Skip to main content
SpringerLink
Log in

Effect of sodium levothyroxine on histomorphometry, histopathology, histochemistry, and immunohistochemistry of articular cartilage in female mice

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Sodium levothyroxine is one of the common medicines used for treatment of hypothyroidism. The aim of the present study was to assess the effect of sodium levothyroxine on the middle part of tibia plateau in knee joint and related hormones in individuals affected by hypothyroidism. Fifty female mice were randomized into five groups. The first group was considered as control; the second and third groups were received different doses of levothyroxine; the forth group was undergone hypothyroidism; and the fifth group, the animals with hypothyroidism, was received levothyroxine orally. After 8 weeks, serum samples were taken to determine TSH, T4, FT4, T3, FT3, T3RU, calcium, and phosphorus. The cartilage of tibia plateau was evaluated using hematoxylin–eosin (histomorphometry of tibia plateau), toluidine blue (proteoglycans of matrix), TUNEL (chondrocytes apoptosis), and immunohistochemistry (rate of Collagen-II). The results showed that the number of chondrocytes, cartilage thickness, proteoglycans, and Collagen-II and the rate of T3 in the third group were significantly decreased; whereas, the percentage of apoptotic chondrocytes in the third group was significantly increased compared to those of other experimental groups (P < 0.05). FT3, FT4, TSH, calcium, and phosphorus values in most groups were also significantly different (P < 0.05). Regarding widely consumption of levothyroxine in hypothyroidism and its effects on knee joint cartilage, levothyroxine at high doses should be administered with care.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Basaran K, Eseceli H, Kart A (2010) The effect of oral levothyroxine sodium on serum Zn, Fe, Ca and Mg levels during acute copper sulfate toxication in rabbits. JAVA 9(2):240–247

    Google Scholar 

  • Bianco AC, Kim BW (2006) Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest 116(10):2571–2579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bianco AC, Larsen PR (2005) Cellular and structural biology of the deiodinases. Thyroid 15(8):777–786

    Article  CAS  PubMed  Google Scholar 

  • Biondi B, Cooper DS (2010) Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid 20(2):135–146

    Article  CAS  PubMed  Google Scholar 

  • Boeloni JN, Freitas Silva J, Magalhães FC, Goes AM, Serakides R (2010) Bone site-dependent effects on femur and vertebrae of female rats with thyroid dysfunctions. Acta Ortop Bras 18(5):291–294

    Article  Google Scholar 

  • Burkhardt JE, Hill MA, Carlton WW, Kesterson JW (1990) Histologic and histochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin, a fluoroquinolone. Vet Pathol 27(3):162–170

    Article  CAS  PubMed  Google Scholar 

  • Faber J, Galløe AM (1994) Changes in bone mass during prolonged subclinical hyperthyroidism due to l-thyroxine treatment: a meta-analysis. Eur J Endocrinol 130:350–356

    Article  CAS  PubMed  Google Scholar 

  • Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP (2010) Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 95(1):186–193

    Article  CAS  PubMed  Google Scholar 

  • Goggs R, Carter SD, Schulze-Tanzil G, Shakibaei M, Mobasheri A (2003) Apoptosis and the loss of chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis. Vet J 166(2):140–158

    Article  CAS  PubMed  Google Scholar 

  • Hardingham T, Tew S, Murdoch A (2002) Tissue engineering: chondrocytes and cartilage. Arthritis Res Ther 4(supl. 3):S63–S68

    Article  Google Scholar 

  • Harvey CB, Williams GR (2002) Mechanism of thyroid hormone action. Thyroid 12(6):441–446

    Article  CAS  PubMed  Google Scholar 

  • Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, Weaver C (2000) Peak bone mass. Osteoporos Int 11(12):985–1009

    Article  CAS  PubMed  Google Scholar 

  • Hunter W (1995) The classic: of the structure and disease of articulating cartilages. Clin Orthop Relat Res 317:3–6

    Google Scholar 

  • Jonklaas J (2009) Gender and age differences in levothyroxine dose requirement. Endocr Pract 15(6):1–23

    Google Scholar 

  • Khazaeel K, Mazaheri Y, Hashemi Tabar M, Najafzadeh H, Morovvati H, Ghadrdan A (2015) Effect of enrofloxacin on histochemistry, immunohistochemistry and molecular changes in lamb articular cartilage. Acta Med Iran 53(9):555–561

