Effect of Titanium Dioxide Nanoparticles on the structure of Pituitary Gland in adult Male Albino Rats

Authors

  • Hagar Wahdan Mohamed El- Azab Department of Histology, Damietta Faculty of Medicine (for Girls), Al-Azhar University, Damietta, Egypt

DOI:

https://doi.org/10.35516/jjps.v18i4.2919

Abstract

Study objectives: It was to observe the effects on pituitary gland exposed to TiO2-NPs in matured male albino rats.

Methodology: Forty-eight male albino rats were utilized. They were divided into three main groups. Group I (control) and was subdivided equally into three subgroups (negative control and vehicles controls). Group II (the treated group) subdivided into three equal subgroups. GII a: treated with TiO2 solution (10 mg/kg/day orally) for 14 days. Group IIb: treated with TiO2 solution (10 mg/kg/day) orally for 60 days. Group IIc (recovery): treated with TiO2 10 mg/kg/day for 60 days, then stopped treatment for 60 days. Group III was divided equally into two subgroups. GIII a: 6 rats treated with TiO2 solution (100 mg/kg/day) orally for 14 days. GIII b (recovery): 6 rats treated with TiO2 (100 mg/kg/day) for 14 days, then stopped treatment with TiO2 for 14 days. Pituitary gland specimens were prepared and examined by light and electron microscopy. Data of morphometric study was documented. 

Results: TiO2 treated groups showed structural disorganization in the pars distalis (enlarged basophil cells with vacuolated cytoplasm and pyknotic nuclei) associated with congested blood vessels and inflammatory cellular infiltration. A significant reduction of Periodic-Acid-Schiff reaction coupled with a substantial increase in area percentage of collagen fibres was observed upon TiO2-NPs. The ultrastructural assessment confirmed these distortions. The recovery groups showed different degrees of improvement in previous histological changes.

Conclusions: TiO2NPs cause time and dose-dependent structural changes in the pars distalis of the anterior pituitary gland with various degrees of distortions.

References

Thakur, M., Wang, B., & Verma, M. L. (2022). Development and applications of nanobiosensors for sustainable agricultural and food industries: Recent developments, challenges and perspectives. Environmental Technology & Innovation, 26, 102371, pp. 1-17.‏

Jovanović B.,& Palić D. (2012). Immunotoxicology of non-functionalized engineered nanoparticles in aquatic organisms with special emphasis on fish–review of current knowledge, gap identification, and call for further research. Aquat Toxicol 15(118–119):141–151

Martínez-Gutierrez F, Thi EP, Silverman JM, de Oliveira CC, Svensson SL, Vanden HA, Sánchez EM, Reiner NE, Gaynor EC, Pryzdial EL, Conway EM, Orrantia E, Ruiz F, Av-Gay Y, Bach H (2012) Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine, 8(3):328–336

Rajaiah, S. G., Nadoor, P., Rao, S., Poojari, R., Rajashekaraiah, R., Prasad, T. N. V. K. V., & Yegireddy, M. (2022). Comparative Studies on Dispersion Characters of Titanium Dioxide (TiO2) Nanoparticles for Rodent Toxicology Studies.‏ Applied Nano Bioscience, 12(2), 1-9.

Mohammed, E. T., & Safwat, G. M. (2020). Grape Seed Proanthocyanidin Extract Mitigates Titanium Dioxide Nanoparticle (TiO 2-NPs)–Induced Hepatotoxicity Through TLR-4/NF-κB Signaling Pathway. Biological Trace Element Research, 196(2), 579–589.

Baranowska-Wójcik, E., Szwajgier, D., Oleszczuk, P., & Winiarska-Mieczan, A. (2020). Effects of Titanium Dioxide Nanoparticles Exposure on Human Health—a Review. Biological Trace Element Research, 193(1), 118–129.

