Curcumin exerts protective effects on the thyroid gland in propylthiouracil-treated rats
Abstract
Introduction. Among the plant ingredients, some compounds interfere with the functions of the thyroid gland. However, there is limited research on the effect of curcumin (CMN) on the functions of this gland. The aim of this study was to analyze the effect of CMN on morphology, histochemical reactivity of cytochrome c oxidase (CCO) and secretion functions of the thyroid gland under conditions of hypothyroidism induced by propylthiouracil (PTU). Material and methods. The rats were treated for 30 days by gavage with CMN (100 mg/kg b.w.) and/or PTU (1 mg/kg b.w.). Control rats received vehicle only. Histomorphometric tests were performed on the thyroid glands, cytochrome c oxidase activity was visualized using the histochemical method, and the levels of thyroid hormones were measured using the radioimmunoassay method. Results. Rats receiving PTU showed compensatory changes in their thyroid glands, including a significant increase in thyroid epithelium height, a decrease in colloid volumen density, a decrease in the percentage of small follicles, an increase in medium-sized follicles compared to the control group, as well as a significant increase in CCO histochemical reactivity in the columnar epithelium and a decrease in FT4 serum level compared to the control group. The administration of CMN reversed these adverse changes caused by PTU. The PTU + CMN group exhibited a significant decrease in the height of the thyroid follicle epithelium compared to the PTU group. The percentage of small and medium-size follicles in the CMN + PTU group did not differ from the control group. Furthermore, CCO reactivity in the cubic epithelium and serum FT4 levels increased compared to the PTU group. Administration of CMN alone resulted in a significant increase in FT4 levels compared to the control group. Conclusions. The administration of CMN to rats with induced hypothyroidism resulted in a reduction of hyperplasia, hypertrophy, and increase in secretory activity of the thyroid gland. These findings suggest the protective effect of CMN against induced hypothyroidism.
Keywords: ratthyroidpropylthiouracilcurcuminhistomorphometrycytochrome c oxidasehistochemistry
References
- Nelson KM, Dahlin JL, Bisson J, et al. The essential medicinal chemistry of curcumin. J Med Chem. 2017; 60(5): 1620–1637.
- Papież MA. The influence of curcumin and (-)-epicatechin on the genotoxicity and myelosuppression induced by etoposide in bone marrow cells of male rats. Drug Chem Toxicol. 2013; 36(1): 93–101.
- Fuloria S, Mehta J, Chandel A, et al. A comprehensive review on the therapeutic potential of linn. in relation to its major active constituent curcumin. Front Pharmacol. 2022; 13: 820806.
- National Toxicology Program. NTP Toxicology and Carcinogenesis Studies of Turmeric Oleoresin (CAS No. 8024-37-1) (Major Component 79%-85% Curcumin, CAS No. 458-37-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). Natl Toxicol Program Tech Rep Ser. 1993; 427: 1–275.
- Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002; 110 Suppl 3(Suppl 3): 349–353.
- de Carvalho DP, Rego KG, Rosenthal D. Thyroid peroxidase in dyshormonogenetic goiters with organification and thyroglobulin defects. Thyroid. 1994; 4(4): 421–426.
- Gonçalves CF, Santos MC, Ginabreda MG, et al. Flavonoid rutin increases thyroid iodide uptake in rats. PLoS One. 2013; 8(9): e73908.
- Paunkov A, Chartoumpekis DV, Ziros PG, et al. Impact of antioxidant natural compounds on the thyroid gland and implication of the keap1/nrf2 signaling pathway. Curr Pharm Des. 2019; 25(16): 1828–1846.
- Sartelet H, Serghat S, Lobstein A, et al. Flavonoids extracted from fonio millet (Digitaria exilis) reveal potent antithyroid properties. Nutrition. 1996; 12(2): 100–106.
- The Latest Research and Development of Minerals in Human Nutrition. Advances in Food and Nutrition Research. 2021.
- Loh KC. Amiodarone-induced thyroid disorders: a clinical review. Postgrad Med J. 2000; 76(893): 133–140.
