Role of the hepatic xanthine oxidase in thyroid dysfunction: effect of thyroid hormones in oxidative stress in rat liver

  • Keun Huh
  • Tae-Hyub Kwon
  • Jin-Sook Kim
  • Jon Min Park
Research Articles


The effect of thyroid hormones on the hepatic xanthine oxidase activity was studied in rats after the intraperitoneal injections of comthyroid (triiodotyronine: thyroxine=1 :4) at 0.3 mg/kg for 3 consecutive days. The aim of this study was to understand the precise mechanism of hyperthyroidism induced by oxidative stress. The concentration of lipid peroxides determined indirectly by the measurement of thiobarbituric acid reactants was increased in comthyroid treated rats. The hepatic glutathione content was decreased in comthyroid injected rat compared to the euthyroid state. It was also observed that the increment of xanthine oxidase activity has a profound role in oxygen radicals generation system in comthyroid treated rat. These findings suggest that the enhanced xanthine oxidase activity and depleting glutathione content in comthyroid treated rats result in pathophysiological oxidative stress including an increment of hepatic lipid peroxidation.

Key words

Xanthine oxidase Lipid peroxidation Comthyroid Hyperthyroidism 

Refrences Cited

  1. Ana, M. A., Susna, F. L., Juana, M. P. and Alberto, B., Brain chemiluminescence and oxidative stress in hyperthyroid rats.Biochem. J., 263, 273–277 (1989).Google Scholar
  2. Asayma, K., Dobashi, K., Hayashibe, H., Megate, Y. and Kato, K., Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rats: A possible mechanism of injury to heart and skeletal muscle in hyperthyroidism.Endocrinol., 121, 2112–2118 (1987).Google Scholar
  3. Asayma, K., Dobashi, K., Hayashibe, H. and Kato, K., Vitamin E protects against thyroxine-induced acceleration of lipid peroxidation in cardiac and skeletal muscle in rats.J. Nutr. Sci. Vitaminol., 35, 407–418 (1989).Google Scholar
  4. Bindoli, A., Cavallini, L., Rigobello, M. P., Coassin, M. and Lisa, F. D., Modification of the xanthine converting enzyme of perfused rat herat during ischemia and oxidative stress.Free. Radic. Biol. Med., 4, 163–167 (1988).PubMedCrossRefGoogle Scholar
  5. Chambers, D. E., Parks, D. A., Patterson, G., Roy, R., MoCord, J. M., Yoshida, S., Parrnley, L. F. and Downey, J. M., Xanthine oxidase as a source of free radical damage in myocardial ischemia.J. Mol. Cell. Cardiol., 17, 145–152 (1985).PubMedCrossRefGoogle Scholar
  6. Das, D. K., Engelman, R. M., Clement, R., Otani, H., Prasad, M. R. and Rao, P. S., Role of xanthine oxidase inhibitor as free radicals scavenger. A novel mechanism of action of allopurinol and oxypurinol in myocardial salvage.Biochem. Biophys. Res. Commun., 148, 314–319 (1987).PubMedCrossRefGoogle Scholar
  7. Della Corte, E. and Stirpe, F., The regulation of rat liver xanthine oxidase, involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme.Biochem. J., 126, 739–749 (1972).Google Scholar
  8. Fernandez, V., Barrientos, X., Kipreos, K., Valenzuela, A. and Videla, L. A., Superoxide radical generation, NADPH oxidase activity, and cytochrome P-450 content of rat liver microsomal fractions in experimental hyperthyroid state: relation to lipid peroxidation.Endocrinol., 117, 496–501 (1985).Google Scholar
  9. Fernandez, V., Llesuy, S., Solari, L., Kipreos, K., Videla, L. A. and Boveris, A., Chemiluminescent and respiratory responses related to thyroid hormone-induced liver oxidative stress.Free. Raidc. Res. Commun., 5, 77–84 (1988).CrossRefGoogle Scholar
  10. Fernandez, V. and Videla, L. A., Hepatic glutathione biosynthetic capacity in hyperthyroid rats.Toxicol. Lett., 89, 85–89 (1996).PubMedCrossRefGoogle Scholar
  11. Fernandez, V. and Videla, L. A., Effect of hyperthyroidism on the billary release of thiobarbituric acid reactants in the rat.Toxicol. Lett., 84, 149–153 (1996).PubMedCrossRefGoogle Scholar
