open access

Ahead of Print
Original article
Submitted: 2021-03-19
Accepted: 2021-05-06
Published online: 2021-05-17
Get Citation

Green tea extract modulates lithium-induced thyroid follicular cell damage in rats

S. M. Zaki12, G. H.A. Hussein3, G. M. Helal4, S. F. Arsanyos1, W. A. Abd Algaleel1
DOI: 10.5603/FM.a2021.0052
·
Pubmed: 34018174
Affiliations
  1. Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt
  2. Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
  3. Faculty of Medicine, Beni Suef University, Egypt
  4. Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Egypt

open access

Ahead of Print
ORIGINAL ARTICLES
Submitted: 2021-03-19
Accepted: 2021-05-06
Published online: 2021-05-17

Abstract

Background: The aim of the current work was to clarify the modulation role of green tea extract (GTE) over structural and functional affection of the thyroid gland after long term use of lithium carbonate (LC). The suggested underlying mechanisms participating in thyroid affection were researched.

Materials and methods: Twenty-four Sprague-Dawley adult albino rats were included in the work. They are divided into three groups (control, LC, and concomitant LC + GTE). The work was sustained for 8 weeks. Biochemical assays were achieved (thyroid hormone profile, IL-6). Histological, histochemical (PAS) and immunohistochemical (caspase-3, TNF-α, PCNA) evaluations were done. Oxidative/antioxidative markers (MDA / GSH, SOD) and western blot evaluation of the Bcl2 family were done.

Results: LC induced hypothyroidism (decrease T3, T4/increase TSH). The follicles were distended, others were involuted. Some follicles were disorganized, others showed detached follicular cells. Apoptotic follicular cells were proved (Bax and caspase-3 increased, Bcl2 decreased, Bax/Bcl2 ratio increased). The collagen fibers' content and proinflammatory markers (TNF-α and IL-6) increased. The proliferative nuclear activity was supported by increase expression of PCNA. Oxidative stress was established (increase MDA/decrease GSH, SOD). With the use of GTE, the thyroid hormone levels increased, while the TSH level decreased. Apoptosis is improved as Bax decreased, Bcl2 increased, and Bax/Bcl2 ratio was normal. The collagen fibers' content and proinflammatory markers (TNF-α and IL-6) decreased. The expression of PCNA and caspase-3 were comparable to the control group. The oxidative markers were improved (decrease MDA/increase GSH, SOD).

Conclusions: In conclusion, prolonged use of LC results in hypothyroidism, which is accompanied by structural thyroid damage. LC induced thyroid damage through oxidative stress that prompted sterile inflammation and apoptosis. With the use of GTE, the thyroid gland achieved its structure and function. The protecting role of GTE is through antioxidant, antifibrotic, anti-inflammatory, and antiproliferative effects.

Abstract

Background: The aim of the current work was to clarify the modulation role of green tea extract (GTE) over structural and functional affection of the thyroid gland after long term use of lithium carbonate (LC). The suggested underlying mechanisms participating in thyroid affection were researched.

Materials and methods: Twenty-four Sprague-Dawley adult albino rats were included in the work. They are divided into three groups (control, LC, and concomitant LC + GTE). The work was sustained for 8 weeks. Biochemical assays were achieved (thyroid hormone profile, IL-6). Histological, histochemical (PAS) and immunohistochemical (caspase-3, TNF-α, PCNA) evaluations were done. Oxidative/antioxidative markers (MDA / GSH, SOD) and western blot evaluation of the Bcl2 family were done.

Results: LC induced hypothyroidism (decrease T3, T4/increase TSH). The follicles were distended, others were involuted. Some follicles were disorganized, others showed detached follicular cells. Apoptotic follicular cells were proved (Bax and caspase-3 increased, Bcl2 decreased, Bax/Bcl2 ratio increased). The collagen fibers' content and proinflammatory markers (TNF-α and IL-6) increased. The proliferative nuclear activity was supported by increase expression of PCNA. Oxidative stress was established (increase MDA/decrease GSH, SOD). With the use of GTE, the thyroid hormone levels increased, while the TSH level decreased. Apoptosis is improved as Bax decreased, Bcl2 increased, and Bax/Bcl2 ratio was normal. The collagen fibers' content and proinflammatory markers (TNF-α and IL-6) decreased. The expression of PCNA and caspase-3 were comparable to the control group. The oxidative markers were improved (decrease MDA/increase GSH, SOD).

Conclusions: In conclusion, prolonged use of LC results in hypothyroidism, which is accompanied by structural thyroid damage. LC induced thyroid damage through oxidative stress that prompted sterile inflammation and apoptosis. With the use of GTE, the thyroid gland achieved its structure and function. The protecting role of GTE is through antioxidant, antifibrotic, anti-inflammatory, and antiproliferative effects.