    PubMed  Google Scholar 

  • Ko YJ, Kim JY, Lee J, Song HJ, Kim JY, Choi NK, Park BJ (2014) Levothyroxine dose and fracture risk according to the osteoporosis status in elderly women. J Prev Med Public Health 47(1):36–46

    Article  PubMed  PubMed Central  Google Scholar 

  • Kopp P (2001) The TSH receptor and its role in thyroid disease. Cell Mol Life Sci 58(9):1301–1322

    Article  CAS  PubMed  Google Scholar 

  • McLean RM, Podell DN (1995) Bone and joint manifestations of hypothyroidism. Semin Arthritis Rheum 24(4):282–290

    Article  CAS  PubMed  Google Scholar 

  • Newman AP (1998) Articular cartilage repair. Am J Sports Med 26(2):309–324

    Article  CAS  PubMed  Google Scholar 

  • Poomthavorn P, Mahachoklertwattana P, Ongphiphadhanakul B, Preeyasombat C, Rajatanavin R (2005) Exogenous subclinical hyperthyroidism during adolescence: effect on peak bone mass. J Pediatr Endocrinol Metab 18(5):463–469

    Article  PubMed  Google Scholar 

  • Roberts CG, Ladenson PW (2004) Hypothyroidism. Lancet 363(9411):793–803

    Article  CAS  PubMed  Google Scholar 

  • Rosenthal AK, Heinkel D, Gohr CM (2003) Thyroxine stimulates transglutaminase activity in articular chondrocytes. Osteoarthr Cartil 11(6):463–470

    Article  CAS  PubMed  Google Scholar 

  • Sakano Y, Terada N, Ueda H, Fujii Y, Hamada Y, Akamatsu N, Ohno S (2000) Histological study of articular cartilage in experimental rat knee arthritis induced by intracapsular injection of cationic polyethyleneimine. Med Electron Microsc 33(4):246–257

    Article  CAS  PubMed  Google Scholar 

  • Sheppard MC, Holder R, Franklyn AJ (2002) Levothyroxine treatment and occurrence of fracture of the hip. Arch Intern Med 162(3):338–343

    Article  CAS  PubMed  Google Scholar 

  • Simon LS (2005) Osteoporosis. Clin Geriatr Med 21(3):603–629

    Article  PubMed  Google Scholar 

  • Smeets T, Van Buul S (1986) Influence of growth hormone and thyroxin on cell kinetics in the proximal tibial growth plate of Snell dwarf mice. Cell Prolif 19(2):161–170

    Article  CAS  Google Scholar 

  • Supit EJ, Peiris AN (2002) Interpretation of laboratory thyroid function tests for the primary care physician. South Med J 95(5):481–485

    Article  PubMed  Google Scholar 

  • Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY (1996) Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab 81(12):4278–4289

    CAS  PubMed  Google Scholar 

  • Williams GR (2013) Thyroid hormone action in cartilage and bone. Eur Thyroid J 2(1):3–13

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to assistance of the Research Council for their financial support.

Author information

Authors and Affiliations

  1. Department of Anatomy, Tehran Medical Science Branch, Islamic Azad University, Khaghani St., Shariati Ave, Tehran, 19395/1495, Islamic Republic of Iran

    Simin Fazelipour

  2. Department of Pathology, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran

    Minoo Shafii

  3. Department of Pharmacology, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran

    Mahsa Hadipour Jahromi

  4. Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Zahra Tootian, Mohammad Taghi Sheibani & Hassan Morovvati

  5. Department of Physiology, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran

    Marzieh Minaei

  6. Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran

    Anahita Shahriari, Pooneh Koochaki & Safora Karimi

Authors
  1. Simin Fazelipour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Minoo Shafii
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahsa Hadipour Jahromi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zahra Tootian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Taghi Sheibani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hassan Morovvati
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marzieh Minaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anahita Shahriari
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pooneh Koochaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Safora Karimi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simin Fazelipour.

Ethics declarations

Statement of ethical approval

All procedures applied in this research were in accordance with ethical rules, and all experiments on mice in this study have been approved by Institutional Animal Care and Ethics Committee of Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran, NO IR.Iau.tmu.REC.1394.39. In addition, this article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fazelipour, S., Shafii, M., Jahromi, M.H. et al. Effect of sodium levothyroxine on histomorphometry, histopathology, histochemistry, and immunohistochemistry of articular cartilage in female mice. Comp Clin Pathol 27, 45–53 (2018). https://doi.org/10.1007/s00580-017-2550-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-017-2550-z

Keywords

Search

Navigation