a preliminary study on the possible effect of chronic ... · mental exposure to cadmium co-mpounds,...

Egypt. J. Comp. Path. & Clinic. Path. Vol. 21 No. 1 (January) 2008; 31- 50

The protective role of vitamin C in reducing the pathological changes of cadmium chloride in albino rats: with special reference to thyroid

gland By

Nahla, A.G. Ahmed Refat and Ahmed, M.A. Omar* Departments Pathology and Forensic Medicine and Clinical Toxicology*,

Faculties of Veterinary Medicine and Medicine *, Zagazig University

SUMMARY The human and animal population are exposed to several xenobiotics. One

of them is cadmium, that may contaminate food, water and air. Fifty adult albino rats of both sex were divided into 5 equal groups to evaluate the adverse effects of cadmium chloride (CdCl2) on the kidneys, liver and thyroid gland and to evaluate the protective role of vitamin C. Gp.(1) was the control, Gps. (2,3,4) served as experimental control. Gp. (5) was the main experimental group. Gp. (1) was the nontreated control. Gp.(2) was orally given 1 ml distilled water / rat once daily. Gp. (3) was orally given 10 mg vitamin C / kg B.wt once daily. Gp. (4) was orally given 10 mg Cd Cl2 / kg B.wt once daily. Gp. (5) was given 10 mg vitamin C / kg B.wt and 10 mg Cd Cl2 / kg B.wt once daily. The treatments were given orally by the stomach tube for 16 weeks. Necropsy was performed at the end of the experiments. All the macroscopic abnormalities were recorded. Specimens from the kidneys, liver and thyroid gland were collected and prepared for microscopical examination. Other thyroid specimens were taken and prepared for electron microscopical examination.

Gp. (4), cadmium chloride group, revealed degenerative and necrotic changes in the renal epithelia which was subsequently, invaded and replaced by fibrous connective tissue and round cell infiltrations. Hypercellularity of the glomerular tufts besides perivascular edema and congestion of the renal blood vessels were observed. The liver showed degenerative changes and coagulative necrosis of the hepatocytes. Congestion of the hepatic blood vessels and lymphocytic infiltrations in the portal areas and in the interstitial tissue were observed. The thyroid gland revealed dilated follicles with pale eosinophilic vacuolated colloid and lined with flattened epithelium. The transmission electron microscopic examination of thyroid gland revealed apoptotic follicular cells, dilation of the endoplasmic reticulum and distroted Golgi apparatus and mitochondria. Gp. (5), Cd Cl2 and vitamin C group, showed milder lesions in comparison with gp. (4) which pointed out a partial protective role of vitamin C against CdCl2 toxicity.

The thyroid function test of gp. (4) showed a decrease in T3 and T4 and an increase in TSH which were statistically significant when compared with

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group 2 (positive control group). The presence of vitamin C in gp. (5) produced an improvement in the values of T3, T4 and TSH in comparison with gp. (4).

It can be concluded that, Cd Cl2 has adverse effects on the kidneys, liver and thyroid gland ,but vitamin C has a partial protective effect against these effects.

INTRODUCTION Humans and animals interact

with their environments on a daily basis and, as a consequence, are exposed to a broad spectrum of synthesized chemicals present in the food they eat, the air they bre-ath and the water they drink (Wa-de et al., 2000 and Bolkent et al., 2007). Cadmium has been relea-sed into the environment through human activities and is routinely found as a contaminant in tissues collected from the human popula-tion throughout the world (News-ome et al., 1995). Exposure to ca-dmium has increased because of its presence in fertilizers and in sewage sludge and also its Indus-trial use in cadmium nickel batt-eries (Ellis, 1995). Cadmium is unique among the other metals because of its toxicity at a very low dosage and long biologic half life (30 years in human) and its low rate of excretion from the bo-dy (Jones and Cherian, 1990). Although there is number of rep-orts on occupational and environ-mental exposure to cadmium co-mpounds, there is neither a safe nor a specific chelating agent for

acute or chronic cadmium intoxic-ation (Hideaki et al., 1997). Mu-rugavel and Pari (2007) observ-ed that, cadmium administered su-bcutaneously for 3 weeks to rats induced hepatic necrosis and sev-ere infiltration of the portal areas with inflammatory cells. Renal da-mage and congestion of the perir-enal blood vessels in guinea pigs given 1 mg cadmium / animal / day in drinking water for 12 we-eks and vitamin C can be effect-ive in the protection of cadmium-induced nephrotoxicity (Nagyova et al., 1994). Environmental contaminants may cause alterations in the funct-ion of endocrine system, thereby disrupting developmental and phy-siological functions in animals and humans (Brouwer et al., 1998). Chronic cadmium administration produced a significant increase in the median thyroid follicle colloid (Wade et al., 2002), deteriorate-on of the rough endoplasmic reti-culum and marked swelling of the mitochondria in the thyroid folic-ular epithelium of the rat (Pilat-Marcinkiewicz et al., 2002).

