EFFECT OF CHRONIC EXPOSURE OF CADMIUM CHLORIDE IN DRINKING  WATER ON STRUCTURAL AND FUNCTIONAL ASPECTS OF THYROID GLANDIN MATU


Iraqi J Pharm Sci, Vol.19 (1) 2010                                 Effect of cadmium chloride in thyroid gland 

 

69 

 

Effect of Chronic Exposure of Cadmium Chloride in Drinking Water 

on Structural and Functional Aspects of Thyroid Gland in Mature 

Male Rabbits
#
  

 

Samir  H. Cheyad*
,1

   ,   Kalisa K. Khudier**  and     Khtan A. AL-Mzain** 

 
* Ministry of Industry ,General Commission for Industrial Research  and  Development AL-Razi Center   

    for Research and Medical Diagnostics.  

           ** Department of Physiology , College of Veterinary Medicine ,University of Baghdad , Baghdad, Iraq. 

 

 

Abstract 
         The effect of chronic exposure to two different levels of cadmium chloride (CdCl2) 30 ppb and 

40 ppb in drinking water for 12 weeks on thyroid function of mature male rabbits was studied. 

Eighteen mature male rabbits  were randomly divided into three groups (each of six ) , control group 

(group I ): were offered ordinary tap water , and treated groups (II and III ) were offered tap water 

containing 30ppb and 40 ppb respectively for 12 weeks .Serum concentration of  thyroxin (T4 ) and 

triiodothyronine (T3) were measured every six weeks ,as an index  of  thyroid function , further more ,  

section of thyroid gland were prepared for histological studies. The results showed that  chronic 

exposure of male rabbits to two  different levels of  CdCl2  caused significant decrease (p<0.05) in 

serum T3 and T4 in both treated groups in compared with control group, in addition, there were 

histological changes in thyroid gland of treated groups manifested by hyperplasia with presence of 

large number of varying size of microfollicels and hypertrophic thyrocytes, small colloid with little 

secretion .  

Key wards: Cadmium, Thyroid gland, Thyroxin, Triiodothyronin, Thyrocyt 

 الخالصة
ى ( فً هاء جضء تالثلٍْ  03،  03اجشٌد ُزٍ الذساسح لوعشفح ذأثٍش الرعشض الوضهي لوسرٌٍْي هخرلفٍي هي كلْسٌذ الكادهٍْم )          

اسًثا تالغا قسود عشْائٍا الى ثالز  21ذن اسرخذام  3اسثْع على ّظٍفح الغذج الذسقٍح فً ركْس االساًة الثالغح  21الششب ّلوذج 

(  II group( اسرلود هاء عادي طٍلح فرشج الرجشتح ّهجوْعرً الوعالجح )     group Iهجاهٍع  هرساٌّح :  هجوْعح السٍطشج )

( اسرلود هاء الششب هضافا الٍَ  III group، جضء تالثالٍْى ( ّ ) 03ششب الوضاف الٍَ كلْسٌذ الكادهٍْم ترشكٍض )اسرلود هاء ال

ّذشاي اٌْدّ      T4اسثْعا ذن قٍاط ُشهًًْ الغذج الذسقٍح الثاٌشّكسٍي  21جضء تالثلٍْى ّلوذج  03كلْسٌذ الكادهٍْم ترشكٍض 

اخز الوقاطع الٌسٍجٍح للغذج الذسقٍح. اظِشخ الٌرائج اى ذعشض ركْس االساًة الوضهي كل سد اساتٍع فضال عي   T3ثاٌشًٍّي  

ً فً هصل الذم ف    T3  ّT4فً ذشكٍض ُشهًًْ   لوسرٌٍْي هخرلفٍي هي كلْسٌذ الكادهٍْم فً هاء الششب قذ سثة اًخفاضا هعٌٌْا

                     سٍجٍح للغذج الذسقٍح حذّز حالح فشط الٌسٍجهقاسًح هع هجوْعح السٍطشج كوا اظِشخ الفحْصاخ الٌهجاهٍع الوعالجح 

 (hyperplasi ٍذوثلد تْجْد عذد كثٍش هي الخالٌا الذسقٍح ّتاحجام هخرلفح هحاطح تطثقح هي الخالٌا الطالئ )ح ) ــــhypertrophic 

thyrocyte   ( فضال عي ّجْد ًقص ّاضح فً كوٍح الغشّاى )colloid  ٌة هع قلح فً افشاصاذَ( داخل الجش . 

