Deneysel hipertiroidizmde α-lipoik asidin oksidatif stres parametreleri üzerine etkileri

Abstract

Amaç: Deneysel hipertiroidizmde α-lipoik asid (ALA)’ in karaciğer dokusunda prooksidan-antioksidan denge üzerine etkileri ile karaciğer fonksiyon testlerinin incelenmesi.

Yöntem: Prooksidan-antioksidan dengenin değerlendirilmesi için, reaktif oksijen ürünleri (ROS), malondialdehit (MDA), protein karbonil (PC), total antioksidan kapasite (FRAP)  ve glutatyon (GSH) düzeyleri ile süperoksit dismutaz, katalaz ve glutatyon peroksidaz aktiviteleri incelendi.  Ayrıca, histopatolojik incelemeler yapıldı. Hipertiroidi tablosu oluşturmak için T4 (12 mg/L) 10 hafta boyunca içme suyunda uygulandı. ALA [100 mg/kg/gün; % 0.2 [w/w]; diyette] deney süresinin son 5 haftasında uygulandı.

Bulgular: Karaciğerde oksidatif stresin arttığı görüldü. Hipertiroidili sıçanlarda ROS, MDA, PK düzeylerinde anlamlı artış bulundu. Ayrıca FRAP düzeylerinde artış ve GSH düzeylerinde azalma görüldü. ALA tedavisi, artan serum serbest T3 ve T4 düzeylerini düşürdü ve karaciğerde ROS, MDA ve PK düzeylerini anlamlı olarak azalmasına neden oldu. ALA uygulaması öncesi ve sonrasında serum karaciğer fonksiyon testlerinde bir değişiklik görülmedi.

Sonuç: Sonuçlarımız, ALA tedavisinin prooksidan-antioksidan dengedeki değişikliklerin düzelmesinde etkili olduğunu ve hipertiroidi tedavisinde destekleyici ajan olarak yararlı olabileceğini göstermektedir. 

Keywords

• prooksidan-antioksidan denge,hipertiroidizm,α-lipoik asid

Effects of α-lipoic acid on oxidative stress parameters in experimental hyperthyroidism

Abstract

Aim: To investigate the effects of α-lipoic acid (ALA) on prooxidant-antioxidant balance in liver tissue, as well as liver function tests in experimental hyperthyroidism.

Materials and Methods: For the evaluation of prooxidant-antioxidant balance, reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonyl (PC), ferric reducing antioxidant power (FRAP), glutathione (GSH) levels, and superoxide dismutase, catalase and glutathione peroxidase activities were determined. Histopathological examinations were also performed. Hyperthyroidism was induced by the administration of L-thyroxine [T4, 12 mg/L]  in drinking water for 10 weeks. The ALA [100 mg/kg/day; 0.2% (w/w) in diet] was administered in last 5 weeks of experimental period. 

Results: Oxidative stress in liver tissue from hyperthyroid rats was accentuated. Significant increases in hepatic ROS, MDA, and PC levels were found. Additionally, increased FRAP and decreased GSH levels were observed.  ALA treatment lowered the elevated serum free T3 and T4 levels and significantly decreased hepatic ROS, MDA and PC levels. Serum liver function tests in hiperthyroid rats before and after ALA treatment were not changed.

Conclusion: Our results indicate that ALA treatment was effective in the improvement of changes in prooxidant-antioxidant balance,  and may be useful as supportive agent for the treatment of hypertyroidism.

