Abstract
Thyroid hormones play a fundamental role in the regulation of metabolism of almost all mammalian tissue including the reproductive system. Hyperthyroidism in early life may cause delayed sexual maturation, although physical development is normal and skeletal growth may be accelerated. Hyperthyroidism after puberty influences reproductive functions and increases testosterone level. The aim of this work is to study the effect of induced hyperthyroidism by L-thyroxine sodium administration on the testis of rats and to evaluate the ameliorating role of different antioxidants as ascorbic acid and folic acid on the hyperthyroid state via the assessment of different biochemical markers, histopathological and immunochemical sections. DNA analysis of the D1 deiodinase was performed to determine genetic mutation due to hyperthyroidism. The results showed partially disrupted in the measured biochemical parameters and spermatogenesis in hyperthyroid rats. Post-administration of both folic and ascorbic acids together in hyperthyroid rats showed the best ameliorating effects on the thyroid hormones, testosterone, testicular GGT and ALP, and all oxidative stress markers. There is no genetic mutations that occurred in D1 deiodinase due to hyperthyroidism. These findings were indicated by the proliferating cell nuclear antigen (PCNA) studies of testes.
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Abbreviations
- ALP:
-
Alkaline phosphatase
- ABC:
-
Avidin-biotin-peroxidase
- GGT:
-
Gamma-glutamyltransferase
- GSH:
-
Reduced glutathione
- MDA:
-
Malondialdehyde
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthetase
- PCNA:
-
Proliferating cell nuclear antigen
References
Ai J, Zarifkar A, Takhshid M (2007) The effect of thyroid activity on adult ratspermatogenesis. Iran J Vet Res (Univ Shiraz) 8:155–160
Arikan E et al (2001) The Effects of Hyperthyroidism on Lipid Peroxidation, Erythrocyte Glutathione and Glutathione Peroxidase. Turk J Endocrinol Metab 1:17–19
Assaei R et al (2014) Hepatoprotective effect of saturejakhuzestanica essentialoil and vitamine in experimental hyperthyroid rats: evidence for role ofantioxidant effect. Iran J Med Sci 39:459–466
Belfield A, Goldberg DM (1971) Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme 12:561–573
Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–890
Beyer R (1983) A rapid Biuret assay for protein of fatty tissues. Anal Biochem 129:483–485
Bianchi G et al (1999) Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: effect of treatment. Horm Metab Res 31:620–624
Bozhko AP, Gorodetskaia IV, Solodkov AP (1990) Restriction of stress-induced activation of lipid peroxidation by small doses of thyroid hormones. Biull Eksp Biol Med 109:539–541
Caminos JE et al (2002) Influence of thyroidstatus and growth hormone deficiency on ghrelin. Eur J Endocrinol 147:159–163
Campos-Barros A et al (1996) Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system. J Clin Endocrinol Metab 81:2179–2185
Choksi NY et al (2003) Role of thyroid hormones in humanand laboratory animal reproductive health. Birth Defects Res B 68:479–491
Cooke PS et al (1991) Increased sperm production in adult rats after transient neonatal hypothyroidism. Endocrinology 129(1):244–148
Dumitriu L, Bartoc R, Ursu H (1988) Significance of high levels of serum malonyldialdehyde (MDA) and ceruloplasmin (CP) in hyper- and hypothyroidism. Endocrinologie 26:35–38
Faure M, Videla LALEA (1991) Evaluation of the antioxidant properties of thyroid hormones and propylthiouracil in the brain-homogenate autoxidation system and in the free radical-mediated oxidation of erythrocyte membranes. Chem Biol Interact 77:173–185
Faure P et al (2004) Thyroid hormone (T3) and its acetic derivative (TA3) protect low-density lipoproteins from oxidation by different mechanisms. Biochimie 86:411–418
Francavilla S et al (1991) Effect of thyroid hormone on the pre- and post-natal development of the rat testis. J Endocrinol 129(1):35–42
Gordon GG et al (1969) Effect of Hyperthyroidism and hypothyroidism on the metabolism of testosterone and androstenedione in man. J Clin Endocrinol Metab 29:164–1670
Iangolenko VV, Okorokov AN (1991) Blood levels of medium molecular weight peptides and lipid peroxidation activity in the differential diagnosis of diffuse toxic goiter. Probl Endokrinol (Mosk) 37:10–12
Ibrahim W, Tousson E, Ali EM (2011) Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats. Gen Gen Comp Endocrinol 174(2):143–149
Jansen HT, Iwamoto GA et al (2007) Impact of neonatal hypothyroidism on reproduction in the male hamster, Mesocricetusauratus. Physiol Behav 90:771–781
Kim SM et al (2012) Antioxidant and Protective Effects of Bupleurumfalcatum on the L-Thyroxine-Induced Hyperthyroidism in Rats. Evid Based Complement Alternat Med. doi:10.1155/2012/578497
Kittisupamongkol W (2009) Hyperthyroidism or thyrotoxicosis? Cleve Clin J Med 76:152
Kuroki Y et al (1999) Spermatogenic ability is different among males in different Ychromosome lineage. J Hum Genet 44:289–292
Lampka M et al (2006) Oxidative stress markers during a course of hyperthyroidism. Endokrynol Pol 57:218–222
Landex NL, Thomsen J, Kayser L (2006) Methimazole increases H2O2 toxicity in human thyroid epithelial cells. Acta Histochem 108:431–439
Lin HY et al (2009) L-thyroxine vs. 3,5,3′-triiodo-L-thyronine and cell proliferation: Activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Am J Physiol Cell Biol 296:980–991
Maes M et al (1997) Components of biological variation, including seasonality, in bloodconcentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthyvolunteers. ClinEndocrinol (Oxf) 46:587–598
Maia AL et al (2011) Deiodinases: the balance of thyroidhormone: type 1 iodothyroninedeiodinase in human physiology and disease. JEndocrinol 209:283–297
Mandel SJ, Brent GA, Larsen PR (1993) Levothyroxine therapy in patients with thyroiddisease. Ann Intern Med 119(6):492–502
Marinò M et al (2014) An update on the medicaltreatment of Graves' hyperthyroidism. J Endocrinol Invest 37:1041–1048
Matte C et al (2007) Concurrent folate treatment prevents Na+, K+-ATPase activity inhibition and memory impairments caused by chronic hyperhomocysteinemia during rat development. Int J Dev Neurosci 25:545–552
Melmed S, et al. (2011) Williams Textbook of endocrinology 12th ED. ISBN: 978-1-4377-0324-5 pp. 327-470.