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Interestingly, several compo-unds have been shown to induce tolerance to cadmium-induced tis-sue injury (prevention of toxici-ty). These chemicals include met-als (zinc and nickel), steroid hor-mones (androgens and progestero-nes), antioxidants (ascorbate and tocopherol) (Waalkes and Goer-ing, 1990). Vitamin C is an esse-ntial antioxidant which plays a vi-tal role in protecting cells from damage of oxidizing agents (Gro-sicki, 2004). Peters et al (1995) reported that, vitamin C can alter the toxicity of cadmium.

MATERIALS AND METHODS This study was conducted on 50 normal adult albino rats of both sexes, weighing approximat-ely 160-200 gm each. They were obtained from the breeding animal house of Faculty of Medicine, Zagazig University. The rats were divided into 5 equal groups (Table 1). Gp.(1) was the non treated control group. Gps. (2, 3 and 4) were the experimental control. Each rat of gp. (2) was orally giv-en l ml distilled water once a day. Each rat of gp. (3) was orally given vitamin C, obtained from ADWIC (10 mg/kg. B.wt. dissol-ved in 1 ml distilled water) once a day (Sinha and Bose, 1992). Ea-ch rat of gp.(4) was orally given Cd CI 2 , obtained from El-Nasr Pharmaceutical Chemical Compa-ny (10 mg / kg. B.wt. dissolved in 1 ml of distilled water) once a day (Baranski et al., 1982). Each rat of gp.(5),experimental, was orally given vitamin C (10 mg/ kg. B.wt.) once a day, then CdCl2 was orally given at a dose of 10 mg/kg B.wt. once a day. The treatments were orally given by the stomach tube for 16 weeks.

The objective of the present

study was to investigate the path-ologic effects of cadmium chlori-de on the kidneys, liver and thyr-oid glands with special reference to the ultrastructural feature of the thyroid gland, besides the evaluat-ion of the thyroid function by measuring serum tri-iodothyroni-ne (T3), thyroxin (T4) and thyroid stimulating hormone (TSH). Mor-eover, the role of vitamin C in protecting the kidneys, liver and thyroid gland against the lesions induced by of cadmium chloride, if found, was considered.

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Table (1): Experimental design.

Oral treatments

Gps. No. of rats Design Distilled

water, 1 ml/rat

Vitamin C, 10 mg/kg

B.wt

CdCl2, 10 mg/kg B.wt

No. of sacrificed rats, 16

weeks PA1 10 Control - - - 10 2 10 + - - 10 3 10 - + - 10 4 10

Experi-mental control - - + 10

5 10 Experi-mental - + + 10

Total 50 50

PA = Post administration. No. = Number.

A-Thyroid Function Tests: Venous blood samples were obtained from all the animals by means of capillary glass tubes fr-om the retro-orbital plexus, under light anaesthesia at the end of ex-periment according to the proc-edure described by Schemere (1967). The collected blood samp-les were incubated at 37°C until blood clotted, then centrifuged to separate the serum for the deter-mination of triiodothyronine (T3), thyroxin (T4) and thyroid stimula-ting hormone (TSH) concentrati-ons. T3 and T4 were determined using radioimmunoassay kits (RIA) according to Larsen (1981) and Lehotay et al. (1982). Immu-nometric assay of TSH was done according to Kwiatkowski et al. (1990).

