Protective and Therapeutic Effects of Libyan Sidr Honey on Aspartame-Induced Nephrotoxicity in Adult Albino Rats A Histopathological Study

Authors

  • Nadia A. Al-Shukri Zoology Department, Faculty of Science, Al-Asmarya Islamic University, Libya & Libyan Centre for Sustainable Development Research. Author
  • Fathia M. Senossi Zoology Department, College of Arts and Sciences, AL-Marj, Benghazi University, Libya & Libyan Centre for Sustainable Development Research. Author
  • Hafedah N. Elsharef N. Elsharef Libyan Authority for Scientific Research. Libya & Libyan Centre for Sustainable Development Research. Author
  • Hanan S. Elsharia Zoology Department, College of Arts and Sciences Seluq, Benghazi University, Libya & Libyan Centre for Sustainable Development Research. Author
  • Osama M. El-barasi Zoology Department, Faculty of Science, University of Derna, Libya & Libyan Centre for Sustainable Development Research. Author
  • Samah A. K. Abdallah Zoology Department, Faculty of Science, Omar Al-Mukhtar University, Libya & Libyan Centre for Sustainable Development Research Author
  • Rayya G. Alsultan Biology Department, Education College for Girls. Mosul University, Iraq & Libyan Centre for Sustainable Development Research. Author
  • Noura A. A. Alhissade Microbiology and Immunology Department, Faculty of Pharmacy, University of Derna, Libya & Libyan Centre for Sustainable Development Research. Author
  • Hala Y. M. Hassan Biomedical Engineering Department, Faculty of Engineering, Wadi Alshatti University, Libya & Libyan Centre for Sustainable Development Research Author
  • Mohammed A. Abusharya Biology Department, Faculty of Science, University of Elmergib, Libya & Libyan Centre for Sustainable Development Research Author
  • Samia M. Efkeren Zoology Department, Faculty of Science, Omar Al-Mukhtar University, Libya & Libyan Centre for Sustainable Development Research Author
  • Sana A. A. Mohammed Pathology and Clinical Pathology Department, Faculty of Veterinary Medicine, Omar Al-Mukhtar University, Libya & Libyan Centre for Sustainable Development Research Author
  • Eda M. A. Alshailabi Zoology Department, Faculty of Science, Omar Al-Mukhtar University, Libya & Libyan Centre for Sustainable Development Research. Author

DOI:

https://doi.org/10.33214/5zzyrb61

Keywords:

Aspartame; Libyan Sidr Honey; Nephrotoxicity; Histopathology; Albino Rats

Abstract

Aspartame (ASP) is a widely used artificial sweetener that may induce renal structural alterations following chronic exposure, potentially through oxidative stress–mediated mechanisms. Sidr honey is a natural antioxidant-rich product that may provide protective effects against chemically induced organ damage. In this study, thirty adult female albino rats were randomly allocated into five groups (n = 5): control, Libyan Sidr honey (LSH, 100 mg/kg/body weight/day), ASP (75 mg/kg/body weight/day), protective (LSH for two weeks followed by ASP for four weeks), and combination (LSH and ASP concurrently for four weeks). All treatments were administered orally. At the end of the experiment, serum urea, creatinine, calcium, and uric acid were analyzed, and kidney tissues were examined histologically using a semi-quantitative scoring system. ASP induced marked renal histopathological alterations, including glomerular shrinkage, tubular epithelial degeneration, inflammatory cell infiltration, and vascular congestion. However, no significant changes were observed in serum urea, creatinine, or uric acid levels (p > 0.05). A modest but significant reduction in serum calcium was detected in the combination group (p < 0.05). Both pretreatment and concurrent LSH administration significantly ameliorated ASP-induced renal damage and preserved normal renal architecture. These findings suggest that LSH may exert protective and therapeutic effects against ASP-induced nephrotoxicity.

Abdalally, O. A., Alshailabi, E. M. A., & Ali, M. S. (2021). Effects of vitamin C on liver and kidney enzymes and some biochemical parameters against paracetamol induced hepato-nephrotoxicity in rats. Sirte University Scientific Journal, 12(2), 56–76.