 

Introduction 
         Cadmium is modern toxic metals 

(discovered in 1817) . Its main use in 

electroplating because of its anticorrosive 

properties, it also used as color pigment of 

paints, plastics and as cathode material for 

nickel –cadmium batteries, cadmium is an 

important source of environment pollution 
(1)

. 

Hazardous waste disposal  sites are large 

source of Cd concentration found in soil and 

water .  Tobacco smoke is the main reason for 

cadmium accumulation in our body 
(2)

,on other 

hand , the major route of cadmium intake ( for 

non smoker ) is ingestion , this is largely  due 

to the presence of Cd ( 2-40 ppb )  in food staff 

of natural origin e.g. cereals beans , carrots , 

beverage, coffee and tea 
(3)

 ,or by the ingestion 

of contaminated food  especially fish  
(4, 5)

 . 

The acute toxic effect of Cd are generally 

restricted to the lung ,where as the effects 

following chronic Cd exposure in human are 

multisystemic and include nephropathies  

emphysematous alteration in the lung , 

cardiovascular disease , and bone damage 

possibly ( osteomalacia and osteoperosis ) 
(6)

 . 

Wealth of evidence suggested that heavy 

metals including cadmium exert profound 

toxic effects on the activities of a number of 

endocrine gland including thyroid gland 
(7,8)

 .  

 
# 
Based on oral presentation in the seventh scientific conference of the College of Pharmacy /University 

of Baghdad held in 26-27 November 2008. 

1Corresponding author E- mail : samir-cheyad@yahoo.com   
Received :14/4/2009  

Accepted : 9/5/2010

mailto:samir-cheyad@yahoo.com


Iraqi J Pharm Sci, Vol.19 (1) 2010                                 Effect of cadmium chloride in thyroid gland 

 

70 

 

Cadmium intoxication has been reported to 

reduce the thyroidal iodide uptake 
(7)

 and 

inhibits hepatic conversion of thyroxin (T4) to 

triiodothyronine (T3) in rats 
(9)

 and mice 
(10)

. It 

has been previously reported  that 

subcutaneous injection of cadmium chloride 

(CdCl2 ) (mg/kg B.W ) for ten weeks to male 

rabbits resulted in a significant reduction in 

serum T3 concentration and hepatic T4 

production 
(11)

 . The direct relationship 

between heavy metals  poisoning and thyroid 

dysfunction were studied in male rabbits by 

Ghosh and Battacharya ,1992 , within 24 hours 

of intramascular injection of CdCl2 (15mg/kg 

B.W) a significant increase in thyroid activity 

over the control with a concomitant rise in T3 

titer were observed .. The toxic effect of 

cadmium on thyroid gland functions has been 

studied , yet its effect at above the permissible 

level and below the toxic one are questioned , 

to this aim the present study dedicated .     

     

Materials and Methods 
         Number of mature male rabbits 800- 

1000 g of local breed were acclimated to 

holding  facilities for one week prior to 

commencement of dosing . Animals in all 

stages of experiment were housed in clear 

plastic cages in conditioned room (22-25 c◦ )  

with controlled lightening ,eighteen  rabbits 

were randomly and equally  divided into three 

groups and were treated for three months as 

fallow : group I, rabbits in this group were 

received tap water and served as a control 

group , the group II were received 30 ppb 

cadmium chloride  in drinking water , while 

the animals of group III were received 40 ppb 

of cadmium chloride in drinking water . 

Fasting blood samples were collected at zero, 

6, and 12
th

 weeks of experiment via cardiac 

puncture technique , then serum was separated  

and frozen at – 20 c◦ for hormonal analysis 

,tetraiodothyroninT4 and triiodothyronin T3 

were determined by using immuno assay 

detection
 (12)

. For histological studies rabbits 

were killed and a portion of trachea with intact 

thyroid gland was dissected free of connective 

tissue and preserved in 10% formaline buffer 

solution till the preparation of histological 

sections . Tissues were embedded in paraffin 

and several tissues sections were prepared, and 

stained with Hematoxylin- Eosin stain 
(13)

.Statistical analysis of data was done on the 

basis of two – way analysis of variance 

(ANOVA) , using a significant level of p < 

0.05  
(14)

 .       