Get Citation

Keywords

lithium carbonate; green tea extract; thyroid damage; oxidative stress; inflammation; apoptosis

About this article
Title

Green tea extract modulates lithium-induced thyroid follicular cell damage in rats

Journal

Folia Morphologica

Issue

Ahead of Print

Article type

Original article

Published online

2021-05-17

Page views

752

Article views/downloads

670

DOI

10.5603/FM.a2021.0052

Pubmed

34018174

Keywords

lithium carbonate
green tea extract
thyroid damage
oxidative stress
inflammation
apoptosis

Authors

S. M. Zaki
G. H.A. Hussein
G. M. Helal
S. F. Arsanyos
W. A. Abd Algaleel

References (54)
  1. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998; 281(5381): 1322–1326.
  2. Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003; 13(1): 3–126.
  3. Benhadi N, Fliers E, Visser TJ, et al. Pilot study on the assessment of the setpoint of the hypothalamus-pituitary-thyroid axis in healthy volunteers. Eur J Endocrinol. 2010; 162(2): 323–329.
  4. Benzie IFF, Wachtel-Galor S. Herbal Medicine. Biomolecular Clinical Aspects. 2011.
  5. Berens SC, Wolff J, Murphy DL. Lithium concentration by the thyroid. Endocrinology. 1970; 87(5): 1085–1087.
  6. Birben E, Sahiner UM, Sackesen C, et al. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012; 5(1): 9–19.
  7. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007; 297(8): 842–857.
  8. D'souza D, Subhas BG, Shetty SR, et al. Estimation of serum malondialdehyde in potentially malignant disorders and post-antioxidant treated patients: A biochemical study. Contemp Clin Dent. 2012; 3(4): 448–451.
  9. Dhouib H, Jallouli M, Draief M, et al. Oxidative damage and histopathological changes in lung of rat chronically exposed to nicotine alone or associated to ethanol. Pathol Biol (Paris). 2015; 63(6): 258–267.
  10. El-Mahalaway AM, El-Azab NEE. Impacts of resveratrol versus platelet-rich plasma for treatment of experimentally lithium-induced thyroid follicular cell toxicity in rats. A histological and immunohistochemical study. Ultrastruct Pathol. 2019; 43(1): 80–93.
  11. Focosi D, Azzarà A, Kast RE, et al. Lithium and hematology: established and proposed uses. J Leukoc Biol. 2009; 85(1): 20–28.
  12. Galati G, Lin A, Sultan AM, et al. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med. 2006; 40(4): 570–580.
  13. George J, Joshi SR. Drugs and thyroid. J Assoc Physicians India. 2007; 55: 215–223.
  14. Gordon J, Crutchfield F, Jennings A, et al. Preparation of lipid-free tissue extracts for chromatographic determination of thyroid hormones and metabolites. Arch Biochem Biophys. 1982; 216(2): 407–415.
  15. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. Williams & Wilkins, Baltimore 1984.
  16. Graham H. Green tea composition, consumption, and polyphenol chemistry. Prev Med. 1992; 21(3): 334–350.
  17. Grossmann M, Weintraub BD, Szkudlinski MW. Novel insights into the molecular mechanisms of human thyrotropin action: structural, physiological, and therapeutic implications for the glycoprotein hormone family. Endocr Rev. 1997; 18(4): 476–501.
  18. Halliwell B, Gutteridge JM. Free radicals and antioxidant protection: mechanisms and significance in toxicology and disease. Hum Toxicol. 1988; 7(1): 7–13.
  19. Hamdy MA, El-Maraghy SA, Kortam MA. Modulatory effects of curcumin and green tea extract against experimentally induced pulmonary fibrosis: a comparison with N-acetyl cysteine. J Biochem Mol Toxicol. 2012; 26(11): 461–468.
  20. Hassanin KMA, Abd El-Kawi SH, Hashem KS. The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid. Int J Nanomedicine. 2013; 8: 1713–1720.
  21. Higdon JV, Frei B. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr. 2003; 43(1): 89–143.
  22. Husain K, Somani SM. Interaction of exercise training and chronic ethanol ingestion on testicular antioxidant system in rat. J Appl Toxicol. 1998; 18(6): 421–429, doi: 10.1002/(sici)1099-1263(199811/12)18:6<421::aid-jat532>3.0.co;2-r.
  23. Kalantari H, Salimi A, Rezaie A, et al. Evaluation of sub-acute oral toxicity of lithium carbonate microemulsion (nano size) on liver and kidney of mice. Jundishapur J Nat Pharm Prod. 2015; 10(1): e22312.
  24. Kleiner J, Altshuler L, Hendrick V, et al. Lithium-Induced Subclinical Hypothyroidism. J Clin Psychiatry. 1999; 60(4): 249–255.
  25. Kumarguru BN, Natarajan M, Nagarajappa AH. The pathology of lithium induced nephropathy: a case report and review, with emphasis on the demonstration of mast cells. J Clin Diagn Res. 2013; 7(2): 374–377.