B- Histopathological examinati-on:

After taking the blood sampl-es, necropsy was performed and all the macroscopic abnormalities were recorded. Specimens from the kidneys, liver and thyroid gl-ands were obtained and fixed in 10% neutral buffered formalin so-lution. Paraffin sections of 5 µ th-ickness were prepared and stained with Haematoxylin (H) and Eosin (E) for light microscopic examin-ation (Bancroft and Steven, 1996). Other thyroid specimens were taken and dissected by sharp blade into very small blocks for electron microscopic processes. These small blocks were fixed in 2.5 % glutaraldehyde overnight. The tissue was then rinsed in 1.5% phosphate buffer (pH 7.35) and fixed in osmium tetroxide for

34


one hour. The tissue was dehyd-rated and embedded in Epon arl-dite resin (Hayat, 1989). Ultrath-in sections were obtained , stained with uranyl acetate and lead citra-te and then were examined by transmission electron microscope (JEOL 1000 X) in Zagazig Unive-rsity, Electron Microscope Centre. Photographs were taken, develop-ed and printed. C- Statistical Analysis: The collected results were computerized for statistical analy-sis by using Epi-lnfo (version 6.1) software statistical package (WHO, 1994). Comparing the means of T3, T4 and TSH was done by using t-test and analysis of variance (ANOVA). The least significant differences were calcu-lated by using the SPSS statistical package (SPSS, 1997).

RESULTS A-Pathological findings: Group (4): (given 10 mg CdCl2/ kg B.wt). The kidneys were macrosco-pically slightly enlarged. Microscopically, the kidneys rev-ealed congestion (fig. 1) and thic-kening of the wall of the renal bl-ood vessels with perivascular ede-ma (Fig. 2). Periglomerular prolif-eration of fibrous connective tiss-ue, infiltrated with round cells (fig. 3), was observed, which sub-sequently invaded and replaced

the renal parenchyma (fig. 4). Hy-percellularity of the glomerular tufts (fig. 5) was seen. Degene-rated renal tubules in the form of cloudy swelling and hydropic de-generation were detected. Some renal tubules showed coagulative necrosis in their lining epithelium.

The liver was macroscopic-ally slightly congested.

Microscopically, congestion of the hepatic sinusoids, associa-ted with pressure atrophy of some hepatocytes (fig. 6) was observed. The portal areas showed congest-ed blood vessels and were infiltra-ted with round cells (fig. 7) mos-tly lymphocytes. Focal coagulati-ve necroses were encountered and represented by Karyolysis (fig. 8). Interstitial aggregations of lymph-ocytes focally replaced the hepat-ic parenchyma (fig. 9). Vacuolati-on of the hepatocytes was detect-ed. These vacuoles were sharp empty or contained pale eosino-philic materials.

The thyroid gland, was macroscopically normal.

Microscopically, some thyro-id follicles were dilated with pale eosinophilic vacuolated colloid and lined with flattened epitheli-um (fig. 10). Under electron microscope, the thyroid follicular cells showed apoptosis, dilatated endoplasmic reticulum and distor-ted Golgi apparatus and mitoch-

35


ondria (fig. 11). Distortion and disruption of thyroid follicular ar-chitecture were seen.

B- Thyroid Function Tests Serum T3 (ng/dL),T4 (µg/dL) and TSH (µU/ dL)were estimated in the 5 studied groups and the re-sults were tabulated in (tables, 2-8). Table (2) shows no significant difference between the control and the experimental control gro-ups, so only the results of the ex-perimental control group will be used for comparison. Gps. (2 and 3) showed no abnormal findings, while gp. (4) displayed a signific-ant decrease in T3 and T4 and a significant increase in TSH when compared with gp.(2) (P<0.001). Gp. (5) showed a significant incr-ease in the mean values of T3 and T4 (77 ± 8.767, 4.194 ± 0.524) when compared with gp.(4) (70 ± 9.743, 3.671 ± 0.681) respectively with P<0.05. There was a signific-ant decrease in the mean value of TSH in gp. (5) (1.400 ± 0.183) in comparison to group 4 (1.528 ± 0.197) with P< 0.05.

Gp. (5): (given 10 mg CdCl2/kg

B.wt and 10 mg vitamin C /kg B.wt).

No gross lesions were recor-ded in the collected organs. Mi-croscopically, the kidneys showed mild congestion of the intertubu-lar blood vessels, and few round cell infiltration among the renal tubules (fig. 12). The liver revea-led congestion of the hepatic blo-od vessels (fig. 13) without infla-mmatory cells. The thyroid gland revealed normal thyroid follicul-es, lined by cuboidal epithelium and filled with evenly stained colloid (fig. 14). Milder ultrastru-ctural changes were seen in com-parison with group (4). Such cha-nges were represented by dilated endoplasmic reticulum and less distortion of the mitochondria (Fig. 15). The addition of vitamin C to

CdCl2 in gp. (5) produced a signi-ficant increase in the function of the thyroid gland when compared with gp. (4). Gp. (5) was still suffering hypofunction of the thy-roid gland, when compared with gp. (2).