Results 
         The effect of the two different levels of 

cadmium chloride on mean values of serum T3 

concentration of male rabbits are shown in 

table (1) , serum T3 concentration showed a 

significant decrease (p< 0.05 ) at the 6
th

 week 

of exposure to cadmium chloride   in group III 

and at the 12
th

  week of experiment in group II  

as compared with control . In cadmium treated 

groups , In table(2) thyroxin serum 

concentration significantly decreased (p<0.05) 

compared to control , such decrement was 

observed at the 6
th

 –12
th

 week of experiment. 

Within groups , the values tended to decrease 

significantly (p<0.05 ) with time (at 6
th

-12
th

 

week ) as compared with the pretreated  period 

. The histological structure of thyroid gland of 

un treated rabbits was shown in figure (1) , the 

thyroid follicles containing colloid of uniform 

color , oval in shape , lined by cuboidal 

thyroidal follicular cells , figures 2,3 illustrated 

the histological changes in thyroid gland of 

rabbits following 30 and 40 ppb of CdCl2 ( 

group II and group III ),the figures showed a 

case of hyperplasia manifested by presence of 

thyroid microfollicels of varying size lined by 

high columnar thyroidal follicular cells 

(hypertrophic thyrocyte ) ,   small colloid with 

little secretion in follicular lumen ( figure 2) , 

while the figure 3 showed a large area of 

irregular and varying size microfollicels with 

hypertrophic thyrocyte with little colloid 

secretion . 

Table 1 : Serum  triiodothyronine (T3) 

concentration  (nmol/l)  in  rabbits treated  

with two different levels of cadmium 

chloride  in drinking water.  

 

Groups 

Time 

( weeks) 

 

I 

 

II 

 

III 

Pre-

treatment 
0 

0.43± 0.01 

A          a 

0.44±0.56 

A           a 

0.44±0.01 

A          a 

D
u

r
in

g
 

tr
e
a

tm
e
n

t 
 

6 
0.45±0.01 

A           a 

0.43±0.01 

A          a 

0.41±0.02 

B         b 

12 
0.44±0.01 

A           a 

0.40±0.02 

B           b 

 

0.40±0.02 

B          b 

 

Values are expressed as mean ±SE n = 6/group 

Groups: I = control,  

II = rabbits received 30 ppb of cadmium 

chloride in drinking water,  

III = rabbits received 40 ppb of cadmium    

chloride in drinking water. 

Capital letters denote between group 

differences, P< 0.05 vs. control. 

Small letters denote within same group 

differences, P<0.05 vs. pretreated values. 

 

 

 

 



Iraqi J Pharm Sci, Vol.19 (1) 2010                                 Effect of cadmium chloride in thyroid gland 

 

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Table 2: Serum tetraiodothyronine ( T4)  

concentration (nmol/l) in rabbits treated 

with two different levels of cadmium 

chloride in drinking water.  
   

Groups 

Time 

( weeks) 

 

I 

 

II 

 

III 

 

Pre- 

treatment 

0 
58.17±0.7 

A         a 

57.42±0.56 

A         a 

57.12±0.42 

A           a 

D
u

r
in

g
 

tr
e
a

tm
e
n

t 6 
58.5±1.25 

A          a 

51.0±2.4 

B          b 

49.2±1.6 

B           b 

12 
58.35±1.3 

A         a 

44.5±1.9 

B         c 

41.7±0.4 

B         c 

Values are expressed as mean ± SE    n = 6/ group 

Groups: I = control,  

II = rabbits received 30 ppb of of cadmium 

chloride in drinking water,  

III = rabbits received 40 ppb of cadmium  

chloride   in   drinking water. 

Capital letters denote between group differences, 

P< 0.05vs. control. 

Small letters denote within group differences, 

 P< 0.05 vs. pretreated values. 

