Miler, E.A.; Ríos de Molina, M. del C.; Domínguez, G.; Guerra, L.N. "Thyroid hormone effect in human hepatocytes" (2008) Redox Report. 13(4):185-191
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We have already demonstrated that a combined treatment of methimazole and an antioxidant mixture improved the condition of hyperthyroid patients both biochemically and clinically. Elevated thyroid hormone levels might trigger signs and symptoms of hyperthyroidism through the increase of free radicals. To study the direct effect of thyroid hormone on cellular markers of oxidative stress, we carried out in vitro assays in which 0.1-20.0 nM T3 (6.5-1300.0 ng/dl) doses were added to culture media of the human hepatocyte cell line Hep G2 for 1-24 h. T3 increased malondialdehyde (MDA) and intracellular oxidized glutathione (GSSG) levels; SOD activity was also higher with hormone treatment, whereas catalase and glutathione peroxidase activities showed no variation at different T3 doses and during all experimental times. When ascorbic acid was added to the culture, the MDA level decreased and SOD activity was increased. With higher doses of T3 (e.g. 200 nM), cell death occurred (69% of apoptotic cells). The increase in SOD activity was not enough to overcome the effect of T3 since MDA and GSSG remained high during a 24-h experiment. We showed a beneficial effect of ascorbic acid when cells were exposed to a T3 dose of 20 nM, a higher level of hormone than that achieved in hyperthyroidism. © 2008 W. S. Maney and Son Ltd.


Documento: Artículo
Título:Thyroid hormone effect in human hepatocytes
Autor:Miler, E.A.; Ríos de Molina, M. del C.; Domínguez, G.; Guerra, L.N.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, 1428 Buenos Aires, Argentina
Palabras clave:Human hepatocytes; Oxidative stress; Thyroxine; ascorbic acid; catalase; free radical; glutathione disulfide; glutathione peroxidase; liothyronine; malonaldehyde; superoxide dismutase; antioxidant activity; apoptosis; article; cell culture; cell level; cell strain HepG2; controlled study; cytotoxicity; enzyme activity; human; human cell; in vitro study; liver cell; oxidative stress; priority journal; Antioxidants; Ascorbic Acid; Catalase; Cell Line, Tumor; Dose-Response Relationship, Drug; Glutathione Disulfide; Glutathione Peroxidase; Hepatocytes; Humans; Malondialdehyde; Superoxide Dismutase; Triiodothyronine
Página de inicio:185
Página de fin:191
Título revista:Redox Report
Título revista abreviado:Redox Rep.
CAS:ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; catalase, 9001-05-2; glutathione disulfide, 27025-41-8; glutathione peroxidase, 9013-66-5; liothyronine, 6138-47-2, 6893-02-3; malonaldehyde, 542-78-9; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; Antioxidants; Ascorbic Acid, 50-81-7; Catalase, EC; Glutathione Disulfide, 27025-41-8; Glutathione Peroxidase, EC; Malondialdehyde, 542-78-9; Superoxide Dismutase, EC; Triiodothyronine, 6893-02-3