Perez-Castro, C., Renner, U., Haedo, M. R., Stalla, G. K., & Arzt, E. (2012). Cellular and molecular specificity of pituitary gland physiology. Physiological reviews 92(1), 1-38.‏

Coronel-Restrepo, N., Syro, L. V., Rotondo, F., & Kovacs, K. (2022). Anatomy of the Pituitary Gland. In Pituitary Adenomas: The European Neuroendocrine Association's Young Researcher Committee Overview, (pp. 1-19). Springer, Cham.

Vasantharaja, D., Ramalingam, V., & Reddy, G. A. (2015). toxic exposure dioxide nanoparticles on serum biochemical changes in adult male Wistar rats. Nanomedicine Journal, 2(1), 46–53.

El-Bestawy, E. M., & M Tolba, A. (2020). Effects of titanium dioxide nanoparticles on the myocardium of the adult albino rats and the protective role of β-carotene (histological, immunohistochemical and ultrastructural study). Journal of Molecular Histology, 51(5), 485-501.

Leng, W., Pati, P., & Vikesland, P. J. (2015). Room temperature seed mediated growth of gold nanoparticles: mechanistic investigations and life cycle assesment. Environmental Science: Nano, 2(5), 440–453.

Jafari, A., Karimipour, M., Khaksar, M. R., & Ghasemnejad-Berenji, M. (2020). Protective effects of orally administered thymol against titanium dioxide nanoparticle- induced testicular damage. Environmental Science and Pollution Research, 27(2), 2353-2360.‏

Abbasi-Oshaghi, E., Mirzaei, F., & Pourjafar, M. (2019). NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study. International Journal of Nanomedicine, 14, 1919.

Bancroft, J. D. &Layton, C. (2019). Fixation of tissues in Bancroft's Theory and Practice of Histological Techniques (8th Ed., pp.130–180): Elsevier health sciences.

Glauert, A. M., & Lewis, P. R. (2014). Biological specimen preparation for transmission electron microscopy. (2nd Ed. pp.77-310) Princeton University Press.‏New Jersy, U.S.A.

Wang, S., Alenius, H., El-Nezami, H., & Karisola, P. (2022). A New Look at the Effects of Engineered ZnO and TiO2 Nanoparticles: Evidence from Transcriptomics Studies. Nanomaterials, 12(8), 1247.‏

Iftikhar, M., Noureen, A., Uzair, M., Jabeen, F., Abdel Daim, M., & Cappello, T. (2021). Perspectives of Nanoparticles in Male Infertility: Evidence for Induced Abnormalities in Sperm Production. International Journal of Environmental Research and Public Health, 18(4), 1758.

Wang, Y., Chen, Z., Ba, T., Pu, J., Chen, T., Song, Y., Gu, Y., Qian, Q., Xu, Y., & Xiang, K. (2013). Susceptibility of young and adult rats to the oral toxicity of titanium dioxide nanoparticles. Small, 9(9‐10), 1742–1752.

Ranjan, S., Dasgupta, N., Verma, P., & Ramalingam, C. (2020). Acute and sub-chronic toxicity of titanium dioxide nanoparticles synthesized by microwave-irradiation-assisted hybrid chemical approach. J Indian Chem Soc, 97, 483-491.‏

El-Azab, N. E. E., & Salem, M. Y. (2015). Are titanium dioxide nanoparticles toxic to the cerebral cortex of rats? A histological and immunohistochemical study. Egyptian Journal of Histology, 38(3), 573–581.

Shah, S. N. A., Shah, Z., Hussain, M., & Khan, M. (2017). Hazardous Effects of Titanium Dioxide Nanoparticles in Ecosystem. Bioinorganic Chemistry and Applications.

Wu, T., & Tang, M. (2018). The inflammatory response to silver and titanium dioxide nanoparticles in the central nervous system. Nanomedicine, 13(2).

Abbott Chalew, T. E., & Schwab, K. J. (2013). Toxicity of commercially available engineered nanoparticles to Caco-2 and SW480 human intestinal epithelial cells. Cell Biology and Toxicology, 29(2), 101–116.

