Histopathological Effects of Oral Iron Sulfate, Iron Oxide, and Nano Iron Oxide in Rats
DOI:
https://doi.org/10.64614/vzs-28Keywords:
Histopathology, iron compounds, oral exposure, ratsAbstract
The present study aimed to compare the histopathological effects of nano iron oxide, conventional iron oxide, and iron sulfate following oral exposure in rats. Groups of five rats each received either vehicle, nano iron oxide, iron oxide, or iron sulfate (25.00 mg/kg, orally, once daily) for 28 days. Stomach, liver, and spleen tissues were processed for hematoxylin and eosin staining and examined under light microscopy for qualitative and morphometric evaluation. In the stomach, iron sulfate treatment increased the number of zymogen cells by 53% and undifferentiated cells by 100% (P < 0.05). The length of gastric glands was elevated by 60% and 46% in the iron sulfate and iron oxide groups, respectively (P < 0.05), while nano iron oxide had no significant effect. Interestingly, in the liver necrotic cells decreased by 85%, 71%, and 78% in the iron sulfate, iron oxide, and nano iron oxide groups, respectively (P < 0.05). In the spleen, only iron oxide induced a 93% increase in hemosiderin-containing cells (P < 0.05). These results suggest that iron sulfate may promote gastric cell proliferation and differentiation, while all three iron compounds appear to reduce cellular necrosis. However, conventional iron oxide may pose a risk of hemosiderosis.
References
Askri, D., Ouni, S., Galai, S., Chovelon, B., Arnaud, J., Sturm, N., Lehmann, S.G., Sakly, M., Amara, S., & Sève, M. (2019). Nanoparticles in foods? A multiscale physiopathological investigation of iron oxide nanoparticle effects on rats after an acute oral exposure: Trace element biodistribution and cognitive capacities. Food and Chemical Toxicology, 127, 173-181.
DOI: https://doi.org/10.1016/j.fct.2019.03.006 DOI: https://doi.org/10.1016/j.fct.2019.03.006
Babadi, V.Y., Najafi, L., Najafi, A., Gholami, H., Zarji, M.E.B., Golzadeh, J., Amraie, E., & Shirband, A. (2012). Evaluation of iron oxide nanoparticles effects on tissue and enzymes of liver in rats. Journal of Pharmaceutical and Biomedical Sciences, 23(23), 1-4.
Benoni, G., Cuzzolin, L., Zambreri, D., Donini, M., Del Soldato, P., & Caramazza, I. (1993). Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats. Pharmacological Research, 27(1), 73-80.
DOI: https://doi.org/10.1006/phrs.1993.1007 DOI: https://doi.org/10.1006/phrs.1993.1007
Berry, C.C., Wells, S., Charles, S., & Curtis, A.S. (2003). Dextran and albumin derivatised iron oxide nanoparticles: Influence on fibroblasts in vitro. Biomaterials, 24(25), 4551-4557.
DOI: https://doi.org/10.1016/S0142-9612(03)00237-0 DOI: https://doi.org/10.1016/S0142-9612(03)00237-0
Berry, C.C., Wells, S., Charles, S., Aitchison, G., & Curtis, A.S. (2004). Cell response to dextran derivatised iron oxide nanoparticles post internalisation. Biomaterials, 25(23), 5405-5413.
DOI: https://doi.org/10.1016/j.biomaterials.2003.12.046 DOI: https://doi.org/10.1016/j.biomaterials.2003.12.046
Bonkovsky, H.L. (1991). Iron and the liver. The American Journal of the Medical Sciences, 301(1), 32-43.
DOI: https://doi.org/10.1097/00000441-199101000-00006 DOI: https://doi.org/10.1097/00000441-199101000-00006
Donaldson, K., Stone, V., Tran, C.L., Kreyling, W., & Borm, P.J. (2004). Nanotoxicology. Occupational and Environmental Medicine, 61(9), 727-728.
DOI: https://doi.org/10.1136/oem.2004.013243 DOI: https://doi.org/10.1136/oem.2004.013243
Elshemy, M.A. (2018). Iron oxide nanoparticles versus ferrous sulfate in treatment of iron deficiency anemia in rats. Egyptian Journal of Veterinary Sciences, 49(2), 103-109.
DOI: https://doi.org/10.21608/ejvs.2018.3855.1039 DOI: https://doi.org/10.21608/ejvs.2018.3855.1039
Fox, J. G. (2015). Laboratory animal medicine. Academic Press, London, UK.