  • Feng, X., Jiang, Y., Meltzer, P., Yen, P.M., Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA microarray (2000) Mol Endocrinol, 14, pp. 947-956
  • Videla, L.A., Energy metabolism, thyroid calorigenesis, and oxidative stress: Functional and cytotoxic, consequences (2000) Redox Report, 5, pp. 265-275
  • Venditti, P., Pamplona, R., Ayala, V., De Rosa, R., Caldarone, G., Di Meo, S., Differential effects of experimental and cold-induced hyperhyroidism on factors inducing rat liver oxidative damage (2006) J Exp Biol, 209, pp. 817-825
  • Videla, L.A., Sir, T., Wolff, C., Increased lipid peroxidation in hyperthyroid patients: Suppression by propylthiouracil treatment (1988) Free Radic Res Commun, 5, pp. 1-10
  • Lissi, E.A., Salim-Hanna, M., Sir, T., Videla, L.A., Is spontaneous urinary visible chemiluminescence a reflection of in vivo oxidative stress? (1992) Free Radic Biol Med, 12, pp. 317-322
  • Komosinska, V.K., Olczyk, K., Kucharz, E.J., Marcisz, C., Winsz-Szcotka, K., Kotulska, A., Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves' disease during therapy (2000) Clin Chim Acta, 300, pp. 107-117
  • Mano, T., Shinohara, R., Iwse, K., Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders (1997) Horm Metab Res, 29, pp. 351-354
  • Guerra, L.N., Moiguer, S., Karner, M., Rios de Molina, M.C., Sreider, C.M., Burdman, J.A., Antioxidants in the treatment of Graves' disease (2001) IUBMB Life, 51, pp. 105-109
  • Gomes, L.F., Lorente, S., Simon-Giavarotti, K.A., Areco, K.N., Araujo-Peres, C., Videla, L.A., Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations (2004) Molecular Aspects of Medicine, 25, pp. 183-190. , Azzi A, ed, New York: Elsevier
  • Morel, Y., Barouki, R., Repression of gene expression by oxidative stress (1999) Biochem J, 342, pp. 481-496
  • Jaswal, S., Metha, H.C., Sood, A.K., Kaur, J., Antioxidant status in rheumatoid arthritis and role of antioxidant therapy (2003) Clin Chim Acta, 338, pp. 123-129
  • Bustamante, J., Guerra, L.N., Bredeston, L., Mordoh, J., Boveris, A., Melanin content and hydroperoxide metabolism in human melanoma cells (1991) Exp Cell Res, 196, pp. 172-176
  • Buettner, G.R., Jurkiewicz, B.A., Catalytic metals, ascorbate and free radicals: Combinations to avoid (1996) Radiat Res, 145, pp. 532-541
  • Guerra, L.N., Rios de Molina, M.C., Miler, E., Moiguer, S., Karner, M., Burdman, J.A., Antioxidants and methimazole in the treatment of Graves' disease: Effect on urinary malondialdehyde levels (2005) Clin Chim Acta, 352, pp. 115-120
  • Abuja, P.M., Albertini, R., Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins (2001) Clin Chim Acta, 306, pp. 1-17
  • Baker, M.A., Cerniglia, G.J., Zaman, A., Microtiter plate assay for measurement of glutathione and glutathione disulfide in large number of biological samples (1990) Anal Biochem, 190, pp. 360-365
  • Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254
  • Rice Evans, C.A., Diplock, A.T., Symnos, M., Techniques in free radical research (1991) Laboratory Techniques in Biochemistry and Molecular Biology, 22, pp. 199-201. , Burdon RH, van Knippengberg PH, eds, New York: Elsevier
  • Arthur, J.R., Boyne, R., Superoxide dismulase and glutathione peroxidase activities in neutrophils from selenium deficient and copper deficient cattle (1985) Life Sci, 36, pp. 1569-1575
  • Paglia, D.E., Valentine, W.N., Studies on the quantitative and qualitative characterization of erythrocyte glutation peroxidase (1967) J Lab Clin Med, 70, pp. 158-169
  • Nakanishi, H., Mizutani, Y., Kawauchi, A., Significant antitumoral activity of cationic multilamellar liposome containing human IFN-β gene against human renal cell carcinoma (2003) Clin Cancer Res, 19, pp. 1129-1135
  • (2003) Statistix 8, Tallase, , Analytical software, FL, USA
  • Videla, L.A., Sir, T., Wolff, C., Increased lipid peroxidation in hyperthyroid patients: Suppression by propylthiouracil treatment (1988) Free Radic Res Commun, 5, pp. 1-10
  • Abalovich, M., Llesuy, S., Gutierrez, S., Repetto, M., Peripheral parameters of oxidative stress in Graves' disease: The effects of methimazole and 131-iodine treatments (2003) Clin Endocrinol, 59, pp. 321-327
  • Franco, M.C., Archiuch, V.G., Peralta, J.G., Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase (2006) J Biol Chem, 281, pp. 4779-4786
  • Tapia, G., Cornejo, P., Fernandez, V., Videla, L.A., Protein oxidation in thyroid hormone-induced liver oxidative stress: Relation to lipid peroxidation (1999) Toxicol Lett, 106, pp. 209-214
  • Bevenga, S., Robbins, J., Thyroid hormone efflux from monolayer cultures of human fibroblasts and hepatocytes. Effect of lipoprotein and other thyroxine transport proteins (1998) Endocrinology, 139, pp. 4311-4318
  • Miler, E., Burdman, J.A., Rios de Molina, M.C., Bechara, Y., Guerra, L.N., Thyroid hormone and oxidative metabolism Free Radical Research International 2004, pp. 329-333. , Puntarulo S, Boveris A, eds
  • Pamplona, R., Portero-Otin, M., Ruiz, C., Thyroid status modulates glycoxidative and lipoxidative modification of tissue proteins (1999) Free Radic Biol Med, 27, pp. 901-910
  • Fernandez, V., Castillo, I., Tapia, G., Thyroid hormone preconditioning: Protection against ischemia-reperfusion liver injury in the rat (2007) Hepatology, 45, pp. 170-177
  • Actis-Goretta, L., Carrasquedo, F., Fraga, C.G., The regular supplementation with an antioxidant mixture decreases oxidative stress in healthy humans. Gender effect (2004) Clin Chim Acta, 349, pp. 97-103
  • Guaiquil, V.H., Golde, D.W., Beckles, D.L., Mascareno, E.J., Siddiqui, M.A., Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathway in cardiomyocytes and ischemic hearts (2004) Free Radic Biol Med, 37, pp. 1419-1429
  • Nair, V.D., Yuen, T., Olanow, C.W., Sealfon, S.C., Early single cell bifurcation of pro-and anti-apoptotic states during oxidative stress (2004) J Biol Chem, 262, pp. 27494-27501
  • Fernandez, V., Reyes, S., Bravo, S., Involvement of Kupffer cell-dependent signalling in T3-induced hepatocyte proliferation in vivo (2007) Biol Chem, 388, pp. 831-837
  • Ledda-Columbano, G.M., Perra, A., Loi, R., Shinozuka, H., Columbano, A., Cell proliferation induced by triiodothyronine in rat liver is associated with nodule regression and reduction of hepatocellular carcinomas (2000) Cancer Res, 60, pp. 603-609
  • Mihara, S., Suzuki, N., Wakisaka, S., Effects of thyroid hormones on apoptotic cell death of human lymphocytes (1999) J Clin Endocrinol Metab, 84, pp. 1378-1385


---------- APA ----------
Miler, E.A., Ríos de Molina, M. del C., Domínguez, G. & Guerra, L.N. (2008) . Thyroid hormone effect in human hepatocytes. Redox Report, 13(4), 185-191.
---------- CHICAGO ----------
Miler, E.A., Ríos de Molina, M. del C., Domínguez, G., Guerra, L.N. "Thyroid hormone effect in human hepatocytes" . Redox Report 13, no. 4 (2008) : 185-191.
---------- MLA ----------
Miler, E.A., Ríos de Molina, M. del C., Domínguez, G., Guerra, L.N. "Thyroid hormone effect in human hepatocytes" . Redox Report, vol. 13, no. 4, 2008, pp. 185-191.
---------- VANCOUVER ----------
Miler, E.A., Ríos de Molina, M. del C., Domínguez, G., Guerra, L.N. Thyroid hormone effect in human hepatocytes. Redox Rep. 2008;13(4):185-191.