Skip to main content
Log in

Thyroid Hormone Influences Antioxidant Defense System in Adult Rat Brain

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The objective of the current study was to find out whether thyroid hormone influences antioxidant defense parameters of rat brain. Several oxidative stress and antioxidant defense parameters of mitochondrial (MF) and post-mitochondrial (PMF) fractions of cerebral cortex (CC) of adult rats were compared among euthyroid (control), hypothyroid [6-n-propylthiouracil (PTU)-challenged], and hyperthyroid (T3-treatment to PTU-challenged rats) states. Oxidative stress parameters, such as thiobarbituric acid-reactive substances (TBA-RS) and protein carbonyl content (PC), in MF declined following PTU challenge in comparison to euthyroid rats. On the other hand, when PTU-challenged rats were treated with T3, a significant increase in the level of oxidative stress parameters in MF was recorded. Hydrogen peroxide content of MF as well as PMF of CC was elevated by PTU-challenge and brought to normal level by subsequent treatment of T3. Although mitochondrial glutathione (reduced or oxidized) status did not change following PTU challenge, a significant reduction in oxidized glutathione (GSSG) level was noticed in PMF following the treatment. T3 administration to PTU-challenged rats had no effect on mitochondrial glutathione status. Total and CN-resistant superoxide dismutase (SOD) activities in MF of CC augmented following PTU challenge. CN-resistant SOD activity did not change when PTU-challenged rats were treated with T3. Although CN-sensitive SOD activity of PMF remained unaltered in response to PTU challenge, its activity increased when PTU-challenged rats were treated with T3. Catalase activity in PMF of CC of PTU-challenged rats increased, whereas the activity was decreased when hypothyroid rats were treated with T3. Similarly, total and Se-dependent glutathione peroxidase (GPx) activities of MF increased following PTU challenge and reduced following administration of T3. Se-independent GPx activity of MF and PMF and glutathione reductase activity of PMF decreased following PTU challenge and did not change further when rats were treated with T3. On the other hand, glutathione S-transferase activity of MF and PMF of CC did not change following PTU challenge but decreased below detectable level following T3 treatment. Results of the current investigation suggest that antioxidant defense parameters of adult rat brain are considerably influenced by thyroid states of the body.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Moutsatsou, P., Psarra, A. M. G., Tsiapara, A., Paraskevakou, H., Davaris, P., and Sekeris, C. E. 2001. Localization of glucocorticoid receptor in rat brain mitochondria. Arch. Biochem. Biophys. 386:69–78.

    Google Scholar 

  2. Lehninger, A. L., Nelson, D. L., and Cox, M. M. 1993. Principles of Biochemistry, CBS Publishers and Distributors, New Delhi, India.

    Google Scholar 

  3. Chance, B., Sies, H., and Boveris, A. 1979. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59:527–605.

    Google Scholar 

  4. Turrens, J. F., Alexandre, A., and Lehninger, A. L. 1985. Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch. Biochem. Biophys. 273:408–414.

    Google Scholar 

  5. Halliwell, B. and Gutteridge, J. M. C. 2001. Free Radicals in Biology & Medicine, Clarendon Oxford University Press, New York.

    Google Scholar 

  6. Tata, J. R., Emster, L., Lindberg, O., Arrhenius, E., Pedersen, S., and Hedman, R. 1963. The action of thyroid hormones at the cell level. Biochem. J. 86:408–428.

    Google Scholar 

  7. Satav, J. G. and Katyare, S. S. 1982. Effect of experimental thyrotoxicosis on oxidative phosphorylation in rat liver, kidney and brain mitochondria. Mol. Cell. Endocrinol. 28:173–189.

    Google Scholar 

  8. Ford, D. H. and Cramer, E. B. 1977. In iGrave, G. D. (ed.), Thyroid hormones and Brain Development, Raven, New York, p. 1.

    Google Scholar 

  9. Timiras, P. S. 1988. Thyroid hormones and the developing brain. In Meisam, E. and Timiras, P. S. (eds.), Handbook of Human Growth and Developmental Biology, Vol. 1 Part C, CRC Press Inc., Boca Raton, pp. 59–82.

    Google Scholar 

  10. Barker, S. B. and Klitgaard, H. M. 1952. Metabolism of tissues excised from thyroxine-injected rats. Endocrinology 170:81–86.

    Google Scholar 

  11. Sterling, K., Milch, P. O., and Brenner, M. A. 1977. Thyroid hormone action: The mitochondrial pathway. Science 197:996–999.

