Abstract
Background
Iodine is a nonpareil constituent of thyroid hormones (THs) and a prime regulator of thyroid gland functioning. Although essential at recommended levels for the prevention of iodine deficiency disorders (IDDs), exposure to excess iodine reportedly causes hypothyroidism, hyperthyroidism, and several other emerging deleterious impacts. The objective of the present study is to explore the influence of excess iodide exposure on carbohydrate and lipid metabolism along with the histoarchitecture of certain associated organs such as the pancreas, liver, kidney, and skeletal and cardiac muscle because information on those aspects was found to be scanty.
Methods
Twelve rats were taken, six were fed with iodine through gavage at a dose of 3.5 mg potassium iodide (KI)/100-g body weight, which corresponded to 500 times of the physiological daily dosage of iodide for a period of 60 days, while the other six formed the control group.
Results
KI-treated rats presented high body weight and urinary iodine with low TH levels, suggesting a primary thyroid dysfunction. There was an increase in blood glucose, cholesterol, triglycerides, low density lipoprotein (LDL), and very low density lipoprotein (VLDL), while high density lipoprotein (HDL) levels decreased. Tissue glycogen content in the liver and skeletal muscle was decreased and was increased in the heart and kidney. Histological sections of the pancreas showed a complete disruption with hardly recognizable histoarchistructure. Treated liver sections displayed the broadened central vein with degenerated hepatocytes, while skeletal muscle sections showed dissolution of muscle fibre cells linked with loss of glycogen from these organs. Histological changes in the heart include features similar to those of a fatty heart with cardiac muscles mutilation, while that of the kidney shows an increase in glomerular tuft size and Bowman’s space expansion with general deterioration.
Conclusions
It may thus be concluded that excess iodine exposure for a long duration causes the development of a biochemical state of hypothyroidism. The developed hypothyroidism was found responsible for the hyperglycaemic and hypercholestromic status evident by high blood glucose and cholesterol levels and the depletion of glycogen at its storage sites in the liver and skeletal muscle but the extra deposition in the cardiac muscle and kidney; histomicrophotographs showed severe destruction of the pancreatic structure. All these alterations are conducive for the pathogenesis of cardiovascular and kidney diseases.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Funding from Departmental Grant BI (92), Department of Physiology, University of Calcutta, is acknowledged herein. Author Deotima Sarkar acknowledges fellowship received from INSPIRE Fellowship Scheme, Department of Science and Technology (DST), Government of India.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Horn-Ross PL, Morris JS, Lee M, West DW, Whittemore AS, McDougall IR, et al. Iodine and thyroid cancer risk among women in a multiethnic population. Cancer Epidemiol Biomarkers Prev 2001;10:979–85.Search in Google Scholar
2. Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol 2014;10:136–42.10.1038/nrendo.2013.251Search in Google Scholar PubMed PubMed Central
3. Zhao LN, Xu J, Peng XL, Tian LY, Hao LP, Yang XF, et al. Dose and time-dependent hypercholesterolemic effects of iodine excess via TRβ1-mediated down regulation of hepatic LDLr gene expression. Eur J Nutr 2010;49:257–65.10.1007/s00394-009-0081-3Search in Google Scholar PubMed
4. Chakraborty A, Mandal J, Mondal C, Sinha S, Chandra AK. Effect of excess iodine on oxidative stress markers, steroidogenic – enzyme activities, testicular morphology, and functions in adult male rats. Biol Trace Elem Res 2016;172:380–94.10.1007/s12011-015-0581-3Search in Google Scholar PubMed
5. Mahapatra D, Chandra AK. Biphasic action of iodine in excess at different doses on ovary in adult rats. J Trace Elem Med Biol 2017;31:210–20.10.1016/j.jtemb.2016.10.006Search in Google Scholar PubMed
6. Li N, Jiang Y, Shan Z, Teng W. Prolonged high iodine intake is associated with inhibition of type 2 deiodinase activity in pituitary and elevation of serum thyrotropin levels. Br J Nutr 2014;107:674–82.10.1017/S0007114511003552Search in Google Scholar PubMed
7. Sinha RA, Singh BK, Yen PM. Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism. Trends Endocrinol Metab 2014;25:538–45.10.1016/j.tem.2014.07.001Search in Google Scholar PubMed
8. Zhu X, Cheng SY. New insights into regulation of lipid metabolism by thyroid hormone. Curr Opin Endocrinol Diabetes Obes 2010;17:408.10.1097/MED.0b013e32833d6d46Search in Google Scholar PubMed PubMed Central
