Histopathological Evaluation of Aspartame-Induced Cardiotoxicity and the Protective Role of Libyan Sidr Honey in Albino Rats

Authors

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

DOI:

https://doi.org/10.65405/mq82qy39

Keywords:

Aspartame; Sidr honey; Cardiotoxicity; Histopathology; Albino rats

Abstract

Aspartame (ASP) is one of the most commonly used artificial sweeteners worldwide. Although it is generally regarded as safe when consumed within recommended limits, growing evidence suggests that prolonged exposure may contribute to oxidative stress and tissue damage. The present study was designed to investigate the potential cardiotoxic effects of ASP, as well as the protective role of Libyan Sidr honey (SH), in female albino rats through histopathological assessment. A total of twenty-five adult female albino rats were randomly divided into five groups (n = 5 per group): a control group, an SH-treated group (100 mg/kg/day), an ASP-treated group (75 mg/kg/day), a protective group (SH administered for two weeks followed by ASP for four weeks), and a combination group receiving both SH and ASP simultaneously for four weeks. All treatments were administered orally. Histopathological examination, supported by semi-quantitative scoring (– = absent, + = mild, ++ = moderate, +++ = severe), revealed that ASP exposure induced marked myocardial damage. These alterations included disruption of cardiac muscle fibers, pronounced vascular congestion (+++), inflammatory cell penetration (++), hemorrhage (+++), and areas of focal necrosis. In contrast, rats treated with SH alone maintained normal cardiac tissue architecture. The protective group demonstrated partial improvement, with moderate levels of vascular congestion (++) and hemorrhage (++). Notably, the combination group showed the most significant preservation of myocardial structure, with only mild changes observed across all evaluated parameters (+). Overall, these findings suggest that concurrent administration of Libyan SH can effectively attenuate ASP-induced cardiotoxicity. This highlights its potential as a natural cardioprotective agent. However, further investigations incorporating biochemical and molecular analyses are needed to better understand the mechanisms underlying these protective effects.

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References

[1] 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

[2] Al-Shukri, N. A., Senossi, F. M., Elsharef, H. N., Elsharia, H. S., El-Barasi, O. M., Abdallah, S. A. K., Alsultan, R. G., Alhissade, N. A. A., Hassan, H. Y. M., Abusharya, M. A., Efkeren, S. M., Mohammed, S. A. A., & Alshailabi, E. M. A. (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

[3] Sylvetsky, A. C., & Rother, K. I. (2018). Nonnutritive sweeteners in weight management and chronic disease: A review. Obesity, 26(4), 635–640. https://doi.org/10.1002/oby.22139

[4] 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

[5] World Health Organization. (2023, July 14). Aspartame hazard and risk assessment results released. https://www.who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released

[6] Moftah, O. M. Y., Gadallah, A. A., Elemam, S. I. A., & El-Sayyad, H. I. H. (2020). Impairment of hepatic, cardiac and lung tissues in aspartame-treated male Wistar albino rats. East African Scholars Journal of Medical Sciences, 3(2), 45–55. https://doi.org/10.36349/EASMS.2020.v03i02.003

[7] Butchko, H. H., Stargel, W. W., Comer, C. P., Mayhew, D. A., Benninger, C., Blackburn, G. L., de Sonneville, L. M. J., Geha, R. S., Hertelendy, Z., Koestner, A., Leon, A. S., Liepa, G. U., McMartin, K. E., Mendenhall, C. L., Munro, I. C., Novotny, E. J., Renwick, A. G., Schiffman, S. S., Schomer, D. L., Shaywitz, B. A., & Thomas, J. A. (2002). Aspartame: Review of safety. Regulatory Toxicology and Pharmacology, 35(2), S1–S93. https://doi.org/10.1006/rtph.2002.1542

[8] 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

[9] Münzel, T., Gori, T., Keaney, J. F., Jr., Maack, C., & Daiber, A. (2015). Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. European Heart Journal, 36(38), 2555–2564. https://doi.org/10.1093/eurheartj/ehv305