Hu, X., Li, D., Gao, Y., Mu, L., & Zhou, Q. (2016). Knowledge gaps between nanotoxicological research and nanomaterial safety. Environment International, 94,8–23.

Gunawan, C., Teoh, W. Y., Marquis, C. P., & Amal, R. (2013). Induced adaptation of Bacillus sp. to antimicrobial nanosilver. Small, 9(21), 3554–3560.

Younes, N. R. Ben, Amara, S., Mrad, I., Ben-Slama, I., Jeljeli, M., Omri, K., El Ghoul, J., El Mir, L., Rhouma, K. Ben, Abdelmelek, H., & Sakly, M. (2015). Subacute toxicity of titanium dioxide (TiO2) nanoparticles in male rats: emotional behavior and pathophysiological examination. Environmental Science and Pollution Research, 22(11), 8728–8737.

Hong, F., Si, W., Zhao, X., Wang, L., Zhou, Y., Chen, M., Ge, Y., Zhang, Q., Wang, Y., & Zhang, J. (2015). TiO2 Nanoparticle Exposure Decreases Spermatogenesis via Biochemical Dysfunctions in the Testis of Male Mice. Journal of Agricultural and Food Chemistry, 63(31), 7084–7092.

Sang, X., Zheng, L., Sun, Q., Li, N., Cui, Y., Hu, R., Gao, G., Cheng, Z., Cheng, J., Gui, S., Liu, H., Zhang, Z., & Hong, F. (2012). The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles. Journal of Biomedical Materials Research - Part A, 100 A(4), 894–902.

Müller, L., Riediker, M., Wick, P., Mohr, M., Gehr, P., & Rothen-Rutishauser, B. (2010). Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. Journal of the Royal Society Interface, 7(suppl_1), S27–S40.

Salman, A. S., Al-Shaikh, T. M., Hamza, Z. K., El-Nekeety, A. A., Bawazir, S. S., Hassan, N. S., & Abdel-Wahhab, M. A. (2021). Matlodextrin-cinnamon essential oil nanoformulation as a potent protective against titanium nanoparticles-induced oxidative stress, genotoxicity, and reproductive disturbances in male mice. Environmental Science and Pollution Research, 1–17.

Rossi, E. M., Pylkkänen, L., Koivisto, A. J., Vippola, M., Jensen, K. A., Miettinen, M., Sirola, K., Nykäsenoja, H., Karisola, P., & Stjernvall, T. (2010). Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. Toxicological Sciences, 113(2), 422–433.

Shakeel, M., Jabeen, F., Qureshi, N. A., & Fakhr-e-Alam, M. (2016). Toxic effects of titanium dioxide nanoparticles and titanium dioxide bulk salt in the liver and blood of male Sprague-Dawley rats assessed by different assays. Biological Trace Element Research, 173(2), 405–426

Hassanein, K. M. A., & El-Amir, Y. O. (2017). Protective effects of thymoquinone and avenanthramides on titanium dioxide nanoparticles induced toxicity in Sprague-Dawley rats. Pathology-Research and Practice, 213(1), 13–22.

Breitzig, M., Bhimineni, C., Lockey, R., & Kolliputi, N. (2016). 4-Hydroxy-2-nonenal: a critical target in oxidative stress? American Journal of Physiology-Cell Physiology, 311(4), C537–C543.

Salem, M. M., Altayeb, Z. M., & El-Mahalaway, A. M. (2017). Histological and immunohistochemical study of titanium dioxide nanoparticle effect on the rat renal cortex and the possible protective role of lycopene. Egyptian Journal of Histology, 40(1), 80–93.

Wright, C., Iyer, A. K. V, Wang, L., Wu, N., Yakisich, J. S., Rojanasakul, Y., & Azad, N. (2017). Effects of titanium dioxide nanoparticles on human keratinocytes. Drug and Chemical Toxicology, 40(1), 90–100.

