaged follicles had darkly stained irregular and
pyknoticnuclei. The cytoplasm of the affected thyrocytes
was vacuolated (Figs. 5-A and B). The follicles showed
variable density of colloid staining. Mast cells werefrequently seen in the interstitial tissue close to blood
vessels (Fig. 6). Electron microscopy revealed that the
nuclei of the affected follicular cells appeared indented
and hetrochromatic with dilatation of the peri-nuclear
space. The cisternae of rER were dilated and contained
amorphous lightly stained material (Figs. 7 and 8).
The cytoplasm showed many darkly stained lysosomes
and prominent Golgi complex (Fig. 9). The distended
follicles were lined with attened thyrocytes that had at
nuclei (Fig. 10).
Group III (Recovery Group): The thyroid folliclesof rats of thisgroup started to regain their activity andnormal appearance but patchy in distribution. These
follicles were lined with cubical epithelium and showed
peripheral vacuolations of their colloid content. Many
distended follicles were still seen. These follicles
were lined with attened thyrocytes. Their colloid had
minimal peripheral vacuolations. Also, involuted and
distorted follicles persisted (Fig. 11). The follicular cells
had vesicularnuclei. Some mast cells with darkly stained
granules were seen in the surrounding connective tissue
beside the blood vessels (Fig.12). Electron microscopy
revealed that the follicular cells appeared more or less
normal compared with the control group. They hadmore or less regular euchromatic nuclei with prominent
nucleoli. The cytoplasm had more or less normal rER
cisternae but many vacuoles and many darkly stained
lysosomes were still seen in some follicular cells
(Figs. 13 and 14). Some follicular cells showed sings of
regeneration as they were binucleated (Fig. 15).
Morphometric Study and Statistical Analysis:
The mean diameter of thyroid follicles of rats of the
experimental group was signicantly increased (p1< 0.05)
compared to thecontrol group while the mean folliculardiameter of thyroid folliclesof the recovery group was
insignicantly increased (p 2 >0.05) incomparison with
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Nadia M. El-Rouby
Table 2: The mean follicular diameter in m SD of thyroid follicles of different animal groups:
Control group Experimental group Recovery group
Mean follicular diameter in m
T test35.79.6
51.913
* P1< 0.05
36.69.9
P2>0.05
P1 = between the experimental group and control group.
P2= between the recovery group and control group.
* Signicant P value.
Chart 2: The mean follicular diameter of thyroid follicles of the different groups.
The mean epithelial height of thyroid follicles of
the experimental group was signicantly decreased(p1< 0.05) compared to the control group while the mean
Table 3:The mean value of epithelial height of thyroid follicles in m SD in different groups:
Control group Experimental group Recovery group
Mean epithelial height in m
T test9.21.6
6.81.4
* P1< 0.05
8.91.9
P2>0.05
P1 = between the experimental group and control group.
P2= between the recovery group and control group.
* Signicant P value.
epithelial height of the recovery group was insignicantly
decreased ( p2 >0.05) compared with the control group(Table 3 and Chart 3).
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A Histological Study on the Effect of Diclofenac Sodium (Declophen) Administration on Thyroid Follicular Cells of Albino Rats
Fig. 1: Photomicrographs of sections in the thyroid gland of a control rat(group I) showing:
a. Normal thyroid follicles lined with simple cuboidal epithelium and
lled with colloid (C). Note blood vessels (BV) in the surrounding
connective tissue stroma. H&E X 200.
b. The colloid (C) has peripheral vacuolations (V). H & E X 400.
Fig. 2: Photomicrographs of:a. Semithin section in the thyroid gland of a control rat. It shows that
the follicles are of variable sizes and lined with cuboidal follicular
cells that have vesicular nuclei (N). The follicles are lled with
colloid (C). Note that the stroma has many blood capillaries.
Toluidine blue X 1000.
b. TEM section of a control rat thyroid showing a part of thyrocyte.
The colloid (C) shows two electron lucid areas (V) of peripheral
colloid vaculations. Cisternae of RER and mitochondria (m) are
scattered throughout the cytoplasm. Many secretory vesicles
(S) in the apical cytoplasm and part of the nucleus (N) are seen.
Orig mag X 2000.