Abdalally, O. A., Khalid, A. M., & Alshailabi, E. M. A. (2026). Histopathological study of N-acetyl-para-aminophenol-induced gastric alterations and ascorbic acid administration in albino rats. The Derna Academy Journal of Applied Science, 5(2), 143–151. https://doi.org/10.71147/853dyn19

Al-Naimi, M. S., Rasheed, H. A., Hussien, N. R., Al Kuraishy, H. M., & Al Gareeb, A. I. (2019). Nephrotoxicity: Role and significance of renal biomarkers in the early detection of acute renal injury. Journal of Advanced Pharmaceutical Technology & Research, 10(3), 95–99. https://doi.org/10.4103/japtr.JAPTR_336_18

Alsaeh, F., Abusharya, M., Alsaeh, E., Baroud, N., & Alsharshary, A. (2025). The harmful effects of aspartame as a food additive on some body organs in laboratory animals: A review. The North African Journal of Scientific Publishing, 3(4), 36–43. https://doi.org/10.65414/najsp.v3i4.656

Alshailabi, E. M. A. (2016). Effects of omeprazole on healing of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulceration in rats and protective role of indole-3-carbinol. Journal of Sciences and Humanities Studies, 12, 174–188.

Alshailabi, E. M. A., Al-Zail, N. I., & Alsalhin, A. A. (2023). Effects of exposure to cigarette smoke on the cardiac tissues in male albino rats and the improvement role of Sidr honey. Bani Waleed University Journal of Humanities and Applied Sciences, 8(3), 261–270. https://doi.org/10.58916/jhas.v8i3.160

Alshailabi, E. M. A., Al-Zail, N. I., & Mohammed, W. E. (2024). The effects of Sidr honey on hepatotoxicity in rats exposed to sidestream cigarette smoke. MINAR International Journal of Applied Sciences and Technology, 6(3). http://dx.doi.org/10.47832/2717-8234.20.40

Alvarez-Suarez, J. M., Tulipani, S., Romandini, S., Bertoli, E., & Battino, M. (2009). Contribution of honey in nutrition and human health: A review. Mediterranean Journal of Nutrition and Metabolism, 3(1), 15–23. https://doi.org/10.3233/s12349-009-0051-6

Allam, W. A., Mahmoud, S. F., & Mahmoud, A. S. (2019). Protective effect of ascorbic acid and N-acetyl cysteine in aspartame induced nephrotoxicity in albino rats. Egypt Journal of Forensic Sciences and Applied Toxicology, 19(1), 107–128. https://doi.org/10.21608/ejfsat.2019.7078.1045

Anderegg, G., Flashka, H., Sallmann, R., & Schwartzenbach, G. (1954). Metallindikatoren VII. Fasciculus, 37, 113.

Azez, O. H., Baker, S. A., Abdullah, M. A., & Nabi, R. K. (2023). Histopathological and dose-dependent effects of aspartame toxicity on liver and kidney of rats. Journal of Applied Veterinary Sciences, 8(2), 16–22. https://dx.doi.org/10.21608/javs.2023.175196.1194

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

Blaine, J., Chonchol, M., & Levi, M. (2014). Renal control of calcium, phosphate, and magnesium homeostasis. Clinical Journal of the American Society of Nephrology, 10(7), 1257–1272. https://doi.org/10.2215/CJN.09750913

Bonny, O., Rubin, A., Huang, C. L., Frawley, W. H., Pak, C. Y., & Moe, O. W. (2008). Mechanism of urinary calcium regulation by urinary magnesium and pH. Journal of the American Society of Nephrology, 19(8), 1530–1537. https://doi.org/10.1681/asn.2007091038

Elduob, R. E. A., Alshailabi, E. M. A., & Efkeren, S. M. (2023). The protective effects of rutin and stem cells against the kidney function changes induced by paracetamol in rats. Sirte University Scientific Journal, 13(2), 53–58. https://doi.org/10.37375/susj.v13i2.2501

Elshama, S., Abdalla, M. E., & Mohamed, A. M. (2018). Role of natural antioxidants in treatment of toxicity. Journal of Toxicological Analysis, 1(1), 3. https://doi.org/10.4172/jta.1000003

Fossati, P., Prencipe, L., & Berti, G. (1980). Use of 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clinical Chemistry, 26, 227.

Gajger, T. I., Dar, S. A., Ahmed, M. M. M., Aly, M. M., & Vlainić, J. (2025). Antioxidant capacity and therapeutic applications of honey: Health benefits, antimicrobial activity and food processing roles. Antioxidants, 14(8), 959. https://doi.org/10.3390/antiox14080959

Haghighat, M., Browning, L., Sirinukunwattana, K., Malacrino, S., Alham, N. K., Colling, R., Cui, Y., Rakha, E., Hamdy, F. C., Verrill, C., & Rittscher, J. (2022). Automated quality assessment of large digitised histology cohorts by artificial intelligence. Scientific Reports, 12, 5002. https://doi.org/10.1038/s41598-022-08351-5

Hall, J. E., & Hall, M. E. (2020). Guyton and Hall textbook of medical physiology (14th ed.). Elsevier.

