Curcumin-chitosan nanoparticles reverse propylthiouracil-induced hypothyroidism in male rats via a thyroid peroxidase (Tpo) gene-independent mechanism

Authors

  • ALAA SAEED ALMUSAWI Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine , University of Baghdad, Iraq Author

DOI:

https://doi.org/10.30539/gp3cgq97

Keywords:

Curcumin nanoparticles‎, propylthiouracil (PTU), hypothyroidism, thyroid hormones, lipid profile

Abstract

Background: Hypothyroidism is assumed to be associated with oxidative stress that can derange thyroid function as well as lipid metabolism. In the present study, the evaluation of possible protective effects of curcumin-chitosan nanoparticles (Cur-Cs-NPs) against propylthiouracil (PTU)-induced hypothyroidism in male Wistar rats is presented. Methodology: Forty male rats were divided into four groups: Control, PTU (50 mg/kg), Cur-Cs-NPs (100 μg/kg), and combined PTU + Cur-Cs-NPs. Treatments lasted for 28 days; serum TSH, T3, and T4 were measured by ELISA. Thyroid peroxidase (Tpo) gene expression was also determined in the thyroid tissue by PCR normalized to β-actin. Histopathological analysis of the thyroid tissue was also performed. Results: The PTU-treated rats showed significantly elevated TSH levels and lowered T3 and T4. PTU also raised cholesterol and lowered High Density Lipoprotein (HDL). PTU prominently downregulated the Tpo gene expression relative to the control. Treatment with Cur-Cs-NPs improved the hormone levels by declining TSH and increasing T3 and T4. Cur-Cs-NPs treatment improved significantly the levels of both cholesterol and HDL. Co-treatment with Cur-Cs-NPs did not fully restore this suppression to normal. Histopathological examination of the thyroid tissue of the PTU-treated rats confirmed the tissue damage, while the group receiving PTU followed by treatment with Cur-Cs-NPs showed improved thyroid tissue. Conclusions: Altogether, this study concluded that Cur-Cs-NPs showed antioxidant as well as protective effects on thyroid function and lipid profile in PTU-induced hypothyroidism but did not restore gene expression related to oxidative stress.

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References

Abd Al-Jaleel, R. A. (2012). Use of turmeric (Curcuma longa) on the performance and some physiological traits ‎on the broiler diets. The Iraqi Journal of Veterinary Medicine, 36(1), 51–57. ‎https://doi.org/10.30539/iraqijvm.v36i1.548

Abd El-Ghaffar, M. A., & Hashem, M. S. (2010). Chitosan and its amino acids condensation adducts as reactive ‎natural polymer supports for cellulase immobilization. Carbohydrate Polymers, 81(3), 507-516.‎

Abdelaleem, S. E., Al-Saadi, S. F., & Hussein, H. M. (2022). Protective effects of nano-curcumin on thyroid ‎oxidative stress and dyslipidemia in rats. Iraqi Journal of Veterinary Sciences, 36(2), 327–336.‎

Adibian, M., Hodaei, H., Nikpayam, O., Sohrab, G., Hekmatdoost, A., & Hedayati, M. (2019). The effects of ‎curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile ‎in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Phytotherapy ‎Research: PTR, 33(5), 1374–1383. https://doi.org/10.1002/ptr.6328

Al-Fahham, A.A. (2018). Development of new lsd formula when unequal observations numbers of observations ‎are unequal. Open Journal of Statistics, 8(2), 258-263. https://doi.org/10.4236/ojs.2018.82016

Ali, M. R., Bayati, S. M., Mahmood, M. B., & Mohammed, A. A. (2022). In vitro study of curcumin–calcium ‎carbonate–phosphate nanoparticles impact on goat coccidian oocysts. Iraqi Journal of Veterinary ‎Sciences, 36(3), 809–814. ‎

Al‑Shathir, N. M., Kudhaier, K. K., Mehdi, A. W. R., & Hussain, S. M. (2001). Serum glucose, cholesterol and ‎total lipids levels and tissue lipid peroxidation in alloxan‑diabetic rats treated with aqueous extract of ‎Nigella sativa seeds. Iraqi Journal of Veterinary Sciences, 14(3), 79–86.‎

Al-Watify, D. G. O. (2011). Oxidative stress in hypothyroidism. Journal of Babylon University/Pure Appl Sci, ‎‎19(2), 444-9.‎

Ameen, B. Q., & Nader, M. I. (2025). Investigating the association between vitamin D and anti-thyroid ‎peroxidase antibodies in hypothyroid Iraqi patients. Advances in Life Sciences, 12(1), 45–52. ‎https://www.als-journal.com/1218-25

Baker Jr, J. R., Arscott, P., & Johnson, J. (1994). An analysis of the structure and antigenicity of different forms of ‎human thyroid peroxidase. Thyroid, 4(2), 173-178.‎