Mesbah L et al (2004) Protective effect of flavonoides against thetoxicity of vinblastine cyclophosphamide and paracetamol by inhibition of lipidperoxidation and increase of liver glutathione. Haema 7:59–67
Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method forsimultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71
Mogulkoc R et al (2006) Effects of hyperthyroidism induced by L-thyroxin administration on lipid peroxidation in various rat tissues. Acta Biol Hung 57:157–163
Moncayo R et al (2008) The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma. BMC Endocr Disord 8:2
Morais RD et al (2013) Thyroid hormone stimulates the proliferation of Sertoli cells and single type Aspermatogonia in adult zebrafish (Daniorerio) testis. Endocrinology 154:4365–4376
Noronha JM, Sreenivasan A (1959) Formate metabolism in the vitamin B12-deficient rat. Biochem J 73:732–735
Panicker V et al (2008) A Common Variation in Deiodinase 1 Gene DIO1 Is Associated with the Relative Levels of Free Thyroxine and Triiodothyronine. J Clin Endocrinol Metab 93(8):3075–3081
Petrova S, Mikhaĭlova A, Donchev N (1992) The effect of elevated amounts of ascorbic acidon the status of the vitamin and lung disorders in guinea pigs inhaling styrene. Probl Khig 17:137–145
Quesada A et al (2002) Nitric oxide synthase activity in hyperthyroid and hypothyroid rats. Eur J Endocrinol 147:117–122
Saggu S et al (2014) Ameliorating effect of chicory (Chichoriumintybus L) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food Chem Toxicol 72:138–146
Schneider MJ et al (2013) Targeted Disruption of the Type 1 Selenodeiodinase Gene (Dio1) Results in Marked Changes in Thyroid Hormone Economy in Mice. Endocrinology 147(1):580–589
Seven A, Seymen O, Hatemi S (1996) Lipid peroxidation and vitamin E supplementation in experimental hyperthyroidism. Clin Chem 42:1118–1119
Shaw LM et al (1983) International Federation of Clinical Chemistry, (IFCC), Scientific Committee, Analytical Section. IFCC methods for the measurement of catalytic concentration of enzymes. Part 4. IFCC method for gamma-lutamyl-transferase [(gamma-glutamyl)-peptide: amino acidgamma-glutamyltransferase, EC 2.3.2.2]. J Clin Chem Clin Biochem 21:633–646
Shibutani M et al (2009) Assessment of developmental effects of hypothyroidism in rats fromin uteroand lactation exposure to anti-thyroid agents. Reprod Toxicol 28:297–307
Song Y et al (2007) Roles of hydrogen peroxide in thyroid physiology and disease. J Clin Endocrinol Metab 92:3764–3773
Suitor CW, Bailey LB (2000) Dietary folate equivalents: interpretation and application. J Am Diet Assoc 100:88–94
Tarulli GA et al (2006) Adult sertoli cells are not terminally differentiated in the Djungarian hamster: effect of FSH on proliferation and junction protein organization. Biol Reprod 74:798–806
Thakur C, Saikia TC, Yadav RN (1997) Total serum levels of triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) in school going children of Dibrugarhdistrict: An endemic goiterregion of Assam. Indian J Physiol Pharmacol 41:167–170
Tietz NW (1994) Clinical Guide to Laboratory Tests, 3rd edn. W.B. Saunders, Co, Philadelphia, pp 578–580
Tousson E et al (2011) Proliferating cell nuclear antigen as a molecular biomarker for spermatogenesis in ptu-induced hypothyroidism of rats. Reprod Sci 18:679–686
Van Haaster LH et al (2006) High neonatal triiodothyronine levels differentiated in the Djungarian hamster: effect of FSH on proliferation andjunction protein organization. Biol Reprod 74:798–806
Venditti P, Di Meo S (2006) Thyroid hormone-induced oxidative stress. Cell Mol Life Sci 63:414–434
Wong WY et al (2000) Male factor subfertility: possible causes and theimpact of nutritional factors. Fertil Steril 73:435–442
Woollard KJ et al (2002) Effects of oral vitamin C on monocyte: endothelial cell adhesion in healthy subjects. Biochem Biophys Res Commun 294:1161–1168
Xu JB, Yuan XF, Lang PZ (1997) Determination of catalase activity and catalase inhibitionby ultraviolet spectrotometry. Environ Chem 16:73–76
Zheng T, Ye L, Wu Z (2005) The observation of serum sexual hormone levels before andafter treatment in male hyperthyroidisms. Zhonghua Nan Ke Xue 11:936–938
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Beltagy, D.M., Mohamed, T.M., El Said, A.S. et al. Beneficial role of ascorbic and folic acids antioxidants against thyroxin-induced testicular dysfunction in hyperthyroid rats. Environ Sci Pollut Res 23, 17246–17254 (2016). https://doi.org/10.1007/s11356-016-6876-x
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DOI: https://doi.org/10.1007/s11356-016-6876-x