Omar, A. I., & Kamar, S. S. (2021). Does repeated gold-nanoparticles administration affect pars distalis hormonal and folliculo-stellate cells in adult male albino rats? Folia Histochemica et Cytobiologica, 59(2), 95–107.

Chavhan, P. R., & Dhamani, A. (2016). Ultrastructural characterization of Gonadotrophs in the Wild caught female bat Taphozous nudiventris kachhensis (Dobson). Journal of Microscopy and Ultrastructure, 4(2), 108-114.‏

Abdel-Aziz, H. O., & El Haliem, N. G. (2012). Ultrastructural study of the effect of carbon tetrachloride on the pars distalis of the anterior pituitary gland of mice and the possible protective role of ginger. Egyptian Journal of Histology, 35(3), 598-606.‏

Tassinari, R., Cubadda, F., Moracci, G., Aureli, F., D’Amato, M., Valeri, M., De Berardis, B., Raggi, A., Mantovani, A., & Passeri, D. (2014). Oral, short-term exposure to titanium dioxide nanoparticles in Sprague-Dawley rat: focus on reproductive and endocrine systems and spleen. Nanotoxicology, 8(6), 654–662.

Bonora, M., Patergnani, S., Ramaccini, D., Morciano, G., Pedriali, G., Kahsay, A. E., Bouhamida, E., Giorgi, C., Wieckowski, M. R., & Pinton, P. (2020). Physiopathology of the permeability transition pore: Molecular mechanisms in human pathology. Biomolecules, 10(7), 998.

Shukla, R. K., Kumar, A., Vallabani, N. V. S., Pandey, A. K., & Dhawan, A. (2014). Titanium dioxide nanoparticle-induced oxidative stress triggers D.N.A. damage and hepatic injury in mice. Nanomedicine, 9(9), 1423–1434.

Siddiqi NJ, Abdelhalim MA, El-Ansary AK, et al. (2012) Identification of potential biomarkers of gold nanoparticle toxicity in rat brains. J Neuroinflammation. 9: 123

Manke, A., Wang, L., & Rojanasakul, Y. (2013). Mechanisms of nanoparticle-induced oxidative stress and toxicity. BioMed research international, 2013.‏

Reiter, R. J., Tan, D. X., Kim, S. J., Manchester, L. C., Qi, W., Garcia, J. J., ... & Rouvier-Garay, V. (1999). Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mechanisms of Ageing and Development, 110(3), 157-173.‏

Salem, R. R., & Kelada, M. N. (2020). A Biochemichal and Ultrastructural Study on the Effect of Toluene on the Pars Distalis of Anterior Pituitary Glands of Adult Male Albino Rats. Egyptian Journal of Histology, 43(3), 948–959.

Luabi, N. M., Zayed, N. A., & Ali, L. Q. (2019). Zinc oxide nanoparticles effect on thyroid and testosterone hormones in male rats. In Journal of Physics: Conference Series (Vol. 1294, No. 6, p. 062034). I.O.P. Publishing.‏

Heo, M. B., Kwak, M., An, K. S., Kim, H. J., Ryu, H. Y., Lee, S. M., Song, K. S., Kim, I. Y., Kwon, J.-H., & Lee, T. G. (2020). Oral toxicity of titanium dioxide P25 at repeated dose 28-day and 90-day in rats. Particle and Fibre Toxicology, 17(1), 1–22.

Jia, X., Wang, S., Zhou, L., & Sun, L. (2017). The potential liver, brain, and embryo toxicity of titanium dioxide nanoparticles on mice. Nanoscale Research Letters, 12(1), 1–14.

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Published

2025-12-18

How to Cite

El- Azab, H. W. M. (2025). Effect of Titanium Dioxide Nanoparticles on the structure of Pituitary Gland in adult Male Albino Rats . Jordan Journal of Pharmaceutical Sciences, 18(4), 907–923. https://doi.org/10.35516/jjps.v18i4.2919

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