  26. Kurt A, Tumkaya L, Turut H, et al. Protective effects of infliximab on lung injury induced by methotrexate. Arch Bronconeumol. 2015; 51(11): 551–557.
  27. Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009; 23(6): 723–733.
  28. Lazarus JH, Bennie EH. Effect of lithium on thyroid function in man. Acta Endocrinol (Copenh). 1972; 70(2): 266–272.
  29. Li MJ, Yin YC, Wang J, et al. Green tea compounds in breast cancer prevention and treatment. World J Clin Oncol. 2014; 5(3): 520–528.
  30. Ma J, Zou C, Guo L, et al. Novel death defying domain in met entraps the active site of caspase-3 and blocks apoptosis in hepatocytes. Hepatology. 2014; 59(5): 2010–2021.
  31. Mackowiak P, Ginalska E, Nowak-Strojec E, et al. The Influence of Hypo- and Hyperthyreosis on Insulin Receptors and Metabolism. Arch Physiol Biochem. 1999; 107(4): 273–279.
  32. McCord JM. Human disease, free radicals, and the oxidant/antioxidant balance. Clin Bioch. 1993; 26(5): 351–357.
  33. Meister A. Glutathione, ascorbate, and cellular protection. Cancer Res. 1994; 54(7 Suppl): 1969s–1975s.
  34. Mezni A, Aoua H, Khazri O, et al. Lithium induced oxidative damage and inflammation in the rat's heart: Protective effect of grape seed and skin extract. Biomed Pharmacother. 2017; 95: 1103–1111.
  35. Misra H, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972; 247(10): 3170–3175.
  36. Nair MP, Mahajan S, Reynolds JL, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system. Clin Vaccine Immunol. 2006; 13(3): 319–328.
  37. Ohishi T, Goto S, Monira P, et al. Anti-inflammatory Action of Green Tea. Antiinflamm Antiallergy Agents Med Chem. 2016; 15(2): 74–90.
  38. Oktay K, Schenken RS, Nelson JF. Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat. Biol Reprod. 1995; 53(2): 295–301.
  39. Ossani GP, Uceda AM, Acosta JM, et al. Role of oxidative stress in lithium-induced nephropathy. Biol Trace Elem Res. 2019; 191(2): 412–418.
  40. Peluso I, Serafini M. Antioxidants from black and green tea: from dietary modulation of oxidative stress to pharmacological mechanisms. Br J Pharmacol. 2017; 174(11): 1195–1208.
  41. Ramos-Vara JA, Kiupel M, Baszler T, et al. Suggested guidelines for immunohistochemical techniques in veterinary diagnostic laboratories. J Vet Diagn Invest. 2008; 20(4): 393–413.
  42. Roychoudhury S, Agarwal A, Virk G, et al. Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod Biomed Online. 2017; 34(5): 487–498.
  43. Singer I, Rotenberg D, Puschett JB. Lithium-induced nephrogenic diabetes insipidus: in vivo and in vitro studies. J Clin Invest. 1972; 51(5): 1081–1091.
  44. Singhal K, Raj N, Gupta K, et al. Probable benefits of green tea with genetic implications. J Oral Maxillofac Pathol. 2017; 21(1): 107–114.
  45. Suvarna SK, Layton C, Bancroft JD. Bancroft's theory and practice of histological techniques. Elsevier, Oxford 2019.
  46. Thakur S, Thakur S, Chaube S, et al. Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat. Reprod Toxicol. 2003; 17(6): 683–690.
  47. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998; 281: 1312–1316.
  48. Tipple TE, Rogers LK. Methods for the determination of plasma or tissue glutathione levels. Methods Mol Biol. 2012; 889: 315–324.
  49. Toplan S, Dariyerli N, Ozdemir S, et al. Lithium-induced hypothyroidism: oxidative stress and osmotic fragility status in rats. Biol Trace Elem Res. 2013; 152(3): 373–378.
  50. Tsujimoto Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes Cells. 1998; 3(11): 697–707.
  51. Valle FC, Hayashi H, Prates JC, et al. Cellular and subcellular alterations of the thyroid gland in rats caused by lithium carbonate. Bull Assoc Anat (Nancy). 1993; 77: 39–43.
  52. Velický J, Titlbach M, Lojda Z, et al. Expression of the proliferating cell nuclear antigen (PCNA) in the rat thyroid gland after exposure to bromide. Acta Histochemica. 1997; 99(4): 391–399.
  53. Wang L, Yang G, Yuan Li, et al. Green tea catechins effectively altered hepatic fibrogenesis in rats by inhibiting ERK and Smad1/2 phosphorylation. J Agric Food Chem. 2019; 67(19): 5437–5445.
  54. Zhong W, Peng J, He H, et al. Ki-67 and PCNA expression in prostate cancer and benign prostatic hyperplasia. Clin Invest Med. 2008; 31(1): E8–EE15.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By  "Via Medica sp. z o.o." sp.k., Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl