7/31/2019 deep ppt

1/32

Deepmala Kaushik

MSc. Life Sciences

105203998

7/31/2019 deep ppt

2/32

7/31/2019 deep ppt

3/32

THYROID GLAND

7/31/2019 deep ppt

4/32

7/31/2019 deep ppt

5/32

7/31/2019 deep ppt

6/32

THYROID HORMONE DISEASES

HYPOTHYROIDISM

HYPERTHYROIDISM

7/31/2019 deep ppt

7/32

HYPERTHYROIDISM

Hyperthyroidism is a

condition in which the

thyroid gland makes

too much thyroidhormone.

The condition is often

referred to as an

"overactive thyroid.

7/31/2019 deep ppt

8/32

EFFECTS OF HYPERTHYROIDISM

OXIDATIVE STRESS

LIPID PEROXIDATION

LOW SERUM CHOLESTROL(?)

7/31/2019 deep ppt

9/32

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).

7/31/2019 deep ppt

10/32

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).

7/31/2019 deep ppt

11/32

BLOOD LIPID

TWO TYPES

FATTY ACIDS

CHOLESTROL

7/31/2019 deep ppt

12/32

HYPERLIPIDEMIA

Increase in the lipids or lipoproteins in the

blood causes hyperlipidemia.

7/31/2019 deep ppt

13/32

ROLE OF THYROID HORMONE IN LIPID

METABOLISM

LIPOGENESIS

LIPID CLEARANCE

7/31/2019 deep ppt

14/32

ANTIOXIDANTS

An antioxidant is a molecule that inhibits

the oxidation of other molecules.

Oxidation reactions can produce free radicals.

7/31/2019 deep ppt

15/32

VARIOUS ANTIOXIDANTS IN OUR BODY ARE:-

CATALASE

SUPEROXIDE DISMUTASE

GLUTATHIONE VITAMIN-A,C,E.

VARIOUS PEROXIDASES SUCH AS

GLUTATHIONE PEROXIDASE..etc

7/31/2019 deep ppt

16/32

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

7/31/2019 deep ppt

17/32

METHODOLOGY

ANIMALS

The present study was conducted on thirteenrats , Wistar strain of rats of either sex

weighing 17020gm.Animals were weighedevery day to follow body weight gain or loss.

They were divided into four groups.

Rats of all the four groups were anaesthetizeby an overdose of chloroform and sacrificedafter 24 hours of the last dose.

7/31/2019 deep ppt

18/32

TREATMENT WITH DRUG AND SOLUTION

Groups No. of rats Dose

Group I(control) 4

Group II (T4 treated) 4 0.2mg/kg(L-thyroxine)

Group III (T4+Vit C) 4 0.2mg/kg+20mg/kg(l-thyroxine+ascorbic acid)

Group IV (Vit C perse) 1 20mg/kg

(ascorbic acid)

The rats were sacrificed after 4 days of treatment

7/31/2019 deep ppt

19/32

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)

7/31/2019 deep ppt

20/32

Data were expressed as meanSD.

Students t-test was used for un-paired data.

The values were considered significant at

p

7/31/2019 deep ppt

21/32

RESULTS

7/31/2019 deep ppt

22/32

Increase in T4 levels is an indication of successfuldevelopment of the rat model of hyperthyroidism at the

dose of 0.2mg/kg.

Data represent-meanSD. *P

7/31/2019 deep ppt

23/32

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 normalrats and significantly less than the hyperthyroid rats

Data represent-meanSD. *P

7/31/2019 deep ppt

24/32

ACTIVITY IS DECREASED IN HYPERTHYROID RATS IN

COMPARISON TO NORMAL RATSActivity levels were similar to normal rats in T4+vitc

Data represent-meanSD. *P

7/31/2019 deep ppt

25/32

Blood glutathione peroxidase levels were significantly decreased inhyperthyroid rats in comparison to normal rats

VITAMIN C is beneficial as a protective agent against oxidative

stress induced by hyperthyroidism in rats.