- Morariu ID, Avasilcai L, Cioanca O, et al. The effects of honey sulfonamides on immunological and hematological parameters in wistar rats. Medicina (Kaunas). 2022; 58(11).
- Elshorbagy HH, Barseem NF, Suliman HA, et al. The impact of antiepileptic drugs on thyroid function in children with epilepsy: new versus old. Iran J Child Neurol. 2020; 14(1): 31–41.
- Singh S, Panda V, S S, et al. Protective effect of a polyherbal bioactive fraction in propylthiouracil-induced thyroid toxicity in ratsby modulation of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. Toxicol Rep. 2020; 7: 730–742.
- Di Dalmazi G, Giuliani C. Plant constituents and thyroid: A revision of the main phytochemicals that interfere with thyroid function. Food Chem Toxicol. 2021; 152: 112158.
- Papiez MA, Kaja M, Gebarowska A. Age-dependent different action of curcumin in thyroid of rat. Folia Histochem Cytobiol. 2008; 46(2): 205–211.
- Abdelaleem MM, El-Tahawy NF, Abozaid SM, et al. Possible protective effect of curcumin on the thyroid gland changes induced by sodium fluoride in albino rats: light and electron microscopic study. Endocr Regul. 2018; 52(2): 59–68.
- Abd El-Twab SM, Abdul-Hamid M. Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines. The Journal of Basic & Applied Zoology. 2016; 76: 7–19.
- Mishra P, Paital B, Jena S, et al. Possible activation of NRF2 by Vitamin E/Curcumin against altered thyroid hormone induced oxidative stress via NFĸB/AKT/mTOR/KEAP1 signalling in rat heart. Sci Rep. 2019; 9(1): 7408.
- Habza-Kowalska E, Kaczor AA, Bartuzi D, et al. Some dietary phenolic compounds can activate thyroid peroxidase and inhibit lipoxygenase-preliminary study in the model systems. Int J Mol Sci. 2021; 22(10).
- Asghar MY, Lassila T, Törnquist K. Calcium signaling in the thyroid: friend and foe. Cancers (Basel). 2021; 13(9).
- Grigorenko B, Polyakov I, Nemukhin A. Mechanisms of ATP to cAMP conversion catalyzed by the mammalian adenylyl cyclase: a role of magnesium coordination shells and proton wires. J Phys Chem B. 2020; 124(3): 451–460.
- Jing Li, Zhang Q. Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion. Front Endocrinol (Lausanne). 2022; 13: 992883.
- Hamidie RDR, Shibaguchi T, Yamada T, et al. Curcumin induces mitochondrial biogenesis by increasing cyclic AMP levels via phosphodiesterase 4A inhibition in skeletal muscle. Br J Nutr. 2021; 126(11): 1642–1650.
- Rouse M, Younès A, Egan JM. Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity. J Endocrinol. 2014; 223(2): 107–117.
- Yamasaki K, Tago Y, Nagai K, et al. Comparison of toxicity studies based on the draft protocol for the 'Enhanced OECD Test Guideline no. 407' and the research protocol of 'Pubertal Development and Thyroid Function in Immature Male Rats' with 6-n-propyl-2-thiouracil. Arch Toxicol. 2002; 76(9): 495–501.
- Shukla Y, Arora A, Taneja P. Antimutagenic potential of curcumin on chromosomal aberrations in Wistar rats. Mutat Res. 2002; 515(1-2): 197–202.
- Löw O. Studies on quantitative morphology. VI. Morphometry of colloid and epithelium in the thyroid gland. Exp Pathol. 1982; 22(1): 43–58.
- Zieliński KW, Strzelecki M. Komputerowa analiza obrazu biomedycznego. Wydawnictwo Naukowe PWN, Warszawa 2002.
- Pearse AGE. Histochemistry. Theoretical and Applied. Volume one: Preparative and optical technology, 4th ed. Churchill-Livingstone, London 1980.
- Paczkowska K, Otlewska A, Loska O, et al. Laboratory interference in the thyroid function test. Endokrynol Pol. 2020; 71(6): 551–560.
- Henning Y, Vole C, Begall S, et al. Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing. PLoS One. 2014; 9(11): e113698.