[10] Wang, W., & Kang, P. M. (2020). Oxidative stress and antioxidant treatments in cardiovascular diseases. Antioxidants (Basel), 9(12), 1292. https://doi.org/10.3390/antiox9121292

[11] Choudhary, A. K., Sundareswaran, L., & Sheela Devi, R. (2016). Aspartame induced cardiac oxidative stress in Wistar albino rats. Nutrition Clinique et Métabolisme, 30(1), 29–37. https://doi.org/10.1016/j.nupar.2016.01.071

[12] Anbara, H., Kian, M., Darya, G.-H., & Sheibani, M. T. (2022). Long-term intake of aspartame-induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and triggers P53-dependent apoptosis in a mouse model. International Journal of Experimental Pathology, 103(6), 252–262. https://doi.org/10.1111/iep.12458

[13] 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

[14] 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

[15] Ahmed, A. I., Mohammed, S. A. A., Alshailabi, E. M. A., & Khaled, F. A. (2026). Histological effects of Ziziphus spina-christi leaf extract. Wadi Alshatti University Journal of Pure and Applied Sciences, 4(1), 238–244. https://doi.org/10.63318/waujpasv4i1_25

[16] Özkök, D., & Silici, S. (2017). Antioxidant activities of honeybee products. Food Science and Biotechnology, 26(1), 201–206. https://doi.org/10.1007/s10068-017-0027-0

[17] Idrus, R. B. H., Sainik, N. Q. A. V., Nordin, A., Saim, A. B., & Sulaiman, N. (2020). Cardioprotective effects of honey and its constituent: An evidence-based review of laboratory studies and clinical trials. International Journal of Environmental Research and Public Health, 17(10), 3613. https://doi.org/10.3390/ijerph17103613

[18] Lewoyehu, M., & Amare, M. (2019). Comparative evaluation of analytical methods for determining the antioxidant activities of honey: A review. Cogent Food & Agriculture, 5(1), 1685059. https://doi.org/10.1080/23311932.2019.1685059

[19] Alshailabi, E. M. A., Al-Zail, N. I., & Darwesh, N. M. (2023). Effect of Libyan Sidr honey on thyroid gland damage induced by cigarette smoke in male rats. Sebha University Journal of Pure & Applied Sciences, 22(3). https://doi.org/10.51984/JOPAS.V22I3.2752

[20] 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

[21] Prendergast, B. J., Onishi, K. G., & Zucker, I. (2014). Female mice inclusion in research. Neuroscience & Biobehavioral Reviews, 40, 1–5. https://doi.org/10.1016/j.neubiorev.2014.01.001

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

[23] 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 histology using AI. Scientific Reports, 12, 5002. https://doi.org/10.1038/s41598-022-08351-5

[24] Alshailabi, E. M. A., Abdalally, O. A., & Majeed, S. F. (2021). Histopathological study on the protective effect of vitamin C against paracetamol-induced acute hepatic damage in rat. Global Libyan Journal, 53, 1–15. https://doi.org/10.37376/glj.vi53.1645

[25] 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

[26] Angelini, A., Pi, X., & Xie, L. (2017). Dioxygen and metabolism in cardiac function. Frontiers in Physiology, 8, 1044. https://doi.org/10.3389/fphys.2017.01044

[27] Al Tamim, A., Alshammari, G. M., Yagoub, A. E., Saleh, A., Mohammed, M. A., & Yahya, M. A. (2025). Protective effect of Saudi Arabian honey against obesity. Frontiers in Nutrition, 12, 1582408. https://doi.org/10.3389/fnut.2025.1582408

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Published

2026-05-12

Issue

Vol. 10 No. 40 (2026): المجلد 10 العدد 40 مايو 2026

Section

المقالات

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How to Cite

Histopathological Evaluation of Aspartame-Induced Cardiotoxicity and the Protective Role of Libyan Sidr Honey in Albino Rats. (2026). Comprehensive Journal of Science, 10(40), 284-303. https://doi.org/10.65405/mq82qy39