Ultrastructural changes in the thyroid gland under prolonged monosodium glutamate exposure and after its withdrawal
DOI:
https://doi.org/10.26641/1997-9665.2025.3.137-142Keywords:
thyroid gland, thyrocyte, ultrastructure, monosodium glutamate, Wistar rats, electron microscopy.Abstract
Background. The thyroid gland is an endocrine organ whose hormones regulate metabolism, growth, development, thermoregulation, and the functions of the nervous, cardiovascular, and reproductive systems. Monosodium glutamate (MSG; E621) is widely used as a flavor enhancer and, although generally considered safe, prolonged or high-dose consumption may exert toxic effects on various organs, including the thyroid gland. Objective. To evaluate the ultrastructural changes in thyroid follicular cells (thyrocytes) of Wistar rats under prolonged MSG exposure and after its withdrawal in an experimental setting. Materials and methods. Male Wistar rats were divided into seven experimental groups with different durations of MSG administration (4, 8, 10, 10+2, 12, 10+4, and 14 weeks) and a control group. MSG was administered orally at a dose of 0.07 g/kg/day. Thyroid glands were fixed in OsO₄, contrasted with uranyl acetate, polymerized in epoxy resin, and ultrathin sections were prepared for examination using a PEM-100 electron microscope at magnifications of 3200–8000×. The ultrastructural features of nuclei, mitochondria, endoplasmic reticulum, Golgi apparatus, secretory granules, and microvilli were analyzed. Results. Prolonged MSG exposure caused progressive ultrastructural alterations in thyrocytes, including mitochondrial swelling, cytoplasmic vacuolization, deformation of microvilli, expansion and vacuolization of endoplasmic reticulum cisternae and Golgi apparatus, and reduction in the number of secretory granules. The severity of these changes increased with the duration of MSG exposure, reaching marked dystrophic manifestations in groups with 12–14 weeks of treatment. Following MSG withdrawal, partial restoration of cellular structure was observed; however, signs of sublethal damage persisted. Conclusions. Prolonged MSG administration induces significant ultrastructural changes in thyroid follicular cells. MSG withdrawal contributes to partial recovery, but the persistence of subcellular damage indicates potential long-term functional impairments. These findings highlight the need for further assessment of MSG safety and investigation of its long-term effects on endocrine organs.
References
- Abd Allah AL. Prophylactic effect of Spirulina versus monosodium glutamate-induced thyroid disorders in experimental rats. Egypt J Nutr Health. 2021;16(1):45-59. doi: 10.21608/ejnh.2021.194461.
- Mekkawy AM, Ahmed YH, Khalaf AAA, El-Sakhawy MA. Ameliorative effect of Nigella sativa oil and vitamin C on the thyroid gland and cerebellum of adult male albino rats exposed to monosodium glutamate (histological, immunohistochemical and biochemical studies). Tissue Cell. 2020;66:101391. doi: 10.1016/j.tice.2020.101391.
- Hamad SR. Histopathological and immunohistochemical studies on the influence of orally administered monosodium glutamate, a food additive, dependent on time in vivo. J Basic Appl Zool. 2022;83:59. doi: 10.1186/s41936-022-00322-6.
- Arafa MHF-S, Gharib AF, Asker MSE. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptor downregulation, and systemic inflammatory response in young male rats: impact on miR-155 and miR-218. Open Chem. 2024;22(1):20240101. doi: 10.1515/ chem-2024-0101.
- Banerjee A, Mukherjee S, Maji BK. Worldwide flavor enhancer monosodium glutamate combined with high-lipid diet provokes metabolic alterations and systemic anomalies: an overview. Toxicol Rep. 2021;8:938-61. doi: 10.1016/j.toxrep. 2021.04.014.
- Shosha HM, Ebaid HM, Toraih EA, Abdelrazek HMA, Elrayess RA. Effect of monosodium glutamate on fetal development and progesterone level in pregnant Wistar albino rats. Environ Sci Pollut Res Int. 2023;30(17):49779-97. doi: 10.1007/ s11356-023-27940-4.
- Hazzaa SM, El-Roghy ES, Abd Eldaim MA, Elgarawany GE. Monosodium glutamate induces cardiac toxicity via oxidative stress, fibrosis, and p53 proapoptotic protein expression in rats. Environ Sci Pollut Res Int. 2020;27(16):20014-24. doi: 10.1007/ s11356-020-08460-9.
- Moldovan OL, Rusu A, Tanase C, Vari CE. Glutamate a multifaceted molecule: endogenous neurotransmitter, controversial food additive, design compound for anti-cancer drugs. A critical appraisal. Food Chem Toxicol. 2021;153:112290. doi: 10.1016/ j.fct.2021.112290.
- Nnadozie JO, Chijioke UO, Okafor OC, Ezejindu DN, Anyaeji PS. Chronic toxicity of low-dose monosodium glutamate in albino Wistar rats. BMC Res Notes. 2019;12:593. doi: 10.1186/s13104-019-4611-7.
- Khalaf HA, Arafat EA. Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study. Int J Clin Exp Pathol. 2015;8(12):15498-510. PMID: 26884820.
- Bahrii MM, Dibrova VA, Popadynets OH, Hryshchuk MI. Methods of morphological research: a monograph. Bahrii MM, Dibrova VA, editors. Vinnytsia: Nova Knyha; 2016. 328 p. Ukrainian.
- World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310(20):2191-4. doi: 10.1001/ jama.2013.281053.
- European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Stientific Purposes. Strasburg: Council of Europe. 1986;123:52. Available from: https://rm.coe.int/ 168007a67b.
- Mekkawy AM, Khalaf AAA, Ahmed YH, El-Sakhawy MA. Ultrastructural changes in thyroid follicles of albino rats exposed to monosodium glutamate: an electron microscopy study. Micron. 2022;157:103198. doi: 10.1016/j.micron. 2022.103198.
- Hamad SR, El-Bialy KA. Reversibility of MSG-induced ultrastructural thyroid alterations in adult rats after cessation of exposure. Histol Histopathol. 2021;36(10):1111-25. doi: 10.14670/HH-18-580.
- Harapko T, Mateshuk-Vatseba L. Submicroscopic Changes of Structural Components of the Spleen Due to the Action of Monosodium Glutamate. International Academy Journal Web of Scholar. 2020;6(48). doi: 10.31435/rsglobalwos/30062020/ 7126.
- Sodomora O, Mateshuk-Vatseba L, Harapko T, Kovalyshyn V, Kolishetska M. Morphology of Carotid Sinus Wall under the Influence of Monosodium Glutamate and Following Its Withdrawal: an Experimental Study. European Journal of Anatomy. 2023;27(4):401-15.
- Harapko T. Electron microscopic changes of lymph nodes during correction of sodium glutamate action by melatonin. Rep. of Morph. 2020;26(1):59-64.
- Vashcheniuk M, Mateshuk-Vatseba L. Ultrastructural changes of hypothalamic nuclei under long-term influence of monosodium glutamate and its absence. Morphologia. 2024;18(3):26–33. Ukrainian. doi: 10.26641/1997-9665.2024.3.26-33.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world.
The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.
