Polychlorinated Biphenyls Affect Thyroid Function and Induce Autoimmunity in Sprague-Dawley Rats

Abstract

Polychlorinated biphenyls (PCBs) have been reported to cause a variety of toxic effects. In order to assess the thyroid function after exposure to PCBs and investigate whether PCBs induce autoimmune process in the thyroid gland, we determined the levels of serum thyroid hormones (FT3, FT4, and T4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) in Sprague-Dawley rats treated with a commercial mixture of PCBs, Aroclor 1 254 (PCBs group), or the antithyroid drug, propyl-thiouracil (PTU group). The histopathology of the thyroid was also examined. Serum FT3, FT4, and T4 concentrations were significantly reduced, while TSH values were dramatically increased in PCBs group and PTU group compared with control rats (p<0.05). TPOAb levels were significantly elevated in PCBs-treated rats (p<0.05) but not in PTU group (p>0.05). In contrast to the controls, treatment with PCBs lead to distinct histopathological changes in the thyroid gland, such as hyperplasia of the epithelia in follicles, colloid content reduction, vascularization, and lymphocytic infiltration in the perifollicular areas, whereas the major changes in the thyroid in PTU-treated rats were follicles shrinkage or collapse and colloid content reduction compatible with induced hypothyroidism. The results indicate that PCBs affect thyroid function via the induction of autoimmunity, which is a mechanism different from the effect of antithyroid drug on the thyroid gland.

Key words

polychlorinated biphenyls - thyroid hormone - thyroid-stimulating hormone - antibodies to thyroperoxidase - histopathology - rat

References

• 1 Hallgren S, Sarnerud PO. Plybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing ineractions and mechanisms for thyroid hormone effects.  Toxicology. 2002;  177 227-243
• 2 Boas M, Feldt-Rasmussen U, Skakkebaek NE, Main KM. Environmental chemicals and thyroid function.  Eur J Endocrinol. 2006;  154 599-611
• 3 Chiu A, Beaubier J, Chiu J, Chan L, Gerstenberger S. Epidemiologic studies of PCB congener profiles in North American fish consuming populations.  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2004;  22 13-36
• 4 Murugesan P, Muthusamy T, Balasubramanian K, Arunakaran J. Studies on the protective role of vitamin C and E against polychlorinated biphenyl (Aroclor 1254) – induced oxidative damage in Leydig cells.  Free Radic Res. 2005;  39 1259-1272
• 5 Hretz-Picciotto I, Charles MJ, James RA, Keller JA, Willman E, Teplin S. In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth.  Epidemiology. 2005;  16 648-656
• 6 Wang SL, Su PH, Jong SB, Guo YL, Chou WL, Päpke O. In utero exposure to dioxins and polychlorinated biphenyls and its relations to thyroid function and growth hormone in newborns.  Environ Health Perspect. 2005;  113 1645-1650
• 7 Kato Y, Ikushiro S, Haraguchi K, Yamazaki T, Ito Y, Suzuki H, Kimura R, Yamada S, Inoue T, Degawa M. A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.  Toxicol Sci. 2004;  81 309-315
• 8 Hallgren S, Sinjari T, Hakansson H, Darnerud PO. Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice.  Arch Toxicol. 2001;  75 200-208
• 9 Kilic N, Sandal S, Colakoglu N, Kutlu S, Seyran A, Yilmaz B. Endocrine disruptive effects of polychlorinated biphenyls on the thyroid gland in female rats.  Tohoku J Exp Med. 2005;  206 327-332
• 10 Hsu PC, Guo YL, Li MH. Effects of acute postnatal exposure to 3,3′,4,4′-tetrachlorobiphenyl on sperm function and hormone levels in adult rats.  Chemosphere. 2004;  54 611-618
• 11 van den Berg KJ, Zurcher C, Brouwer A. Effects of 3,4,3′,4′-tetrachlorobiphenyl on thyroid function and histology in marmoset monkeys.  Toxicol Lett. 1988;  41 77-86
• 12 Kato Y, Haraguchi K, Shibahara T, Yumoto S, Masuda Y, Kimura R. Reduction of thyroid hormone levels by methylsulfonyl metabolites of tetra- and pentachlorinated biphenyls in male Sprague-Dawley rats.  Toxicol Sci. 1999;  48 51-54
• 13 Kato Y, Ikushiro S, Takiguchi R, Haraguchi K, Koga N, Uchida S, Sakaki T, Yamada S, Kanno J, Degawa M. A Novel Mechanism for Polychlorinated Biphenyl-Induced Decrease in Serum Thyroxine Level in Rats.  Drug Metab Dispos. 2007;  35 1949-1955
• 14 Osius N, Karmaus W, Kruse H, Witten J. Exposure to polychlorinated biphenyls and levels of thyroid hormones in children.  Environ Health Perspect. 1999;  107 843-849
• 15 Sala M, Sunyer J, Herrero C, To-Figueras J, Grimalt J. Association between serum concentrations of hexachlorobenzene and polychlorobiphenyls with thyroid hormone and liver enzymes in a sample of the general population.  Occup Environ Med. 2001;  58 172-177
• 16 Zoeller RT. Environmental chemicals as thyroid hormone analogues: new studies indicate that thyroid hormone receptors are targets of industrial chemicals?.  Mol Cell Endocrinol. 2005;  242 10-15
• 17 Hood A, Hashmi R, Klaassen CD. Effects of microsomal enzyme inducers on thyroid-follicular cell proliferation, hyperplasia, and hypertrophy.  Toxicol Appl Pharmacol. 1999;  160 163-170
• 18 Hood A, Klaassen CD. Differential effects of microsomal enzyme inducers on in vitro thyroxine (T(4)) and triiodothyronine (T(3)) glucuronidation.  Toxicol Sci. 2000;  55 78-84
• 19 Weetman AP, McGregor AM. Autoimmune thyroid disease: further developments in our understanding.  Endocr Rev. 1994;  15 788-830
• 20 Macht L, Fukuma N, Leader K, Sarsero D, Pegg CA, Phillips DI, Yates P, McLachlan SM, Elson C, Rees Smith B. Severe combined immunodeficient (SCID) mice: a model for investigating human thyroid autoantibody synthesis.  Clin Exp Immunol. 1991;  84 34-42
• 21 Zaletel K, Krhin B, Gaberscek S, Hojker S. Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto's thyroiditis.  Int J Immunogenet. 2006;  33 87-91
• 22 Sandal S, Yilmaz B, Godekmerdan A, Kelestimur H, Carpenter DO. Effects of PCBs 52 and 77 on Th1/Th2 balance in mouse thymocyte cell cultures.  Immunopharmacol Immunotoxicol. 2005;  27 601-613

1 Both authors contributed equally to this article.

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