9. Lupachik SV, Nadol’nik LI, Netsetskaya ZV, Vinogradov VV. Effect of long-term injection of high doses of potassium iodide on iodine metabolism in rat thyroid gland. Biochem (Mosc) Suppl Ser B: Biomed Chem 2007;1:53–7.10.1134/S1990750807010088Search in Google Scholar
10. Karmarkar MG, Pandav CS, Krishnamachari KA. Principleand procedure for iodine estimation. In: A laboratory manual. New Delhi: Indian Council of Medical Research, 1986:1–14.Search in Google Scholar
11. Wang Z, Yang Y, Xiang X, Zhu Y, Men J, He M. Estimation of the normal range of blood glucose in rats. Wei sheng yan jiu 2010;39:133–7.Search in Google Scholar
12. Bhadoria P, Nagar M, Bahrioke V, Bhadoria AS. Effect of ethephon on the liver in albino rats: a histomorphometric study. Biomed J 2015;38:421.10.4103/2319-4170.155589Search in Google Scholar PubMed
13. Probyn ME, Parsonson KR, Gårdebjer EM, Ward LC, Wlodek ME, Anderson ST, et al. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months. PLoS One 2013;8:e59718.10.1371/journal.pone.0059718Search in Google Scholar PubMed PubMed Central
14. Dixit SG, Rani P, Anand A, Khatri K, Chauhan R, Bharihoke V. To study the effect of monosodium glutamate on histomorphometry of cortex of kidney in adult albino rats. Renal Failure 2014;36:266–70.10.3109/0886022X.2013.846865Search in Google Scholar PubMed
15. Nascimento CC, Padula N, Milani JG, Shimano AC, Martinez EZ, Mattiello-Sverzut AC. Histomorphometric analysis of the response of rat skeletal muscle to swimming, immobilization and rehabilitation. Braz J Med Biol Res 2008;41:818–24.10.1590/S0100-879X2008000900013Search in Google Scholar
16. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11.10.1016/j.clinbiochem.2005.08.008Search in Google Scholar PubMed
17. Bürgi H. Iodine excess. Best Pract Res Clin Endocrinol Metab 2010;24:107–15.10.1016/j.beem.2009.08.010Search in Google Scholar PubMed
18. Hashimoto K, Cohen RN, Yamada M, Markan KR, Monden T, Satoh T, et al. Cross-talk between thyroid hormone receptor and liver X receptor regulatory pathways is revealed in a thyroid hormone resistance mouse model. J Biol Chem 2006;281:295–302.10.1074/jbc.M507877200Search in Google Scholar PubMed
19. Chandra Amar K. Iodine, thiocyanate and the thyroid. Biochem Pharmacol (Los Angel) 2015;4:2167–0501.10.4172/2167-0501.1000171Search in Google Scholar
20. Vayre L, Sabourin JC, Caillou B, Ducreux M, Schlumberger M, Bidart JM. Immunohistochemical analysis of Na+/I-symporter distribution in human extra-thyroidal tissues. Eur J Endocrinol 1999;141:382–6.10.1530/eje.0.1410382Search in Google Scholar PubMed
21. Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide symporter (NIS): characterization, regulation, and medical significance. Endocr Rev 2003;24:48–77.10.1210/er.2001-0029Search in Google Scholar PubMed
22. De la Vieja A, Dohan O, Levy O, Carrasco N. Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. Physiol Rev 2000;80:1083–105.10.1152/physrev.2000.80.3.1083Search in Google Scholar PubMed
23. Hingorani M, Spitzweg C, Vassaux G, Newbold K, Melcher A, Pandha H, et al. The biology of the sodium iodide symporter and its potential for targeted gene delivery. Curr Cancer Drug Targets 2010;10:242–67.10.2174/156800910791054194Search in Google Scholar PubMed PubMed Central
24. Cann SA, van Netten JP, Glover DW. Iodide accumulation in extrathyroidal tissues. J Clin Endocrinol Metab 1999;84:821–2.10.1210/jcem.84.2.5472-4Search in Google Scholar PubMed
25. Costa A, Testori OB, Cenderelli C, Giribone G, Migliardi M. Iodine content of human tissues after administration of iodine containing drugs or contrast media. J Endocrinol Invest 1978;1:221–5.10.1007/BF03350384Search in Google Scholar
26. Chandra AK, Ghosh D, Tripathy S. Effect of maize (Zea mays) on thyroid status under conditions of varying iodine intake in rats. J Endocrinol Reprod 2009;13:17–26.Search in Google Scholar
27. Chandra AK, Mondal C, Sinha S, Chakraborty A, Pearce EN. Synergic actions of polyphenols and cyanogens of peanut seed coat (Arachis hypogaea) on cytological, biochemical and functionalchanges in thyroid. Indian J Exp Biol 2015;53:143–51.Search in Google Scholar
28. Okajima F, Ui M. Metabolism of glucose in hyper-and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C-and 3H-labelled glucose. Biochem J 1979;182:565–75.10.1042/bj1820565Search in Google Scholar
29. Dimitriadis GD, Leighton B, Parry-Billings M, West D, Newsholme EA. Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. Biochem J 1989;257:369–73.10.1042/bj2570369Search in Google Scholar
30. Gregory RB, Phillips JW, Henly DC, Berry MN. Effects of thyroid status on glucose cycling by isolated rat hepatocytes. Metabolism 1996;45:101–8.10.1016/S0026-0495(96)90206-1Search in Google Scholar