Hamad, R., Jayakumar, C., Ranganathan, P., Mohamed, R., El-Hamamy, M. M. I., Dessouki, A. A., Ibrahim, A., & Ramesh, G. (2015). Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation. Clinical and Experimental Pharmacology and Physiology, 42(8), 843–848. https://doi.org/10.1111/1440-1681.12433

Humphries, P., Pretorius, E., & Naudé, H. (2008). Direct and indirect cellular effects of aspartame on the brain. European Journal of Clinical Nutrition, 62(4), 451–462. https://doi.org/10.1038/sj.ejcn.1602866

Iyyaswamy, A., & Rathinasamy, S. (2012). Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. Journal of Biosciences, 37(4), 679–688. https://doi.org/10.1007/s12038-012-9236-0

Magnuson, B. A., Burdock, G. A., Doull, J., Kroes, R. M., Marsh, G. M., Pariza, M. W., Spencer, P. S., Waddell, W. J., Walker, R., & Williams, G. M. (2007). Aspartame: A safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Critical Reviews in Toxicology, 37(8), 629–727. https://doi.org/10.1080/10408440701516184

Moshaie-Nezhad, P., Bahari, Z., Jangravi, Z., Zarei, S. M., & Iman, M. J. (2021). The effect of Descurainia sophia seed extract on nephrotoxicity markers induced by acetaminophen in mice. Journal of Advanced Medical and Biomedical Research, 29(134), 139–144. https://doi.org/10.30699/jambs.29.134.139

Mourad, I. M. (2011). Effect of aspartame on some oxidative stress parameters in liver and kidney of rats. African Journal of Pharmacy and Pharmacology, 5(6), 678–682. https://doi.org/10.5897/AJPP10.302

Navaei Alipour, N., Mastali, M., Ferns, G. A., Saberi Karimian, M., & Ghayour Mobarhan, M. (2021). The effects of honey on pro- and anti-inflammatory cytokines: A narrative review. Phytotherapy Research, 35(7), 3690–3701. https://doi.org/10.1002/ptr.7066

Newman, D. J., & Price, C. P. (1999). Renal function and nitrogen metabolites. In C. A. Burtis & E. R. Ashwood (Eds.), Textbook of Clinical Chemistry (3rd ed., pp. 1204–1207). W. B. Saunders.

Omozee, E. B., & Timothy, O. T. (2025). Renal and oxidative consequences of prolonged aspartame and zero sugar soda consumption in rat model. Sokoto Journal of Medical Laboratory Science, 10(3). https://dx.doi.org/10.4314/sokjmls.v10i3.21

Raslan, A. B. M., Tajoury, I. M., & FARAG, M. R. A. (2025). Malunion after Fixation of Intertrochanteeic Fracture by Proximal Cephalomedullry Nail Fixation. Derna Academy Journal for Applied Sciences, 5(2), 133-142.

Stevens, L. A., & Levey, A. S. (2005). Measurement of kidney function. Medical Clinics of North America, 89(3), 457–473. https://doi.org/10.1016/j.mcna.2004.11.009

Thomas, L. (1998). Clinical laboratory diagnostics (1st ed.). Frankfurt: The-Books Verlagsgesellschaft.

Wilczyńska, A., & Żak, N. (2024). Polyphenols as the main compounds influencing the antioxidant effect of honey—A review. International Journal of Molecular Sciences, 25(19), 10606. https://doi.org/10.3390/ijms251910606

Downloads

Published

2026-02-26

Issue

Section

Original Articles

How to Cite

A. Al-Shukri, N., M. Senossi, F., N. Elsharef, H. N. E., S. Elsharia, H., M. El-barasi, O., A. K. Abdallah, S., G. Alsultan, R., A. A. Alhissade, N., Y. M. Hassan, H., A. Abusharya, M., M. Efkeren, S., A. A. Mohammed, S., & M. A. Alshailabi, E. (2026). Protective and Therapeutic Effects of Libyan Sidr Honey on Aspartame-Induced Nephrotoxicity in Adult Albino Rats A Histopathological Study. Medical Technology Journal of Applied Science, 2(1), 44-56. https://doi.org/10.33214/5zzyrb61

Similar Articles

You may also start an advanced similarity search for this article.