 

Figure 1:.Section in thyroid gland of 

untreated rabbit (group I), note thyroid 

follicles with thin epithelial lining cells 

(thyrocyte) (arrow), filled within colloid 

secretion (c). H&E, 40x 

 
 
 
 
 
 
 
 
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 2: Section in thyroid gland from 

cadmium treated rabbit (group II), note 

follicular- cells of varying size, high 

hypertrophic thyrocytes (arrow), with a little 

area of micro colloid secretion.(C ) H &E. 40x 

 

 
 
 
 
 
 
 
 
 
 
 
 

Figure 3 :Section in thyroid gland from 

cadmium treated rabbit (group III), showing 

large area of microfollicels of varying size with 

hypertrophic thyrocyte (arrow), and hardly 

little secretion in the lumen. (C) H&E. 40x  

 
Discussion 
         This study showed that exposure of 

rabbits to cadmium bring the animal to the 

case of hypothyroidism manifested by 

significant decrease in serum T3 and T4 

concentration associated with biological 

changes . To the best of our  knowledge , the 

effects of chronic exposure to CdCl2 at level 

30 and 40 times above the permissive level  on 

thyroid gland feature , has not been studied yet 

, however considerable body of evidence how 

exist attesting the involvement at heavy metals 

including cadmium in the toxicity of a number 

of endocrine glands including thyroid gland 
(8,9)

 . Many studies suggested the mechanisms 

including  affecting hepatic thyroxin 

metabolism through reduction in the activity of 

hepatic “ Outer Ring Deiodinase ORD” an 

C 



Iraqi J Pharm Sci, Vol.19 (1) 2010                                 Effect of cadmium chloride in thyroid gland 

 

72 

 

enzyme which responsible for conversion of 

major circulating form of thyroid hormone 

(T4) to more biologically active form(T3) with 

disruption of T3 signaling leading to reduction 

in T4 conversion 
(15)

. In addition cadmium may 

cause reduction of thyroidal I uptake by 

damages the structure and function of both 

follicular and parafollicular  cells of thyroid  
(9,10)

. Long term exposure to cadmium may 

induce the activity of hepatic microsomal 

enzyme especially UDP-GT (Uridine 

DiPhosphate Glucournyl Tranferase ) 
(16)

 and 

phenol sulftransferase 
(17)

 resulting in rapid 

clearance of T3 and T4 , on other hand , 

accumulation of cadmium in mitochondria of 

thyroid follicular epithelial cells might disturb 

the oxidative phosphorylation of this organelle 

with subsequent loss of energy supply leading 

to inhibition in the synthesis and release of 

thyroid hormone 
(18)

 . The suspected  selenium 

deficiency caused by cadmium treatment may 

lead to histological changes by activation 

fibrotic process in which inflammatory 

reaction and excess transforming growth factor 

B play a role in thyroid gland morphology . 
(19)

 

Gupta P and Kar A (1999) study the relation 

between cadmium and selenium , vitamin E 

and thyroid dysfunction in chicken, in this 

study they suggested that cadmium decrease 

T3, probably by inhibiting hepatic 5-

monodeiodinase (5D-I)activity, which is a 

selenium dependent function. Cadmium is 

known selenium antagonist while vitamin E 

facilitate selenium metabolism .Vitamin E was 

shown to protect against cadmium toxicity and 

maintain 5D-I activity and T3 levels, while the 

experimenters concluded that the metal –

induced inhibition in hepatic 5 D-I  activity is 

mediated through lipid piroxidation my 

conclusion is that the cadmium inhibited 5D-I  

activity by decreasing selenium.While vitamin 

E does decrease lipid peroxidation it does this 

by facilitating selenium metabolism and 

selenium is  the key metal in glutathione 

peroxidase which is a potent inhibitor of lipid 

peroxidation 
(9)   

Accordingly we can speculate 

that selenium deficiency may occur in this 

study following cadmium exposure resulting in 

the damage of thyroid gland , decrease the 

concentration of both (T3 and T4) and inhibit  

monodeiodinase activity leading to state of 

hypothyroidism .  

 

Acknowledgment 
        The  author  is  grateful to Dr.Barrh N. 

Al-Oqaily  for his helps.  

 

 

 

 

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