Bancroft, J. D., & Gamble, M. (2008). Theory and practice of histological techniques (6th ed.). Churchill ‎Livingstone Elsevier.‎

Chakraborty, S., & Bhattacharyya, R. (2017). Oxidative stress markers and hypothyroidism: A brief review. ‎Current Research in Nutrition & Food Science, 5(1), 8–13.‎

Sharma, R., Mali, Y., Agrawal, Y. O., Agnihotri, V. V., & Goyal, S. N. (2025). Repurposing nano curcumin: ‎Unveiling its therapeutic potential in diabetic nephropathy. Current Drug Targets, 26(5), 298-319. ‎https://doi.org/10.2174/0113894501326054241126043554

‎ Cooper, D. S. (2005). Antithyroid drugs. New England Journal of Medicine, 352(9), 905–917. ‎https://doi.org/10.1056/NEJMra042972

Dalle-Donne, I., Rossi, R., Colombo, R., Giustarini, D., & Milzani, A. (2006). Biomarkers of oxidative damage in ‎human disease. Clinical Chemistry, 52(4), 601–623. https://doi.org/10.1373/clinchem.2005.061408

Darne, P. A., Mehta, M. R., Agawane, S. B., & Prabhune, A. A. (2016). Bioavailability studies of curcumin–‎sophorolipid nano-conjugates in the aqueous phase: Role in the synthesis of uniform gold ‎nanoparticles. RSC Advances, 6(72), 68504–68514. https://doi.org/10.1039/C6RA13469F

de Almeida Campos, L. A., Neto, A. F. S., Noronha, M. C. S., de Lima, M. F., Cavalcanti, I. M. F., & Santos-‎Magalhães, N. S. (2023). Zein nanoparticles for drug delivery: Preparation methods and biological ‎applications. International Journal of Pharmaceutics, 635, 122754. ‎https://doi.org/10.1016/j.ijpharm.2023.122754

Farzaei, M., Zobeiri, Mahdi., Parvizi, F., El-Senduny, Fardous F., Marmouzi, I., Coy-Barrera, E., Naseri, Rozita., ‎Nabavi, S., Rahimi, R., & Abdollahi, M. (2018). Curcumin in liver diseases: a systematic review of the ‎cellular mechanisms of oxidative stress and clinical perspective. Nutrients, 10(7). ‎http://doi.org/10.3390/nu10070855‎

Piantanida, E., Ippolito, S., Gallo, D., Masiello, E., Premoli, P., Cusini, C., ... & Tanda, M. L. (2020). The interplay ‎between thyroid and liver: implications for clinical practice. Journal of Endocrinological ‎Investigation, 43(7), 885-899.https://doi.org/10.1007/s40618-020-01208-6

Go, Y. M., & Jones, D. P. (2013). Thiol/disulfide redox states in signaling and sensing. Critical Reviews in ‎Biochemistry & Molecular Biology, 48(2), 173–181. https://doi.org/10.3109/10409238.2013.764840

Goozee, Kathryn., Shah, T., Sohrabi, H., Rainey-Smith, S., Brown, B., Verdile, G., & Martins, R. (2015). ‎Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s ‎disease. British Journal of Nutrition, 115, 449 – 465. http://doi.org/10.1017/S0007114515004687

Ezzat, W., Abdelbasset, W. K., Hussien, R. S., Azab, A. R., Sulieman, A., & Yousry, S. (2024). Effect of melatonin ‎on reproductive function in propylthiouracil induced hypothyroidism in adult male rats. European ‎Review for Medical & Pharmacological Sciences, 28(5). ‎

Kar, A., Panda, S., Singh, M., & Biswas, S. (2022). Regulation of PTU-induced hypothyroidism in rats by caffeic ‎acid primarily by activating thyrotropin receptors and by inhibiting oxidative stress. Phytomedicine ‎Plus, 2(3), 100298. https://doi.org/10.1016/j.phyplu.2022.100298

Hewlings, S., & Kalman, D. (2017). Curcumin: A Review of its effects on human health. Foods, 6. ‎http://doi.org/10.3390/foods6100092

Khuwaja, G., Moni, S. S., Alam, M. F., Makeen, H. A., Zafar, S., Ashafaq, M., ... & Shakeel Iqubal, S. M. (2024). ‎Curcumin nanogel and its efficacy against oxidative stress and inflammation in rat models of ischemic ‎stroke. Nanomedicine, 19(12), 1069-1085. https://doi.org/10.2217/nnm-2024-0008‎

Lopresti, A. (2018). The problem of curcumin and its bioavailability: Could its gastrointestinal influence ‎contribute to its overall health-enhancing effects?. Advances in Nutrition, 9, 41-50. ‎http://doi.org/10.1093/advances/nmx011