Keywords

• Proxidant-antioxidant balance,hyperthyroidism,α-lipoic acid

References

1. 1. Ichiki T. Thyroid hormone and atherosclerosis. Vascul Pharmacol. 2010;52:151-6.
2. 2. Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, et al. Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm. 2016;2016:6757154.
3. 3. Venditti P, De Rosa R, Di Meo S. Effect of thyroid state on susceptibility to oxidants and swelling of mitochondria from rat tissues. Free Radic Biol Med. 2003;35:485-94.
4. 4. Villanueva I, Alva-Sánchez C, Pacheco-Rosado J. The role of thyroid hormones as inductors of oxidative stress and neurodegeneration. Oxid Med Cell Longev. 2013;2013:218145.
5. 5. Das K, Chainy GB. Thyroid hormone influences antioxidant defense system in adult rat brain. Neurochem Res. 2004;29:1755-66.
6. 6. Lassoued S, Mseddi M, Mnif F, Abid M, Guermazi F, Masmoudi H, et al. A comparative study of the oxidative profile in Graves' disease, Hashimoto's thyroiditis, and papillary thyroid cancer. Biol Trace Elem Res. 2010;138:107-15.
7. 7. Subudhi U, Das K, Paital B, Bhanja S, Chainy GB. Alleviation of enhanced oxidative stress and oxygen consumption of L-thyroxine induced hyperthyroid rat liver mitochondria by vitamin E and curcumin. Chem Biol Interact. 2008;173:105-14.
8. 8. Asayama K, Dobashi K, Hayashibe H, Megata Y, Kato K. Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism. Endocrinology. 1987;121:2112-8. 9. Subudhi U, Chainy GB. Expression of hepatic antioxidant genes in l-thyroxine-induced hyperthyroid rats: regulation by vitamin E and curcumin. Chem Biol Interact. 2010;183:304-16.

9. 10. Panda S, Kar A. Annona squamosa seed extract in the regulation of hyperthyroidism and lipid-peroxidation in mice: possible involvement of quercetin. Phytomedicine 2007;14:799-805.
10. 11. Panda S, Kar A. Antithyroid effects of naringin, hesperidin and rutin in l-T4 induced hyperthyroid rats: possible mediation through 5'DI activity. Pharmacol Rep. 2014;66:1092-9.
11. 12. Gorąca A, Huk-Kolega H, Piechota A, Kleniewska P, Ciejka E, Skibska B. Lipoic acid - biological activity and therapeutic potential. Pharmacol Rep. 2011;63:849-58.
12. 13. Cimolai MC, Vanasco V, Marchini T, Magnani ND, Evelson P, Alvarez S. α-Lipoic acid protects kidney from oxidative stress and mitochondrial dysfunction associated to inflammatory conditions. Food Funct. 2014;5:3143-50.
13. 14. Suh JH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with [R]-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005;10:52-60.
14. 15. Yang RL, Li W, Shi YH, Le GW. Lipoic acid prevents high-fat diet-induced dyslipidemia and oxidative stress: a microarray analysis. Nutrition 2008;24:582-8. 16. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med. 1999;27:612-6.
15. 17. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–10.
16. 18. Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 1994;233:357-63.
17. 19. Benzie IFF, Strain JJ. The ferric reducing ability of plasma [FRAP] as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996;239:70-6.
18. 20. Beutler E, Duron O, Kelly BM. Improved method for determination of blood glutathione. J Lab Clin Med 1963;61:882-8.
19. 21. Worthington V. Catalase. In: Worthington Enzyme Manual: Enzymes and related biochemicals. NJ Worthington Biochem Corp. 1993:77-80.
20. 22. Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986;82:512-20.
21. 23. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70:158-69.
22. 24. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150:76-85.
23. 25. Uysal M, Koçak-Toker N, Doğru-Abbasoğlu S. Carnosine protection againist liver injury. In: Preedy VR, editör. Imidazole Dipeptides: Chemistry, Analysis, Function and Effects. The Royal Society of Chemistry, Cambridge. 2015. pp: 510-527.
24. 26. Andican G, Gelişgen R, Civelek S, Seven A, Seymen O, Altuğ T, et al. Oxidative damage to nuclear DNA in hyperthyroid rat liver: inability of vitamin C to prevent the damage. J Toxicol Environ Health A. 2004;67:413-20.
25. 27. Kumar N, Kar A, Panda S. Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats. Cell Biochem Funct. 2014;32:538-46.
26. 28. Pamplona R, Portero-Otín M, Ruiz C, Bellmunt MJ, Requena JR, Thorpe SR, et al. Thyroid status modulates glycoxidative and lipoxidative modification of tissue proteins. Free Radic Biol Med. 1999;27:901-10.