Fig. 3: Photomicrographs of sections in the thyroid gland of rats from theexperimental group (Group II):
a. Reveals markedly distended thyroid follicles. They are lined mainly
by at cells with at nuclei (arrow) and few low cuboidal cells with
apparently rounded nuclei (arrow heads). The colloid (C) shows
apparently no peripheral vacuolations. H&E X 400.
b. Shows that some follicles have shedded epithelial lining (*). The
thyrocytes of most of the follicles have vacuolated cytoplasm
(arrow). Note the dilated blood vessel (b.v). H&E X 400.
Fig. 4: Photomicrographs of sections in the thyroid gland of rats from theexperimental group (Group II):
a. Shows thyroid follicles of variable activity as some follicles are
markedly distended (1) and other follicles appear involuted (2).
These follicles have minimal amount of colloid. H&E X 200.
b. Reveals a follicle with interrupted follicular wall (arrow). The
adjacent follicles showing thyrocytes with vacuolated cytoplasm
(curved arrow). H&E X 400.
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Nadia M. El-Rouby
Fig. 5: Photomicrographs of semithin sections in the thyroid gland of ratsfrom the experimental group (Group II):
a. Shows that the follicles have vacuolated colloid (C). The thyrocytes
have vacuolated cytoplasm (V) and indented darkly stained
pyknotic nuclei (arrow). Toluidine blue X 1000.
b. Shows that the destroyed follicles reveal shedded cells into
their lumina (encircled).The nuclei of the shedded cells appearirregular and darkly stained. The thyrocytes reveal vacuolated
cytoplasm (V). Toluidine blue X 1000.
Fig. 6: A Photomicrograph of semithin section in the thyroid gland of arat from the experimental group (group II). It shows a distorted follicle
with shedded cells (S) into its vacuolated colloid (C). These shedded cells
have irregular indented darkly stained nuclei. The colloid (C) reveals
variable density of staining. The thyrocytes show vacuolated cytoplasm
(V). The surrounding stroma is very vascular. Mast cell (M) is seen close
to interstitial blood vessel. Toluidine blue X 1000.
Fig. 7: A Photomicrograph of TEM section showing two thyrocytes oftwo adjacent follicles of a rat from the experimental group, the upper
left thyrocyte is of a damaged follicle showing dilated rER (d rER). Itsnucleus is hetrochromatic and indented (arrows). The lower thyrocyte is
related to more or less normal follicle with normal cisternae of rER but
with apparently more darkly stained lysosome (L) Note the projecting
Fig. 8: A Photomicrograph of TEM section showing two thyrocytesof a thyroid follicle of a rat from the experimental group. It shows
dilated cisternae of rER (d rER) with amorphous material (*). The
nuclei (N) appear indented with dilated peri-nuclear space (arrows).
The nuclei have prominent nucleoli (Nu) and hetrochromatin (h).
Original mag X 6000.
Fig. 9: A Photomicrograph of TEM section of a thyrocyte from a ratof the experimental group reveals apical microvilli (Mv) projecting into
the lumen that has colloid (C). Many darkly stained lysosomes (L) are
seen. The cytoplasm shows prominent Golgi complex (G) and cisternae
of rER. Original mag X 8000.
Fig. 10: A Photomicrograph of TEM section of the thyroid gland from arat of the experimental group (group II). It shows two follicular cells withattened nuclei. The nuclei have hetrochromatin. The cytoplasm shows
darkly stained lysosomes (L). The colloid (C) is apparently homogenous.
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A Histological Study on the Effect of Diclofenac Sodium (Declophen) Administration on Thyroid Follicular Cells of Albino Rats
Fig. 11:A photomicrograph of thyroid gland of a rat from the recoverygroup (Group III). It reveals some recovered follicles. These follicles
show vacuolated colloid (V). Other follicles appear distended with
colloid (C) and lined with at epithelial cells. Note that there are still
some distorted follicles (D). A forth group of involuted (I) follicles areseen. H&E X 200.
Fig. 12: A photomicrograph of semithin section in the thyroid gland ofa rat from the recovery group (Group III). It shows that the follicles are
lled with homogenous colloid (C) and lined with cuboidal cells that
have vesicular rounded nuclei (curved arrows) and some low cubical
cells with attened nuclei (straight arrows). Some mast cells (m) are seen
in the stroma. Toluidine blue X 1000.