    Google Scholar 

  12. Schwartz, H. L. and Oppenheimer, J. H. 1978. Ontogenesis of 3,5-3_-triiodothyronine receptors in neonatal rat brain: dissociation between receptor concentration and stimulation of oxygen consumption by 3,5,3_-triiodothyronine. Endocrinology 103:943–948.

    Google Scholar 

  13. Katayre, S. S., Bangur, C. S., and Howland, J. L. 1994. Is respiratory activity in the brain mitochondria responsive to thyroid hormone action?: a critical re-evaluation. Neurochem. J. 302:857–860.

    Google Scholar 

  14. Obregon, M. J., Morreale de Escobar G.), and Escobar del Rey, F. 1978. Concentrations of triiodo-L-thyronine in the plasma and tissues of normal rats, as determined by radioimmunoassay: comparison with results obtained by an isotopic equilibrium technique, Endocrinology 103:2145–2153.

    Google Scholar 

  15. Oppenheimer, J. H., Schwartz, H. L., and Surks, M. I. 1974. Tissue differences in the concentration of triiodothyronine nuclear binding sites in rat: liver, kidney, pituitary, heart, brain, spleen and testis. Endocrinology 95:897–903.

    Google Scholar 

  16. Ahmed, M. T., Sinha, A. K., Pickard, M. R., Kim, K. D., and Ekins, R. P. 1993. Hypothyroidism in the adult rat causes brain regionspecific biochemical dysfunction, J. Endocrinol. 138:299–305.

    Google Scholar 

  17. Sarkar, P. K. and Ray, A. K. 2001. Involvement of L-triiodothyronine in acetylcholine metabolism in adult rat cerebral synaptosomes. Horm. Metab. Res. 33:270–275.

    Google Scholar 

  18. Dembri, A., Belkhiria, M., Michel, O., and Michel, R. 1983. Effect of short-and long-term thyroid ectomy on mitochondrial and nuclear activity in adult rat brain. Mol. Cell. Endocrinol. 33:211–223.

    Google Scholar 

  19. Paradies, G., Petrosillo, G., and Ruggiero, F. M. 1997. Cardiolipindependent decrease of cytochrome c oxidase activity in heart mitochondria from hypothyroid rats. Biochim. Biophys. Acta. 1319:5–8.

    Google Scholar 

  20. Mutvei, A. and Nelson, B. D. 1989. The response of individual polypeptides of the mammalian respiratory chain to thyroid hormone. Arch. Biochem. Biophys. 268:215–220.

    Google Scholar 

  21. Sahoo, A. and Chainy, G. B. N. 1997. Alterations in the activities of cerebral antioxidant enzymes of rat are related to aging. Int. J. Dev. Neurosci. 15:939–948.

    Google Scholar 

  22. Lambowitz, A. M. 1979. Preparation and analysis of mitochondrial ribosomes. Methods Enzymol. 59:421–433.

    Google Scholar 

  23. Ahmed, A. F., Whelan, J., Jequier, A. M., and Cummins, J. M. 2000. Torsion-induced injury in rat testes does not affect mitochondrial respiration or the accumulation of mitochondrial mutations. Int. J. Androl. 23:347–356.

    Google Scholar 

  24. Lowry, O. H., Rosebrough, N. J., Farr, A. Z., and Randall, R. J. 1951. Protein measurement with Folin-phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  25. Ohkawa, H., Ohishi, N., and Yagi, K. 1979. Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal. Biochem. 95:351–358.

    Google Scholar 

  26. Radi, R., Bush, K. M., and Freeman, B. A. 1993. The role of cytochrome c and mitochondrial catalase in hydroperoxide-induced heart mitochondrial lipid peroxidation. Arch. Biochem. Biophys. 300:409–415.

    Google Scholar 

  27. Pick, E. and Keisari, Y. 1981. Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages. Induction by multiple nonphagocytic stimuli. Cell. Immunol. 59:301–318.

    Google Scholar 

  28. Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A. G., Ahn, B. W., Shaltiel, S., and Stadman, E. R. 1990. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 186:464–478.

    Google Scholar 

  29. Griffith, O. W. 1980. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal. Biochem. 106:207–212.

    Google Scholar 

  30. Wudarczyk, J., Debsk, G., and Lenartowicz, E. 1996. Relation between the activities during disulfides and the protection against membrane permeability transition in rat liver mitochondria. Arch. Biochem. Biophys. 327:215–221.