Gp. (1) (control that was left without treatment), Gp. (2): (giv-en 1 ml distilled water / rat) and Gp. (3) (given 10 mg vitamin C / kg B.wt) showed neither gross nor microscopical lesions. Ultrastruct-ural, the thyroid gland revealed normal nuclei, endoplasmic retic-ulum and mitochondria (fig. 16).

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Figs. (1-4): Gp. (4), Kidney:

1- Severely congested blood vessel (thin arrow) and cloudy swelling of

the epithelial lining of some renal tubules (thick arrow) ,H & E., x

1200.

2- Perivascular edema (thin arrow) and thickening of the wall of the

blood vessel (thick arrow) , H & E., x300.

3- Periglomerular proliferation of fibrous connective tissue infiltrated

with round cells (arrow), H & E., x1200.

4- Focal replacement of the renal parenchyma by fibrous connective

tissue and lymphocytes (arrow), H & E., x1200.

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Figs. (5-8): Gp. (4):

5- Kidney: peritubular congestion (thin arrow) and hypercellularity of the

glomerular tufts (thick arrow) ,H & E., 300.

6- Liver: congestion of hepatic sinusoids (arrow) associated with pressure

atrophy of adjacent hepatocytes ,H & E., x300.

7-Liver: portal area with congested blood vessel and few leukocytic

infiltration thin arrow) besides focal coagulative necrosis of the

hepatocytes (thick arrow), H & E. x300.

8- Liver: high power of fig. (7) to show the coagulative necrosis of

hepatocytes represented by karyolysis (arrow), H & E. x1200.

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Figs. (9-11): Gp. (4): 9- Liver : focal interstitial aggregation of round cells (arrow),

H & E., x300. 10- Thyroid gland: dilated thyroid follicles with pale eosinophilic

vacuolated colloid (arrow) , H & E. x300

11- A transmission electron micrograph of thyroid gland: apoptosis “N”, dilated fragmented rough endoplasmic reticulum (R) and distorted Golgi apparatus (G) and mitochondria (M),

EM, x 8000. Fig. 12- Kidney of Gp. (5): mild congestion of intertubular blood vessels

(arrow) and few round cell infiltration among the renal tubules, H & E., 300.

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Fig. (13-15): Gp. (5): 13- Liver: congestion of the hepatic blood vessel (arrow),

H & E. x 300. 14-Thyroid gland: normal thyroid gland filled with evenly stained colloid

(arrows), H & E., x 300.

15- A transmission electron micrograph of thyroid gland: dilated endoplasmic reticulum (R) and distorted mitochondria (M),

EM., x 8000. Fig. 16- A transmission electron micrograph of thyroid gland of control

group: normal nuclei (N) mitochondria (M), Golgi apparatus (G) and rough endoplasmic reticulum (R) ,

EM., x 8000.

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Table (2): Means (X), and standard deviations (SD) of triiodothyronine (T3) tetraiodothyronine (T4) and thyroid stimulating hormone (TSH) in the rats of group l (-ve control group) and group 2 (Distilled water group).

Group 1 Group 2 X SD X SD P-value

T3 (ng/dL) 82.315 11.857 82. 150 11.975 0.171

T4( µg/dL) 5.33 0.989 5.27 0.996 0.115

TSH(µU/dL) 1.243 0.175 1.257 0.177 0.312

The number of rats in each group = 10 rats. There is no significant difference between negative and positive control groups. Table (3): Means (X),standard deviations(SD) and F-test of triiodothyronine

(T3) in the rats of studied groups 2, 3, 4 and 5.

Groups X±SD Range ng/dl

2 ( Distilled water group) 82.160 ± 11.965 61-105

3 (Vit. C group ) 83.640 ± 9.864 60-101

4 ( CdCl2 group) 70.0 ± 9.743 58-86

5 (CdCl2 & Vit. C group) 77.0 ± 8.767 59-94

F test

P value

7.462

0.0002

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Table (4): Least significant difference (LSD) for comparison of serum triiodothyronine (T3) in gps. (2, 3, 4 and 5).

Groups 2

(Distilled water group)

3 (Vit.C group)

4 (CdCl2 group )

5 (CdCl2 & Vit.