DOI: https://doi.org/10.1016/B978-0-12-409527-4.00001-8 DOI: https://doi.org/10.1016/B978-0-12-409527-4.00001-8
Gualdi, R., Casalgrandi, G., Montosi, G., Ventura, E., & Pietrangelo, A. (1994). Excess iron into
hepatocytes is required for activation of collagen type I gene during experimental siderosis. Gastroenterology, 107(4), 1118-1124.
DOI: https://doi.org/10.1016/0016-5085(94)90237-2 DOI: https://doi.org/10.1016/0016-5085(94)90237-2
Gupta, R.C. (Ed.). (2012). Veterinary toxicology: Basic and clinical principles. Academic Press, London, UK.
Hoet, P.H., Brüske-Hohlfeld, I., & Salata, O.V. (2004). Nanoparticles–known and unknown health risks. Journal of Nanobiotechnology, 2(1), 12.
DOI: https://doi.org/10.1186/1477-3155-2-12 DOI: https://doi.org/10.1186/1477-3155-2-12
Kulkarni, S., Mohanty, N., Kadam, N.N., Swain, N., & Thakur, M. (2020). Green synthesis to develop iron-nano formulations and its toxicity assays. Journal of Pharmacopuncture, 23(3), 165.
DOI: https://doi.org/10.3831/KPI.2020.23.3.165 DOI: https://doi.org/10.3831/KPI.2020.23.3.165
Kumari, M., Rajak, S., Singh, S.P., Kumari, S.I., Kumar, P U., Murty, U.S.N., Mahboob, M., Grover, P., & Rahman, M.F. (2012). Repeated oral dose toxicity of iron oxide nanoparticles: Biochemical and histopathological alterations in different tissues of rats. Journal of Nanoscience and Nanotechnology, 12(3), 2149–2159.
DOI: https://doi.org/10.1166/jnn.2012.5796 DOI: https://doi.org/10.1166/jnn.2012.5796
Mahan, L.K. (2016). Krause's Food & the Nutrition Care Process-E-Book. Elsevier Health
Sciences, St. Louis, MO, USA.
Malhotra, N., Lee, J.S., Liman, R.A.D., Ruallo, J.M.S., Villaflores, O.B., Ger, T.R., & Hsiao, C.D. (2020). Potential toxicity of iron oxide magnetic nanoparticles: a review. Molecules, 25(14), 3159.
DOI: https://doi.org/10.3390/molecules25143159 DOI: https://doi.org/10.3390/molecules25143159
McGee, J.O.D., Isaacson, P.G., Wright, N.A., & Ross, D.W. (1994). Oxford textbook of pathology. Archives of Pathology and Laboratory Medicine, 118(2), 201.
Mohapatra M. (2010) Synthesis and applications of nano-structured iron oxides/hydroxides - A review. International Journal of Engineering Science and Technology, 2 (8).
DOI: https://doi.org/10.4314/ijest.v2i8.63846 DOI: https://doi.org/10.4314/ijest.v2i8.63846
Özgüner, M., & Sayın, N. (2002). Histological changes in rat liver after chronic iron-sorbitol overload. Journal of Ankara Medical School, 24, 49-54.
Reimer, P., & Weissleder, R. (1996). Development and experimental application of receptor specific MR contrast media. Der Radiologe, 36(2), 153-163. DOI: https://doi.org/10.1007/s001170050053
DOI: https://doi.org/10.1007/s00117-012-2429-6 DOI: https://doi.org/10.1007/s00117-012-2429-6
Weissleder, R., Bogdanov, A., Neuwelt, E.A., & Papisov, M. (1995). Long-circulating iron oxides for MR imaging. Advanced Drug Delivery Reviews, 16(2-3), 321-334.
DOI: https://doi.org/10.1016/0169-409X(95)00033-4 DOI: https://doi.org/10.1016/0169-409X(95)00033-4
Willems, G., Galand, P., Vansteenkiste, Y., & Zeitoun, P. (1972). Cell population kinetics of zymogen and parietal cells in the stomach of mice. Zeitschrift für Zellforschung und Mikroskopische Anatomie, 134(4), 505-518.
DOI: https://doi.org/10.1007/BF00307670 DOI: https://doi.org/10.1007/BF00307670
Zehnder, J., Katzung, S.M., & Trevor, A. (2009). Basic and clinical pharmacology. McGraw-Hill Medical, New York, USA.
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Copyright (c) 2026 Hadiseh Nouri, Goudarz Sadeghi Hashjin, Rahim Hobbenaghi, Mohammad Kazem Koohi, Zakiyeh Khorrami, Noushin Khezli, Reyhaneh Kheiry, Gholamreza Shams
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