  12. Griffith, O. W., Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine.Anal. Biochem., 106, 207–212 (1980).PubMedCrossRefGoogle Scholar
  13. Joseph, L., Skibba, R. H., Stadnicka, P. A. and Kalbfleisch, J. K., Lipid peroxidation caused by hyperthermic perfusion of rat liver.Biochem. Pharmacol., 40, 1411–1414 (1990).CrossRefGoogle Scholar
  14. Kuppusamy, P. and Zweier, J. L., Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation.J. Biol. Chem., 264, 9880–9884 (1989).PubMedGoogle Scholar
  15. Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J., Protein measurement with the Folin phenol reagent,J. Biol. Chem., 193, 265–275 (1951).PubMedGoogle Scholar
  16. Mano, T., Sinohara, R., Sawai, Y., Oda, N., Nishida, Y., Mokuno, T., Asano, K., Ho, Y., Kotake, M., Hamade, M., Nakai, A. and Nagasaka, A., Changes in lipid peroxidation and free radical scavengers in the brain of hyper and hypothyroid aged rats.J. Endocrinol., 147, 361–365 (1995).PubMedGoogle Scholar
  17. McCord, J. M., Oxygen-derived free radicals in postischemic tissue injury.New England J. Medi., 312, 159–163 (1985).Google Scholar
  18. Ohkawa, H., Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction.Anal. Biochem., 95, 351–358 (1979).PubMedCrossRefGoogle Scholar
  19. Parks, D. A. and Granger, D. N., Ischemia-induced vascular changes; role of xanthine oxidase and hydroxyl radicals.Am. J. Physiol., 245, G285–289 (1983).PubMedGoogle Scholar
  20. Parks, D. A. and Granger, D. N., Xanthine oxidase: Biochemistry, distribution and physiology.Acta Physiol. Scand. Suppl., 548, 87–99 (1986).PubMedGoogle Scholar
  21. Pereira, B., Costa-Rosa, L. F. B. P., Safi, D. A., Bechara, E. J. H. and Curi, R., Control of superoxide dismutase, catalase and glutathione peroxidase activities in rat lymphoid organs by thyroid hormones.J. Endocrinol., 140, 73–77 (1994).PubMedCrossRefGoogle Scholar
  22. Pessayre, D., Wandscheer, J. C., Cobert, B., Level, R., Degott, C., Batt, A. M., Martin, N. and Benhamou, J. P., Additive effects of inducers and fasting on acetaminophen hepatotoxicity.Biochem. Pharmacol., 29, 2219–2223 (1980).PubMedCrossRefGoogle Scholar
  23. Schwartz, H. L. and Oppenheimer, J. H., Physiologic and biochemical actions of thyroid hormone.Pharmacol. Ther., 3, 349–376 (1978).Google Scholar
  24. Seven, A., Swymen, O., Hatemi, S., Hatemi, H., Ylgit, G. and Candan, G., Antioxidant status in experimental hyperthyroidism: effect of vitamin E supplementation.Clin. Chim. Acta., 256, 65–74 (1996).PubMedCrossRefGoogle Scholar
  25. Siegers, C. P., Schutt, A. and Strubelt, O., Influence of some hepatotoxic agents on hepatic glutathione levels in mice.Clinical toxicology.Amsterdam, Excerpta Medica., 160–162 (1978).Google Scholar
  26. Tapia, G., Pepper, I., Smok, G. and Videla, L. A., Kupffer cell function in thyroid hormone-induced liver oxidative stress in the rat.Free. Radic. Res., 26, 267–279 (1997).PubMedCrossRefGoogle Scholar
  27. Tappel, A. L., Lipid peroxidation damage to cell components.Federation Proceedings, 32, 1870–1874 (1973).PubMedGoogle Scholar
  28. Turrens, J. F., Alexandre, A. and Lehninger, A. L., Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria.Arch. Biochem. Biophy., 237, 408–414 (1985).CrossRefGoogle Scholar
  29. Videla, L. A. and Fernandez, V., Thyroid calorigenesis and oxidative stress: modification of the respiratory burst activity in polymorphonuclear leukocytes.Braz. J. Med. Biol. Res., 27, 2331–2342 (1994).PubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 1998

Authors and Affiliations

  • Keun Huh
    • 1
  • Tae-Hyub Kwon
    • 2
  • Jin-Sook Kim
    • 2
  • Jon Min Park
    • 2
  1. 1.Department of Pharmacology, College of PharmacyYeungnam UniversityGyongsanKorea
  2. 2.Dept. of PharmacyYeungnam Medical CenterTaeguKorea

Personalised recommendations