Maryoosh, T. M., Hassan, A. F., Ismael, S. H., Saihood, A. H., Hmood, K. S., & Al‑Shawi, N. N. (2023). Evaluation ‎of the genoprotective effect of curcumin against methotrexate in bone marrow and spleen cells in mice. ‎Iraqi Journal of Pharmaceutical Sciences, 32(3), 134–139. https://doi.org/10.31351/vol32iss3pp134-‎‎139

Hussin, M., Hamid, A. A., Mohamad, S., Saari, N., Bakar, F., & Dek, S. P. (2009). Modulation of lipid metabolism ‎by Centella asiatica in oxidative stress rats. Journal of Food Science, 74(2), H72-H78. ‎https://doi.org/10.1111/j.1750-3841.2009.01045.x

Niu, D. M., Hwang, B., Chu, Y. K., Liao, C. J., Wang, P. L., & Lin, C. Y. (2002). High prevalence of a novel ‎mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide ‎organification defect, and evidence for a founder effect. The Journal of Clinical Endocrinology & ‎Metabolism, 87(9), 4208-4212. https://doi.org/10.1210/jc.2002-020153

Rivolta, C. M., Esperante, S. A., Gruñeiro‐Papendieck, L., Chiesa, A., Moya, C. M., Domené, S., ... & Targovnik, ‎H. M. (2003). Five novel inactivating mutations in the thyroid peroxidase gene responsible for ‎congenital goiter and iodide organification defect. Human Mutation, 22(3), 259-259. ‎https://doi.org/10.1002/humu.9175

Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative CT method. Nature ‎Protocols, 3(6), 1101-1108. https://doi.org/10.1038/nprot.2008.73

Stohs, S., Chen, O., Ray, S., Ji, Jin., Bucci, L., & Preuss, H. (2020). Highly bioavailable forms of curcumin and ‎promising avenues for curcumin-based research and application: A Review. Molecules, 25(6), 1397. ‎http://doi.org/10.3390/molecules25061397

Tohamy, H. G., El Okle, O. S., Goma, A. A., Abdel-Daim, M. M., & Shukry, M. (2022). Hepatorenal protective ‎effect of nano-curcumin against nano-copper oxide-mediated toxicity in rats: Behavioral performance, ‎antioxidant, anti-inflammatory, apoptosis, and histopathology. Life Sciences, 292, 120296. ‎https://doi.org/10.1016/j.lfs.2021.120296

Williams, D. E., Le, S. N., Hoke, D. E., Chandler, P. G., Gora, M., Godlewska, M., ... & Buckle, A. M. (2020). ‎Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid ‎autoimmune disease. Endocrinology, 161(2), bqaa016. https://doi.org/10.1210/endocr/bqaa016

Wu, F., Zhou, X., Zhang, R., Pan, M., & Peng, K. L. (2012). The effects of ammonium perchlorate on thyroid ‎homeostasis and thyroid‐specific gene expression in rat. Environmental Toxicology, 27(8), 445-452. ‎https://doi.org/10.1002/tox.20655

Xu, Xiao-Yu., Meng, Xiao., Li, Sha., Gan, R.., Li, Ya., & Li, Huabin. (2018). Bioactivity, health benefits, and ‎related molecular mechanisms of curcumin: Current progress, challenges, and perspectives. Nutrients, ‎‎10(10). http://doi.org/10.3390/nu10101553

Yan, Y., Cai, H., & Yang, M. (2024). The application of nanotechnology for the diagnosis and treatment of ‎endocrine disorders: A review of current trends, toxicology and future perspective. International ‎Journal of Nanomedicine, 2024, 9921-9942. https://doi.org/10.2147/IJN.S477835

Yen, F., Wu, Tzu-hui, Tzeng, Cheng-Wei, Lin, Liang-Tzung, & Lin, Chun‐ching. (2010). Curcumin ‎nanoparticles improve the physicochemical properties of curcumin and effectively enhance its ‎antioxidant and antihepatoma activities. Journal of Agricultural & Food Chemistry, 58(12), 7376-82. ‎http://doi.org/10.1021/jf100135h

Zielińska, A., Carreiró, F., Oliveira, A. M., Neves, A., Pires, B., Venkatesh, D. N., ... & Souto, E. B. (2020). ‎Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules, ‎‎25(16), 3731. https://doi.org/10.3390/molecules25163731

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Published

2025-12-28

How to Cite

Curcumin-chitosan nanoparticles reverse propylthiouracil-induced hypothyroidism in male rats via a thyroid peroxidase (Tpo) gene-independent mechanism. (2025). Experimental and Applied Veterinary Research Journal, 1(1), 59-69. https://doi.org/10.30539/gp3cgq97