Blood glutathione peroxidase levels

Data represent-meanSD. *P

7/31/2019 deep ppt

26/32

TOTAL LIPID CONTENT

INCREASE IN THE LIPID CONTENT IN

HYPERTHYROID RATS IN COMPARISON TONORMAL RATS

DECREASE IN THE LIPID CONTENT INHYPERTHYROID RATS IN COMPARISON TO

NORMAL RATS

Data represent-meanSD. *P

7/31/2019 deep ppt

27/32

CONCLUSION

From the present study it was concluded thatindicators of oxidative stress are enhanced inhyperthyroid rats.

In addition to this hyperthyroidism also promotes

renal hypertrophy by lipogenesis,mobilisation of lipidfrom blood to liver.

On treatment with vitamin C there was a ameliorationin oxidative stress accompanied by normal liver bodyweight ratio, normal lipid contents suggesting a role

of oxidative stress in thyroid induced hepatichypertrophy which may be due to increased lipidmobilization and lipogenesis

7/31/2019 deep ppt

28/32

REFERENCES

Ana Cachefo, Philippe Boucher, Caroline Vidon, Eric Dusserre, Fre DeRique Diraison,and Michel Beylot.Hepatic Lipogenesis and Cholesterol Synthesis in Hyperthyroid Patients.The Journal of Clinical Endocrinology & Metabolism(2001)86(11):53535357.

Araujo A.S., Seibel F.E., Oliveira U.O., Fernandes T., Llesuy S., Kucharski L., Bell-Klein A.(2011).Thyroid hormone-induced haemoglobin changes and antioxidant enzymes response inerythrocytes. Cell Biochem Funct.29(5).

Anthonisen , Holst ,Thomsen AA.(1960) Determination of cardiac output and otherhemodynamic data in patients with hyper- and hypothyroidism, using dye dilution technique.

Scandinavian Journal of Clinical and Laboratory Investigation..12472480. Celsing F, Blomstrand E, Melichna J, Terrados N, Clausen N,Lins PE & Jansson. E (1986)

Effect of hyperthyroidism on fibre-type composition,fibre area, glycogen content and enzymeactivity in human skeletal muscle. Clinical Physiology; 6 171181).

Capo LA & Sillau AH.(1983) The effects of hyperthyroidism on capillarity and oxidative capacityin rat soleus and gastroecnius muscles. Journal of Physiology; 342; 114.

Costantini F, Pierdomenico SD, De Cesare D, et al.(1998) Effect of thyroid function on LDLoxidation. Arteriosclerosis, Thrombosis, and Vascular Biology;18(5):732737.

Felix Vargas, Juan Manuel Moreno, Isabel Rodrguez-Gomez, Rosemary Wangensteen,Antonio Osuna1,Miriam A lvarez-Guerra and Joaqun Garca-Estan.

7/31/2019 deep ppt

29/32

CONTD

(2006)Vascular and renal function in experimental thyroid disorders. European Journal ofEndocrinology.;154; 197212.

Graettinger JS, Muenster JJ, Checchia CS, Grissom RL & Campbell JA.(1957).A correlationof clinical and hemodynamic studies in patients with hypothyroidism. Journal of ClinicalInvestigation.; 37; 501510.

Graettinger JS, Muenster JJ, Silverstone LA & Campbell JA.(1959). A correlation of clinicaland hemodynamic studies of patients with hyperthyroidism and with congestive heart failure.Journal of Clinical Investigation;40; 13161329.

Guyton and Hall.Textbook of medical physiology. (2011).Elsevier Saunders.,12. 931-942. Konstantinos, M., Maria V. Poulakou, Kosmas I Paraskevas. et al., (2007). Hyperthyroidism

is Associated with Increased Aortic Oxidative DNA Damage in a Rat Model. in vivo21: 1021-1026.