Fig. 13:A photomicrograph of TEM section of the thyroid gland of a
rat from the recovery group (group III). It shows a follicular cell withmore or less euchromatic nucleus (N) and prominent nucleolus (nu). The
cytoplasm reveals more or less normal cisternae of rER, many vacuoles
(V) and some electron dense lysosomes (L) The lumen shows colloid (C)
Fig. 14: A photomicrograph of TEM section of the thyroid glandfrom a rat of the recovery group (Group III) showing two thyrocytes
with more or less normal rER. Their nuclei appear euchromatic but
with some irregularity. The cytoplasm reveals many vacuoles (V) and
mitochondria (M). Many electron dense lysosomes (L) are observed.Original mag X 6000.
Fig. 15:A photomicrograph of TEM section of a thyrocyte from a ratof the recovery group (Group III) showing two nuclei with prominent
nucleoli. The cytoplasm shows vacuoles (V) and electron dense
lysosomes (L). Original mag X 6000.
DISCUSSION
There is a list of medications that alter thyroid
function tests. This list include furosemide, NSAIDs
(salicylate, diclofenac sodium), heparin, amiodarone andiodinated contrast media12. As NSAIDs are commonly
used drugs so thyroid dysfunction is a potentially
forgotten complication of NSAIDs therapy5.
In the current study, declophen was administered to
rats of group II daily for one week to evaluate its effect
on the structure and function of the thyroid gland. Group
III received declophen for the same duration as group II
and this was followed by another week without treatment
for recovery to asses the reversibility of these changes.
Death of rats that occurred during the experiment was
most probably due to liver and/or kidney affection9,13
.
The present study reinforced the previous recorded
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Nadia M. El-Rouby
including diclofenac sodiumcould lower serum T3while
T4 and TSH were not affected. This might be because
NSAIDs block peripheral (tissue) conversion of T4 to
T3and produce a low concentration of T
3as most of T
3
is produced from peripheral conversion of T4 to T
3by
enzyme 5- deiodinase. The levels of T4and TSH were not
affected. This was most probably because T4is strongly
bound to plasma proteins and its biological half life is
long(6-7 days) so subsequently TSH remained without
change17. Another cause for insignicant change in T4
level could be because the thyroid gland is a unique
gland that stores its hormones extracellular in an amount
sufcient for weeks18. NSAIDs including declophen
affected the tests of the thyroid gland through alteration
in the synthesis, transport, and metabolism of thyroid
hormones1,3,5,16. This was proved by both light and
electron microscopic ndings. At the light microscopic
level; some follicles showed degenerative changes in the
form of shedded degenerated thyrocytes. The thyrocytesof more affected follicles had vacuolated cytoplasm and
small, irregular dark pyknotic nuclei. At the level of TEM;
the nuclei of thyrocytes were indented, heterochromatic
with widening of the peri-nuclear space. This might be
attributed to its connection to dilated cisternae of rER. The
rER cisternae were dilated and had intra-luminal electron
lucid material of storedunprocessed protein. Also there
was apparent increase in dark stainedlysosomes.
Light microscopic examination of thyroid glands
of rats of the experimental group (Group II) revealed
marked distortion of follicularstructure. Some folliclesappeared distended and lined by at follicular cells
due to increased their colloid content that had minimal
peripheral vacuolations denoting hypoactivity of these
follicles. Other follicles appeared small in size with
apparently little colloid. These follicles mightbe newly
formed, collapsed or involuted follicles. A third groupof
follicles had shedded epithelial cells. These changes could
be attributed to cellular distension with accumulated
colloid which resulted in cellular disruption and collapse
with subsequent collapse of the follicles. The degenerated
cells had dark stained nuclei and vacuolated cytoplasm.
These ndings were recorded in cases of thyroiditis19.
Many mast cells were observed frequently in the inter-follicular connective tissue beside blood vessels. This
nding might be due to an allergic reaction occurred in
the thyroid gland as these mast cells secrete cytokines
and chemical mediators responsible for allergic reaction.
This allergic reaction might be because NSAIDs altered
plasma proteins. These NSAIDs- altered proteins could
become antigenic. By time these antigens would become
immunogens20. Former studies reported that mast cells
participate in the process of thyroid hormone secretion
and in thyroid gland activity. Mast cells might mediate
the action of TSH on follicular cells. TSH has been
shown to promote the release of serotonin from thyroidmast cells. Serotonin activates thyroid follicular cells
by enhancing them to extend pseudopodia and engulf
Some follicles revealed variable staining density of
colloid. This might indicatevariable follicular activities.