31. Lamberg BA. Glucose metabolism in thyroid disease. Acta Med Scand 1965;178:351–62.10.1111/j.0954-6820.1965.tb04279.xSearch in Google Scholar
32. Preiksaitis HG, Kunos G. Adrenoceptor-mediated activation of liver glycogen phosphorylase: effects of thyroid state. Life Sci 1979;24:35–41.10.1016/0024-3205(79)90277-7Search in Google Scholar
33. Giaccari A, Rossetti L. Predominant role of gluconeogenesis in the hepatic glycogen repletion of diabetic rats. J Clin Invest 1992;89:36.10.1172/JCI115583Search in Google Scholar
34. Chu DT, Shikama H, Khatra BS, Exton JH. Effects of altered thyroid status on beta-adrenergic actions on skeletal muscle glycogen metabolism. J Biol Chem 1985;260:9994–10000.10.1016/S0021-9258(17)39201-3Search in Google Scholar
35. Reichelt ME, Mellor KM, Curl CL, Stapleton DA, Delbridge LM. Myocardial glycophagy – a specific glycogen handling response to metabolic stress is accentuated in the female heart. J Mol Cell Cardiol 2013;65:67–75.10.1016/j.yjmcc.2013.09.014Search in Google Scholar PubMed
36. Kang J, Dai XS, Yu TB, Wen B, Yang ZW. Glycogen accumulation in renal tubules, a key morphological change in the diabetic rat kidney. Acta Diabetol 2005;42:110–6.10.1007/s00592-005-0188-9Search in Google Scholar PubMed
37. Rizos CV, Elisaf MS, Liberopoulos EN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J 2011;5:76–84.10.2174/1874192401105010076Search in Google Scholar
38. Zhao J, Wang P, Shang L, Sullivan KM, van der Haar F, Maberly G. Endemic goiter associated with high iodine intake. Am J Public Health 2000;90:1633–5.10.2105/AJPH.90.10.1633Search in Google Scholar
39. Han H, Xin P, Zhao L, Xu J, Xia Y, Yang X, et al. Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice. Biol Trace Elem Res 2012;147:233–9.10.1007/s12011-011-9300-xSearch in Google Scholar
40. Shin DJ, Osborne TF. Thyroid hormone regulation and cholesterol metabolism are connected through sterol regulatory element-binding protein-2 (SREBP-2). J Biol Chem 2003;278:34114–8.10.1074/jbc.M305417200Search in Google Scholar
41. Pearce EN, Wilson PW, Yang Q, Vasan RS, Braverman LE. Thyroid function and lipid subparticle sizes in patients with short-term hypothyroidism and a population-based cohort. J Clin Endocrinol Metab 2008;93:888–94.10.1210/jc.2007-1987Search in Google Scholar
42. Al-Tonsi AA, Abdel-Gayoum AA, Saad M. The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders. Exp Mol Pathol 2004;76:182–7.10.1016/j.yexmp.2003.10.006Search in Google Scholar
43. Thompson GR, Soutar AK, Spengel FA, Jadhav A, Gavigan SJ, Myant NB. Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci 1981;78:2591–5.10.1073/pnas.78.4.2591Search in Google Scholar
44. Abrams JJ, Grundy SM. Cholesterol metabolism in hypothyroidism and hyperthyroidism in man. J Lipid Res 1981;22:323–38.10.1016/S0022-2275(20)35375-XSearch in Google Scholar
45. Dullaart RP, Hoogenberg K, Groener JE, Dikkescheo L, Erkelens DW, Doorenbos H. The activity of cholesteryl ester transfer protein is decreased in hypothyroidism: a possible contribution to alterations in high-density lipoproteins. Eur J Clin Invest 1990;20:581–7.10.1111/j.1365-2362.1990.tb01904.xSearch in Google Scholar PubMed
46. Nikkilä EA, Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest 1972;51:2103.10.1172/JCI107017Search in Google Scholar PubMed PubMed Central
47. Tanis BC, Westendorp RG, Smelt AH. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clin Endocrinol 1996;44:643–9.10.1046/j.1365-2265.1996.739560.xSearch in Google Scholar PubMed
48. Bereton MF, Iber M, Shimomura K, Zhang Q, Adriaenssens AE, Proks P, et al. Reversible changes in pancreatic islet structure and function produced by elevated blood glucose. Nat Commun 2014;5:4639.10.1038/ncomms5639Search in Google Scholar PubMed PubMed Central
49. Joanta AE, Filip A, Clichici S, Andrei S, Cluj-Napoca Romania CN. Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones. Acta Physiol Hung 2006;93:347–59.10.1556/APhysiol.93.2006.4.11Search in Google Scholar PubMed
50. Kisso B, Patel A, Redetzke R, Gerdes AM. Effect of low thyroid function on cardiac structure and function in spontaneously hypertensive heart failure rats. J Card Fail 2008;14:167–71.10.1016/j.cardfail.2007.10.018Search in Google Scholar PubMed PubMed Central
51. Basu G, Mohapatra A. Interactions between thyroid disorders and kidney disease. Indian J Endocr Metab 2012;16:204.10.4103/2230-8210.93737Search in Google Scholar PubMed PubMed Central
52. Iglesias P, Diez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol 2009;160:503–15.10.1530/EJE-08-0837Search in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