Klein I & Ojamaa K.Thyroid hormone and the cardiovascular system(2001)New EnglandJournal of Medicine. 344: 501509.

Klein I & Ojamaa K(1995). Thyroid hormone and blood pressure regulation.In Hypertension:Pathophysiology, Diagnosis and Management.Eds JH Laragh & BN Brenner. New York:Raven

Press Ltd, edn 2, pp 22472262. Klausen IC, Hegedus L, Hansen PS, Nielsen FE, Gerdes LU, Faergeman O.(1995)

Apolipoprotein(a) phonotypes and lipoprotein(a) concentrations in patients withhyperthyroidism. Journal of Molecular Medicine.;73(1):4146

7/31/2019 deep ppt

30/32

CONTD...

Larsen PR, Davis TF & Hay ID.The thyroid gland. In Williams Textbook of Endocrinology, edn 6,pp 389515.

Messarah M, Saoudi M, Boumendjel A, Boulakoud MS, Feki AE.(2011) Oxidative stressinduced by thyroid dysfunction in rat erythrocytes and heart. Environ Toxicol Pharmacol.;31(1):33-41.

Moreno, Isabel Rodrguez Gomez, Rosemary Wangensteen, Miriam Alvarez-Guerra,Juande Dios Luna, Joaqun Garca-Estan, and Felix Vargas. (2008). Tempol improves renalhemodynamics and pressure natriuresis in hyperthyroid rats Am J Physiol Regul Integr Comp

Physiol;294; R867R873.

Mohamadin AM, Hammad LN, El-Bab MF, Abdel Gawad HS(2007). Attenuation of oxidativestress in plasma and tissues of rats with experimentally induced hyperthyroidism by caffeic acidphenylethyl ester. Basic Clin Pharmacol Toxicol. Feb;100(2):84-90.

Melpomeni Peppa, ,* Grigoria Betsi, 1 and George Dimitriadis2 (2011) Lipid Abnormalities andCardiometabolic Risk in Patients with Overt and Subclinical Thyroid Disease J Lipids. ;

Nishitani H, Okamura K, Noguchi S, Inoue K, Morotomi Y, Fujishima M(1990). Serum lipid

levels in thyroid dysfunction with special reference to transient elevation during treatment inhyperthyroid graves disease.Hormone and Metabolic Research;22(9):490493.

Ozata M, Yildirimkaya M, Yilmaz K, et al.,(1998.) The effects of thyroid status on serumapolipoprotein A-I-containing lipoprotein particles. Hormone and Metabolic Research;30(4):217221.

7/31/2019 deep ppt

31/32

CONTD

P.Venditti ,R Pamplona,VAyala,R.De Rosa,G.Caldrone and S.Di Meo(2006). Differentialeffects of experimental and cold induced hyperthyroidism on factors inducing rat liver oxidativedamage. The journal of experimental biology209,817-825.

Uchida K, Nomura Y, Takase H, Tasaki T, Seo S, Hayashi Y, Takeuchi N.(1990) Effect ofvitamin C depletion on serum cholesterol and lipoprotein levels in ODS (od/od) rats unable tosynthesize ascorbic acid. J Nutr. ;120(10):1140-47.

Yavuz DG, Yksel M, Deyneli O, Ozen Y, Aydin H, Akalin S(2004). Association of serumparaoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-

suppressed nodular goitre patients. Clinical Endocrinology;61(4):515521 Ycel R, Ozdemir S, Daryerli N, Toplan S, Akyolcu MC,Yiit G(2009). Erythrocyte osmotic

fragility and lipid peroxidation in experimental hyperthyroidism. Endocrine. Dec;36(3):498-502. Zhu X, Cheng SY(2010). New insights into regulation of lipid metabolism by thyroid

hormone. Current Opinion in Endocrinology, Diabetes and Obesity;17(5):408-413. Jones DP.(2006) Redefining oxidative stress.Antioxid Redox Signal. ;(1865-79)

7/31/2019 deep ppt

32/32

THANK YOU