- Rajkovic V, Matavulj M, Johansson O. Light and electron microscopic study of the thyroid gland in rats exposed to power-frequency electromagnetic fields. J Exp Biol. 2006; 209(Pt 17): 3322–3328.
- Velický J, Titlbach M, Lojda Z, et al. Long-term action of potassium bromide on the rat thyroid gland. Acta Histochem. 1998; 100(1): 11–23.
- Oleynikov IP, Sudakov RV, Azarkina NV, et al. Direct interaction of mitochondrial cytochrome c oxidase with thyroid hormones: evidence for two binding sites. Cells. 2022; 11(5).
- Hood A, Liu YP, Gattone VH, et al. Sensitivity of thyroid gland growth to thyroid stimulating hormone (TSH) in rats treated with antithyroid drugs. Toxicol Sci. 1999; 49(2): 263–271.
- Yi X, Yamamoto K, Shu Lu, et al. Effects of propyithiouracil (PTU) administration on the synthesis and secretion of thyroglobulin in the rat thyroid gland: a quantitative immuno-electron microscopic study using immunogold technique. Endocr Pathol. 1997; 8(4): 315–325.
- Chanoine JP, Braverman LE, Farwell AP, et al. The thyroid gland is a major source of circulating T3 in the rat. J Clin Invest. 1993; 91(6): 2709–2713.
- Bruinstroop E, van der Spek A, Boelen A. Role of hepatic deiodinases in thyroid hormone homeostasis and liver metabolism, inflammation and fibrosis. Eur Thyroid J. 2023 [Epub ahead of print]; 12(3).
- Lavado-Autric R, Calvo RM, de Mena RM, et al. Deiodinase activities in thyroids and tissues of iodine-deficient female rats. Endocrinology. 2013; 154(1): 529–536.
- Bansal R, Tighe D, Danai A, et al. Polybrominated diphenyl ether (DE-71) interferes with thyroid hormone action independent of effects on circulating levels of thyroid hormone in male rats. Endocrinology. 2014; 155(10): 4104–4112.
- Nambiar PR, Palanisamy GS, Okerberg C, et al. Toxicities associated with 1-month treatment with propylthiouracil (PTU) and methimazole (MMI) in male rats. Toxicol Pathol. 2014; 42(6): 970–983.
- Silva-Gaona OG, Hernández-Ortiz M, Vargas-Ortiz K, et al. Curcumin prevents proteins expression changes of oxidative phosphorylation, cellular stress response, and lipid metabolism proteins in liver of mice fed a high-fructose diet. J Proteomics. 2022; 263: 104595.
- Lima T, Li TY, Mottis A, et al. Pleiotropic effects of mitochondria in aging. Nat Aging. 2022; 2(3): 199–213.
- Carvalho DP, Dupuy C. Thyroid hormone biosynthesis and release. Mol Cell Endocrinol. 2017; 458: 6–15.
- Zhang Li, Xu S, Cheng X, et al. Curcumin enhances the membrane trafficking of the sodium iodide symporter and augments radioiodine uptake in dedifferentiated thyroid cancer cells suppression of the PI3K-AKT signaling pathway. Food Funct. 2021; 12(18): 8260–8273.
- Ruggeri R, Minuti A, Aliquo F, et al. Curcumin attenuates the pro-inflammatory response induced by hyaluronan oligosaccharides in human thyroid fibroblasts and thyrocytes. Endocrine Abstracts. 2022.
- Abd El-Twab SM, Abdul-Hamid M. Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines. The Journal of Basic & Applied Zoology. 2016; 76: 7–19.
- Dong X, Deng L, Yao S, et al. Protective effects of curcumin against thyroid hormone imbalance after gas explosion-induced traumatic brain injury via activation of the hypothalamic-pituitary-thyroid axis in male rats. Environ Sci Pollut Res Int. 2022; 29(49): 74619–74631.
- Jawa A, Jawad A, Riaz SH, et al. Turmeric use is associated with reduced goitrogenesis: Thyroid disorder prevalence in Pakistan (THYPAK) study. Indian J Endocrinol Metab. 2015; 19(3): 347–350.