This nding was supported by Wollman et al.23 who
mentioned that density of staining of the accumulated
colloid varied from follicle to follicle and correlated the
staining reaction of the colloid with the activity of the
follicle. Other follicles had vacuolated colloid which
might be due to defect in pinocytosis of follicular cell.
Thyrocytes of the more affected follicles revealed
pyknotic nuclei and vacuolated cytoplasm. This could
explain the lowered level of thyroid hormone (T3)14.
Ultrastructurally, the follicular cells of the damaged
follicles revealed widening of the peri-nuclear space,
irregularity and indentationof the nuclei with chromatin
condensation, dilatation of rER withintra-luminal electron
lucid material, apparently increased darkly stained
lysosomes and prominent Golgi complex. Widening of
the peri-nuclear spacemight be due to shrinkage of thenuclei due tothe toxic effect of declophen. Also, this might
be attributed to its connection to dilated cisternae of rER.
The pyknosisof the nuclei and condensation of chromatin
observed in thyrocytes of declophen treated rats have been
also observed in other tissues as rat liver cells exposed
to NSAIDs24. These changes could be degenerative
changes. Declophen might induce these degenerative
changes either directly or indirectly. This nding was
in agreement with Boelsterli25and Moorthy et al.26who
observed that declophen caused injury of liver cells and
they referred this to immune mediated response. Many
darkly stained lysosomes were seen in the cytoplasm ofthyrocytes of rats administered declophen. The apparent
increased number of lysosomes could be explained by
the accumulation of highly iodinated thyroglobulin that
was resistant to proteolysis27. Marked dilatation of rER
was an evidence of disturbed protein synthesis. This
dilatation could be due to retention of aberrant protein
within their cisternae. Therefore, this mightbe a form of
rER storage disease. This protein could not be processed,
folded and transported to appropriate sites. Disruption in
protein production might prevent synthesis of apoptosis
inhibitors and/or loss of essential proteins involved in
cellular homeostasis leading to cellular degeneration28,29.
The dilated rER might bethe cause of nuclear indentationand irregularity as the dilatedrER compressed the nucleus
causing its indentation and irregularity.
Using light microscopy, the thyroid gland of the
recovery group revealed that the gland needed more
time to return back to normal structure. The thyroid
follicles revealed patchy recovery. Some follicles were
still large in diameter and distended with colloid with
minimal peripheral vacuolations which indicated hypo-
activity. Other follicles were smaller in diameter, lined
with cuboidal cells mainly and their colloid had some
peripheral vacuolations i.e. these follicles regain theiractivity.
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A Histological Study on the Effect of Diclofenac Sodium (Declophen) Administration on Thyroid Follicular Cells of Albino Rats
appeared more or less normal with slightly indented
euchromatic nuclei and prominent nucleoli. The
cytoplasmic organelles were more or less normal in
appearance except for the presence of apparently more
darkly stained lysosomes. Some thyrocytes revealed
variable sized vacuoles in their cytoplasm. This indicated
that rat thyroid needed more time to recover completely.
Morphometeric study of thyroid follicles of rats of
theexperimental group (Group II) revealed statistically
signicant increase in the mean follicular diameter
and statistically signicant decrease in the mean
epithelial height in comparison with the control group
(Group I) which denoted hypoactivity of the gland.
This was proved histologicaly as many follicles were
markedly distended with colloid and linedmainly with
at cells. The colloid was homogenous acidophilic and
showed minimal peripheral vacuolations. The less active
follicles of the thyroid gland were distended by storedcolloid and the lining cells appear attened against the
follicular basement membrane17,30.
One week after declophen withdrawal (recovery
group; group III), the morphometeric analysis of the
thyroid follicles showed insignicant increase in the
mean follicular diameter of thyroid follicles and also
insignicant decrease in the epithelial height of the lining
follicular cellsin comparison to the control group. This
could be attributed to starting reactivity of the thyroid
gland as a result of recovery from the toxic effect of
declophen and elimination of harmful waste productsfrom the body.
CONCLUSION
Declophen, a cytotoxic drug, induced variable
structural and functional alterations in the thyroid
follicular cells of adult male albino rats. These alterations
were incompletely recovered. So, it is advisable to avoid
using declophen as rst pain killer and if it is used, thyroid
function tests results should be interpreted cautiously
in patients on declophen therapy. The drug should be
discontinued prior to evaluation of thyroid function.
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