C group) 2 (Distilled water group) P= - 0.154 (NS) 0.0003 ** 0.098 (NS)

3 (Vit. C group ) P= - - 0.0008 ** 0.112 (NS)

4 (CdCl2 group ) P= - - - 0.042 *

5 (CdCl2 & Vit. C group) P= - - - -

P = Probability LSD: 6.394 *: Significant ( P < 0.05) NS: Non signifiant. (P > 0.05) ** : Highly significant (P < 0.001) Table (5): Means (X), standard deviations (SD) & F-test of triiodothyronine

(T4) in gps. (2, 3, 4 and 5).

Groups X±SD Range µg/dl

2 ( Distilled water group) 5.26±0.986 3.5-7.5

3 (Vit. C group ) 5.385±0.892 3.5-6.8

4 (CdCl2 group) 3.671±0.681 3.0-5.5

5(CdCl2 & Vit. C group) 4.194±0.524 3.5-5.6

F test

P value

22.280

0.0001

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Table (6): Least significant difference (LSD) for comparison of serum

triiodothyronine (t4) in the rats of studied gps 2, 3, 4 and 5.

Groups

2 (Distilled

water group)

3 (Vit.C group)

4 (CdCl2 group )

5 (CdCl2& Vit. C

group)

2 (Distilled water group) P= - 0.215 (NS) 0.0003 ** 0.037 *

3 (Vit. C group ) P= - - 0.0007 ** 0.025 *

4 (CdCl2 group ) P= - - - 0.041 *

5 (CdCl2 & Vit. C group ) P= - - - -

P = Probability LSD: 0.4999 NS: Non signifiant. (P > 0.05) *: Significant (P < 0.05) ** : Highly significant (P < 0.001) N.B: Number of rats in each group = 10 rats Table (7): Means (X), standard deviations (SD) & F-test of thyroid

stimulating hormone (TSH) in gps (2, 3, 4 and 5).

Groups X±SD Range Ug/dl

2 ( Distilled water group) 1.258±0.176 0.86-1.47

3 (Vit. C group ) 1.217±0.138 0.91-1.42

4 ( Cd Cl 2 group) 1.528±0.197 1.10-1.76

5( Cd Cl 2 & Vit. C group) 1.400±0.183 1.00-1.70

F test

P value

14.01

0.0001

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Table (8): Least Significant Difference (LSD) for comparison of thyroid stimulating hormone (TSH) in gps ( 2, 3, 4 and 5).

Groups

2 (Distilled

water group)

3 (Vit. C group)

4 (CdCl2 group )

5 (CdCl2& Vit.

C group )

2 (Distilled water group) P= - 0.084 NS 0.0007 ** 0.034 *

3 (Vit. C group ) P= - - 0.0005 ** 0.017 *

4 (CdCl2 group ) P= - - - 0.039 *

5 (CdCl2 & Vit. C group) P= - - - -

P = Probability LSD: 0.1073 NS: Non signifiant. (P > 0.05) *: Significant (P < 0.05) ** : Highly significant (P < 0.001) N.B: Number of rats in each group = 10 rats

DISCUSSION Heavy metals, such as cadmi-um, pose a number of environm-ental problems in addition to being detrimental to human and animal health (Warren et al., 2000). This study showed that, the cadmium chloride revealed degenerative and necrotic changes in the renal epit-helia which was subsequently repl-aced by fibrous connective tissue and round cells. Hypercellularity of the glomerular tufts, besides conge-stion of the renal blood vessels were observed. Thickening of the renal blood vessels and perivasc-ular edema were seen. The previo-us lesions are in partial agerement with Horiguchi et al. (2006) and Thijssen et al. (2007) who noticed

proximal tubular damage of the rat and mouse kidneys. The animals were given cadmium chloride in the drinking water and by injection respectively. Gubrelay et al. (2004) showed congestion at corti-comedullary junction and necrosis of the renal tubular epithelia of kid-neys in rats exposed to 0.5 and 1 mg cadmium chloride for 3 days. The liver showed focal coagulative necrosis and degenerative changes of the hepatocytes. Congestion of the hepatic blood vessels and lym-phocytic infiltrations in the portal areas and in the interstitial tissue were observed. The achieved resul-ts are in partial concurrence with Gubrelay et al. (2004) and Kayu et al. (2006). They found vacuolar