    Google Scholar 

  31. Sedlak, J. and Lindsay, R. H. 1968. Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem. 25:192–205.

    Google Scholar 

  32. Cohen, G., Dembiec, D., and Marcus, J. 1970. Measurement of catalase activity in tissue extracts. Anal. Biochem. 34:30–38.

    Google Scholar 

  33. Das, K., Samanta, L., and Chainy, G. B. N. 2000. A modified spectrophotometric assay of superoxide dismutase using nitrite formation of superoxide radicals. Ind. J. Biochem. Biophys. 37:201–204.

    Google Scholar 

  34. Paglia, D. E. and Valentine, W. N. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70:158–169.

    Google Scholar 

  35. Massey, V. and Williams, C. H. 1965. On the reaction mechanism of yeast glutathione reductase. J. Biol. Chem. 240:4470–4481.

    Google Scholar 

  36. Habig, W. H., Pabst, M. J., and Jakoby, W. B. 1974. Glutathione-S-transferases. J. Biol. Chem. 249:7130–7139.

    Google Scholar 

  37. Gurrero, A., Pamplona, R., Portero-Otin, M., Barja, G., and Lopez-Torres, M. 1999. Effect of thyroid status on lipid composition and peroxidation in the mouse liver. Free. Radic. Biol. Med. 26:73–80.

    Google Scholar 

  38. Tamasy, V., Du, J. Z., Vallerga, A., Meisami, E., and Timiras, P. S. 1984. Suckling ability and maternal prolactin levels in hypothyroid rats. Horm. Behav. 18:457–464.

    Google Scholar 

  39. Pehowich, D. J. 1999. Thyroid hormone status and membrane n-3 fatty acid content influence mitochondrial proton leak. Biochim. Biophys. Acta. 1411:192–200.

    Google Scholar 

  40. Verhoeven, A. J., Kamer, P., Groen, A. K., and Tager, J. M. 1985. Effects of thyroid hormone on mitochondrial oxidative phosphorylation. Biochem. J. 226:183–192.

    Google Scholar 

  41. Pamplona, R., Portero-Otin, M., Ruiz, C., Bellmunt, M. J., Requena, J. R., Thrope, S. R., Baynes, J. W., Romero, M., Lopez-Torres, M., and Barja, G. 1999. Thyroid status modulates glycoxidative and lipoxidative modification of tissue proteins. Free Radic. Biol. Med. 27(7/8):901–910.

    Google Scholar 

  42. Wagner, K. R., Kleinholz, M., and Myers, R. E. 1989. Delayed neurologic deterioration following anoxia: Brain mitochondrial and metabolic correlates. J. Neurochem. 52:1407–1417.

    Google Scholar 

  43. Sims, N. R. and Blass, J. P. 1986. Expression of classical mitochondrial respiratory responses in homogenates of rat forebrain. J. Neurochem. 47:496–505.

    Google Scholar 

  44. Crantz, F. R., Silva, J. E., and Larsen, P. R. 1982. An analysis of the sources and quantity of 3,5,3_-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology 110:367–375.

    Google Scholar 

  45. Das, K. and Chainy, G. B. N. 2001. Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone, Biochim. Biophys. Acta. 1537:1–13.

    Google Scholar 

  46. Sims, N. R., Anderson, M. F., Hobbs, L. M., Kong, J. Y., Philips, S., Powell, J. A., and Zaidan, E. 2000. Impairment of brain mitochondrial function by hydrogen peroxide. Mol. Brain Res. 77:176–184.

    Google Scholar 

  47. Meister, A. and Anderson, M. E. 1983. Glutathione. Annu. Rev. Biochem. 52:711–760.

    Google Scholar 

  48. Ravindranath, V. and Reed, D. J. 1990. Glutathione depletion and formation of glutathione-protein mixed disulfide following exposure of brain mitochondria to oxidative stress. Biochem. Biophys. Res. Commun. 169:1075–1079.

    Google Scholar 

  49. Martensson, J., Goodwin, C. W., and Blake, R. 1992. Mitochondrial glutathione in hypermetabolic rats following burn injury and thyroid hormone administration: evidence of a selective effect on brain glutathione by burn injury. Metabolism 41:273–277.

    Google Scholar 

  50. Prohaska, J. R. 1980. The glutathione peroxidase activity of glutathione S-transferase. Biochim. Biophys. Acta. 611:87–98.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Das, K., Chainy, G.B.N. Thyroid Hormone Influences Antioxidant Defense System in Adult Rat Brain. Neurochem Res 29, 1755–1766 (2004). https://doi.org/10.1023/B:NERE.0000035812.58200.a9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000035812.58200.a9

Navigation