EFFECT OF HYPERTHYROIDISM ON LIPID AND ANTIOXIDANT STATUS IN WISTAR RATS

Deepmala Kaushik MSc. Life Sciences 105203998

THYROID GLAND

FUNCTIONS OF THE THYROID GLAND

Cellular Metabolic Activity A Carbohydrate metabolism B Lipid metabolism C Protein metabolism Increase the Transcription of large number of genes. Promote growth and development Increase blood flow and cardiac output Increase heart rate and heart strength

THYROID HORMONE DISEASES

HYPOTHYROIDISM HYPERTHYROIDISM

HYPERTHYROIDISM

Hyperthyroidism is a condition in which the thyroid gland makes too much thyroid hormone. The condition is often referred to as an "overactive thyroid.

EFFECTS OF HYPERTHYROIDISM
OXIDATIVE STRESS LIPID PEROXIDATION LOW SERUM CHOLESTROL(?)

OXIDATIVE STRESS

Oxidative stress is often defined as an imbalance of pro-oxidants and antioxidants, which can be quantified in humans as the redox state of plasma reduced glutathione (GSH)/oxidised glutathione(GSSG).

LIPID PEROXIDATION

Superoxide radical can lead to the formation of many other reactive species, including hydroxyl radicals, which can readily start the free radical process of lipid peroxidation (Chance et al. 1979).

BLOOD LIPID
TWO TYPES FATTY ACIDS CHOLESTROL

HYPERLIPIDEMIA

Increase in the lipids or lipoproteins in the blood causes hyperlipidemia.

ROLE OF THYROID HORMONE IN LIPID METABOLISM

LIPOGENESIS LIPID CLEARANCE

ANTIOXIDANTS

An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation reactions can produce free radicals.

VARIOUS ANTIOXIDANTS IN OUR BODY ARE:CATALASE SUPEROXIDE DISMUTASE GLUTATHIONE VITAMIN-A,C,E. VARIOUS PEROXIDASES SUCH AS GLUTATHIONE PEROXIDASE..etc

AIMS AND OBJECTIVES

To develop a rat model of hyperthyroidism To study the effect of hyperthyroidism on total lipid content in liver. To evaluate the antioxidant status of hyperthyroid rat To investigate the role of oxidative stress in hyperthyroid induced lipid mobilization

METHODOLOGY
ANIMALS The present study was conducted on thirteen rats , Wistar strain of rats of either sex weighing 17020gm.Animals were weighed every day to follow body weight gain or loss. They were divided into four groups. Rats of all the four groups were anaesthetize by an overdose of chloroform and sacrificed after 24 hours of the last dose.

TREATMENT WITH DRUG AND SOLUTION

Groups Group I(control) Group II (T4 treated) No. of rats 4 4 0.2mg/kg (L-thyroxine) 0.2mg/kg+20mg/kg (l-thyroxine+ ascorbic acid) 20mg/kg (ascorbic acid) Dose

Group III (T4+Vit C)

Group IV (Vit C perse)

The rats were sacrificed after 4 days of treatment

PARAMETERS STUDIED
T4 level by Fortress diagnostics ELISA kit Liver weight /body weight ratio Catalase activity (Teranishi et al., 1974). Blood glutathione peroxidase (Pippenger C.E et al., 1998) Total lipid content by (Zak et al., 1954)

STATISTICAL ANALYSIS

Data were expressed as meanSD. Students t-test was used for un-paired data. The values were considered significant at p<0.05. Microsoft Excel (version 97-2003,) for windows was used for statistical analysis

RESULTS

Plasma T4 levels
5

4.5
4 3.5 3 g/dl 2.5 2 T4 treated+vitamin C T4 treated control

1.5
1 0.5 0 Vitamin C per se

Data represent-meanSD. *P<0.05 from control

Increase in T4 levels is an indication of successful development of the rat model of hyperthyroidism at the dose of 0.2mg/kg.

Liver/Body Weight Ratio

70 60 Liver/Body weight ratio mg/g 50 40 30 20 Vitamin C per se 10 0 control T4 treated T4 treated+vitamin C

Data represent-meanSD. *P<0.05 from control

No significant change in the body weights of the four groups Liver/ body weight ratio was significantly increased in hyperthyroid Rats T4 and Vitamin C the liver body weight ratio was similar to normal rats and significantly less than the hyperthyroid rats

Total Catalase activity

2.5

mMH2O2min-1mg-1 protein

2
control 1.5 T4 treated

T4 treated+vitamin C
Vitamin C per se

0.5

0 1

Data represent-meanSD. *P<0.05 from control

ACTIVITY IS DECREASED IN HYPERTHYROID RATS IN COMPARISON TO NORMAL RATS Activity levels were similar to normal rats in T4+vitc

Blood glutathione peroxidase levels

300

250 control T4 TREATED 150 T4 treated+vitamin C 100 Vitamin C per se

200
g/mg

50

Data represent-meanSD. *P<0.05 from control

Blood glutathione peroxidase levels were significantly decreased in hyperthyroid rats in comparison to normal rats VITAMIN C is beneficial as a protective agent against oxidative stress induced by hyperthyroidism in rats.

TOTAL LIPID CONTENT

INCREASE IN THE LIPID CONTENT IN HYPERTHYROID RATS IN COMPARISON TO NORMAL RATS
* *
0.2 0.18 0.16 0.14 g/mg T4 treated 0.1 0.08 0.06 0.04 0.02 0 (g/10l) 0.12 control

DECREASE IN THE LIPID CONTENT IN HYPERTHYROID RATS IN COMPARISON TO NORMAL RATS

1 0.9 0.8 0.7 0.6 control T4 treated

Total Lipid Content (Liver)

Total Lipid Content (Blood)

Vitamin C per se

0.4 0.3 0.2 0.1 0

Data represent-meanSD. *P<0.05 from control

T4 treated+vitamin C

0.5

T4 treated+vitamin C
Vitamin C per se

CONCLUSION

From the present study it was concluded that indicators of oxidative stress are enhanced in hyperthyroid rats. In addition to this hyperthyroidism also promotes renal hypertrophy by lipogenesis,mobilisation of lipid from blood to liver. On treatment with vitamin C there was a amelioration in oxidative stress accompanied by normal liver body weight ratio, normal lipid contents suggesting a role of oxidative stress in thyroid induced hepatic hypertrophy which may be due to increased lipid mobilization and lipogenesis

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CONTD

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