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degeneration in the hepatocytes and congestion of the hepatic blood vessels. The aforementioned lesi-ons in the kidneys and liver may be attributed to the direct effects of the cadmium chloride or its active metabolites on the renal and heap-tic tissue. Newairy et al. (2007) reported that cadmium induced he-patotoxicity due to its active stress by increasing the level of free rad-icals and decreasing the antioxidant level. Microscopically the thyroid of the rats in gp. (4) revealed dila-ted thyroid follicles with pale eosi-nophilic vacuolated colloid which led to disruption of the thyroid foll-icular architecture. This result is similar to that obtained by Wade et al. (2002). They found a significant increase in the median thyroid foll-icle colloid cross sectional area. The transmission electron micros-copic study of the thyroid gland of cadmium chloride group revealed apoptosis, dilatation of the endopl-asmic reticulum and distorted Golgi apparatus and mitochondria. These findings are in agreement with Yoshizuka et al. (1991) who found that, the electron microsco-pic examination of the thyroid gla-nds of rats exposed to cadmium showed deterioration of the rough-surfaced endoplasmic reticulum and marked swelling of the mitoch-ondria of the thyroid follicular epit-helium. They added that the accu-mulation of cadmium in the mitoc-hondria of the thyroid follicular

epithelium may disturb the oxidat-ive phosphorylation of this orga-nelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones. Gp. (5) showed milder lesi-ons than gp. (4). Mild congestion of the renal blood vessels and a few leukocytic infiltration were seen in the kidneys. The liver showed mild congestion of the hepatic blood ve-ssels, meanwhile, the thyroid gland showed nearly normal microsco-pical picture. The previous results coincide with Shiraishi et al. (1993) who recorded that the pre-treatment of rats with ascorbic acid decreased the hepatic toxicocis produced by cadmium. Nagyova et al. (1994) showed that vitamin C can be effective in the protection of cadmium induced nephrotoxicity. Sato et al. (1990) and Grosicki (2004) recorded that vitamin C is an excellent antioxidant. It was eff-ective in reducing the toxic effects of cadmium, through inhibition of lipid peroxidation (Peters et al., 1995) and increase the activities of antioxidant enzymes (Newairy et al., 2007). The thyroid function tests sho-wed that, gp.(4) exhibited a stati-stically significant decrease in both the serum T3 and T4 (P<0.001) and a statistically significant incre-ase in TSH (P<0.001). These resu-

45


lts are consistent with Levesque et al. (2003) who reported that the environmental exposure of fish to Cd decrease of the plasma T4 and T3 with structural alteration in the thyroid follicle epithelium. Pavia Junior et al. (1997) found that, T4 and T3 concentrations in cadmium chloride (CdCl2)-treated rats were significantly (P<0.01) decreased. The environmental contaminants, like cadmium, have been shown to cause a significant toxicity to the hypothalamic-pituitary-thyroid axis in laboratory animal studies with significantly increased TSH (Wade et al., 2002). Lafuente et al. (1997) reported that the subchronic CdCl2 administration for 14 days led to an increase in the level of TSH in adult male albino rats. Shupnik et al. (1986) reported that the TSH secretion by the pituitary gland is inversely related to the th-yroid hormone levels that serve as the basis for feedback control of the circulating thyroid hormone. Group (5) showed an increase in the mean values of the T3 and T4 and a reduction in the mean value of the TSH in comparison with group 4 (CdCl2 only) (P<0.05). The results showed the ability of vit-amin C to improve the disturbance of the thyroid function caused by CdCl2 but not to the basal level. The results are in line with previo-usly reported work in vivo exp-eriments, which revealed that, the

human equivalent therapeutic dose (10 mg/kg body weight / day) of vitamin C could reduce the toxin-induced damage, but failed to restore the control level (Sinha and Bose, 1992). Similar findings were observed in individuals expo-sed to environmental toxins and recovered faster in the presence of high vitamin C status (Kato et al., 1981). The current results are consistent with Gupta and Kar (1998) who reported that, the administration of Cd to Swiss male mice induced thyroid dysfunction and lipid peroxidation leading to a decrease in the serum concentra-tions of the thyroid hormones and hepatic type I iodothyronine 5-Monpdeiodinase (5 D-I) activity and an increase in the level of lipid peroxidation. The metal-induced a decrease in the hepatic 5D-I activity, but the serum T3 conc-entration was restored by treatment with ascorbic acid. Finally, it could be concluded that, cadmium chloride has adverse effects on the kidneys, liver and thyroid gland. Meanwhile, vitamin C has a partial protective effect against this effect. People exposed to cadmium should be advised to take regular doses of vitamin C to decrease the metal adverse effects on the kidneys, liver and thyroid gland.

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