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Research Article


Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats

Ateeqah Ghayth Alzwawy, Abdelhafidh Khazri, Ahmed Kouki, Manel Ben Ali, Chayma Ben Fayala, Mossadok Ben-attia, Ezzeddine Mahmoudi, Mohsen Sakly, Riadh Marrouchi, Haïfa Tounsi-kettiti.


Abstract
Background:
Iron is a necessary trace element in the human body. However, excessive concentration can promote the overproduction of reactive oxygen species, leading to oxidative stress and organ injury.

Aim:
This research aims to evaluate the biochemical and micromorphological changes that occur following exposure to graded doses of ferrous sulfate in a rat model.

Methods:
Treated groups (D1, D2, D3 and D4) were treated orally and daily with graded doses of ferrous sulfate [12.5 mg/kg (D1), 25 mg/kg (D2), 50 mg/kg (D3, 100 mg/kg (D4)] for 6 weeks, while the control group received only saline solution (0.9% NaCl solution at 5 ml/kg body weight) during the same period.

Results:
The different doses of ferrous sulfate administered did not produce mortality. Weekly control of glucose levels in all rats revealed a remarkable interaction effect (p = 0.02) between treatment and time, indicating that the dynamics of change over time differed among the groups. Moreover, a significant effect is detected in the time factor (p < 0.001) and in the second factor, which refers to the treatments (p < 0.001). Additionally, ferrous sulfate altered differentially the levels of oxidative stress biomarkers, including glutathione, catalase, glutathione-S-transferase, and malondialdehyde, as well as the acetylcholinesterase activity in a dose- and organ-dependent manner. Histopathological examinations revealed signs of inflammation in the liver and hyperemia in the pancreas and kidney. Prussian blue staining did not reveal significant iron deposits in all organs.

Conclusion:
Excessive iron may cause oxidative damage to vital organs and alter blood glucose levels.

Key words: Iron overload; Multiple organ toxicity; Glycemia; Oxidative stress; Histopathology.


 
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How to Cite this Article
Pubmed Style

Alzwawy AG, Khazri A, Kouki A, Ali MB, Fayala CB, Ben-attia M, Mahmoudi E, Sakly M, Marrouchi R, Tounsi-kettiti H. Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. Open Vet. J.. 2026; 16(3): 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45

Web Style

Alzwawy AG, Khazri A, Kouki A, Ali MB, Fayala CB, Ben-attia M, Mahmoudi E, Sakly M, Marrouchi R, Tounsi-kettiti H. Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. https://www.openveterinaryjournal.com/?mno=274309 [Access: March 31, 2026]. doi:10.5455/OVJ.2026.v16.i3.45

AMA (American Medical Association) Style

Alzwawy AG, Khazri A, Kouki A, Ali MB, Fayala CB, Ben-attia M, Mahmoudi E, Sakly M, Marrouchi R, Tounsi-kettiti H. Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. Open Vet. J.. 2026; 16(3): 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45


Vancouver/ICMJE Style

Alzwawy AG, Khazri A, Kouki A, Ali MB, Fayala CB, Ben-attia M, Mahmoudi E, Sakly M, Marrouchi R, Tounsi-kettiti H. Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. Open Vet. J.. (2026), [cited March 31, 2026]; 16(3): 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45


Harvard Style

Alzwawy, A. G., Khazri, . A., Kouki, . A., Ali, . M. B., Fayala, . C. B., Ben-attia, . M., Mahmoudi, . E., Sakly, . M., Marrouchi, . R. & Tounsi-kettiti, . H. (2026) Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. Open Vet. J., 16 (3), 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45


Turabian Style

Alzwawy, Ateeqah Ghayth, Abdelhafidh Khazri, Ahmed Kouki, Manel Ben Ali, Chayma Ben Fayala, Mossadok Ben-attia, Ezzeddine Mahmoudi, Mohsen Sakly, Riadh Marrouchi, and Haïfa Tounsi-kettiti. 2026. Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. Open Veterinary Journal, 16 (3), 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45


Chicago Style

Alzwawy, Ateeqah Ghayth, Abdelhafidh Khazri, Ahmed Kouki, Manel Ben Ali, Chayma Ben Fayala, Mossadok Ben-attia, Ezzeddine Mahmoudi, Mohsen Sakly, Riadh Marrouchi, and Haïfa Tounsi-kettiti. "Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats." Open Veterinary Journal 16 (2026), 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45


MLA (The Modern Language Association) Style

Alzwawy, Ateeqah Ghayth, Abdelhafidh Khazri, Ahmed Kouki, Manel Ben Ali, Chayma Ben Fayala, Mossadok Ben-attia, Ezzeddine Mahmoudi, Mohsen Sakly, Riadh Marrouchi, and Haïfa Tounsi-kettiti. "Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats." Open Veterinary Journal 16.3 (2026), 1893-1912. Print. doi:10.5455/OVJ.2026.v16.i3.45


APA (American Psychological Association) Style

Alzwawy, A. G., Khazri, . A., Kouki, . A., Ali, . M. B., Fayala, . C. B., Ben-attia, . M., Mahmoudi, . E., Sakly, . M., Marrouchi, . R. & Tounsi-kettiti, . H. (2026) Subchronic comparative assessment of graded ferrous sulfate doses on biochemical, histological, and multiorgan micromorphological changes in wistar rats. Open Veterinary Journal, 16 (3), 1893-1912. doi:10.5455/OVJ.2026.v16.i3.45


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