Logo

Myocardial Structural Remodeling and Histological Recovery Following Acetaminophen Exposure: Comparative Effects of Rutin and Mesenchymal Stem Cells in Male Rats

Authors
  • Rabha E. A. EL-Dab

    Department of Zoology, Faculty of Science, Omar Al-Mukhtar University, Libya
    Author
  • Eda M. A. Alshailabi

    Department of Zoology, Faculty of Science, Omar Al-Mukhtar University, Libya.
    Author
Keywords:
Acetaminophen; Myocardium; Rutin; Mesenchymal stem cells; Histopathology; Myocardial injury
Abstract

Acetaminophen (APAP) is a commonly used analgesic and antipyretic drug, but excessive exposure can cause tissue injury and may affect organs beyond the liver. This study investigated myocardial (MYO) histopathological alterations associated with repeated APAP exposure in male albino rats and compared the protective effects of rutin (RUT) and bone marrow-derived mesenchymal stem cells (BM-MSCs). Fifty adult male rats were randomly assigned to control and experimental groups. APAP was administered orally at 750 mg/kg b.wt., every 72 hours for 21 days. Following APAP exposure, animals were either monitored for spontaneous recovery or treated with RUT, BM-MSCs, or their combination for 30 and 60 days. Heart tissues were processed and stained with hematoxylin and eosin for histopathological examination, and the observed alterations were evaluated using semi-quantitative grading. APAP exposure resulted in progressive MYO injury, characterized by MYO degeneration, subendocardial and interstitial edema, focal hemorrhage, and inflammatory cell infiltration, with more pronounced alterations after 60 days. RUT treatment was associated with progressive improvement in MYO structure, reaching complete histological normalization after 60 days. BM-MSC treatment resulted in well-preserved MYO architecture at both examination periods, with no detectable histopathological alterations. Combined treatment also maintained relatively preserved MYO architecture; however, mild focal degeneration persisted at both time points. Overall, RUT and BM-MSCs demonstrated substantial histological protective effects against APAP-associated MYO injury, although the combined regimen did not provide an additional histological advantage over the individual treatments

Downloads
Download data is not yet available.
References

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, 11(2), 59–76.

Ahmed, A., Mohammed, S., Alshailabi, E., & Khaled, F. (2026). Histological effects of Ziziphus spina-christi leaf extract on testes and epididymides in male rabbits. Wadi Alshatti University Journal of Pure and Applied Sciences, 4(1), 238–244. https://doi.org/10.63318/waujpasv4i1_25 DOI: https://doi.org/10.63318/waujpasv4i1_25

Alshailabi, E. M., Abdalally, O. A., & Mohammed, F. A. (2024). The protective role of ascorbic acid on the testis tissue damage induced by paracetamol in albino rats. Al-Kitab Journal for Pure Sciences, 8(01), 19–28. https://doi.org/10.32441/kjps.08.01.p3 DOI: https://doi.org/10.32441/kjps.08.01.p3

Anbarasu, C., Rajkapoor, B., & Kalpana, J. (2011). Protective effect of Pisonia aculeata on paracetamol-induced hepatotoxicity in rats. Journal of Experimental and Integrative Medicine, 1(3), 167–172. https://doi.org/10.5455/jeim.040511.or.008 DOI: https://doi.org/10.5455/jeim.040511.or.008

Annapurna, A., Reddy, C. S., Akondi, R. B., & Rao, S. R. C. (2010). Cardioprotective actions of quercetin and rutin in experimental myocardial infarction in rats. Journal of Pharmacy and Pharmacology, 61(10), 1365–1374. https://doi.org/10.1211/jpp.61.10.0014 DOI: https://doi.org/10.1211/jpp.61.10.0014

Bancroft, J. D., & Stevens, A. (1996). Theory and practice of histological techniques (4th ed.). Churchill Livingstone.

Bochwal, N. R., Ibrahim, H. M., Abdelsameh, E. Y., Nweh, W. A., Ahmed, S. F., Shref, N. S., ... & Mohammed, N. M. (2026). The Role of MRI in Diagnosing Brain Tumors. Derna Academy Journal for Applied Sciences, 7(1), 95-100. DOI: https://doi.org/10.71147/vp4bg060

El-Dab, R. E. A., & Alshailabi, E. M. A. (2024). Histopathological evaluation of the potential ameliorating effects of stem cells and rutin against acute renal toxicity induced by acetaminophen in male rats. International Science and Technology Journal, 1(34), 1–17. https://doi.org/10.62341/reho4630 DOI: https://doi.org/10.62341/reho4630

El-Nahrawy, A. M., Abu Zahra, F. A., & El-Dab, R. E. A. (2017). Ameliorative role of bone marrow mesenchymal stem cells and rutin against acetaminophen-induced hepatotoxicity in adult male rats. International Journal of Advanced Research, 5(9), 450–459. https://doi.org/10.21474/IJAR01/5349 DOI: https://doi.org/10.21474/IJAR01/5349

Elduob, R. E. A., Alshailabi, E. M. A., & Efkeren, S. M. (2023a). Cardioprotective effects of rutin and mesenchymal stem cells on acetaminophen-induced cardiac enzymatic damage in rats. Global Libyan Journal, 70(3), 1–14. https://doi.org/10.37376/glj.vi70.4541 DOI: https://doi.org/10.37376/glj.vi70.4541

Elduob, R. E. A., Alshailabi, E. M. A., & Efkeren, S. M. (2023b). 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

Fernández-Jiménez, R., Sánchez-González, J., Agüero, J., García-Prieto, J., López-Martín, G. J., García-Ruiz, J. M., Molina-Iracheta, A., Rosselló, X., Fernández-Friera, L., Pizarro, G., García-Álvarez, A., Dall’Armellina, E., Macaya, C., Choudhury, R. P., Fuster, V., & Ibáñez, B. (2015). Myocardial edema after ischemia/reperfusion is not stable and follows a bimodal pattern. Journal of the American College of Cardiology, 65(4), 315–323. https://doi.org/10.1016/j.jacc.2014.11.004 DOI: https://doi.org/10.1016/j.jacc.2014.11.004

Jin, S. M., Kil, H. R., Park, K., & Noh, C. I. (2012). Gene expression in rat hearts following oral administration of a hepatotoxic dose of acetaminophen. Yonsei Medical Journal, 53(1), 172–180. https://doi.org/10.3349/ymj.2012.53.1.172 DOI: https://doi.org/10.3349/ymj.2012.53.1.172

Jiang, W., Ma, A., Wang, T., Han, K., Liu, Y., Zhang, Y., Zhao, X., Dong, A., Du, Y., Huang, X., Wang, J., Lei, X., & Zheng, X. (2006). Intravenous transplantation of mesenchymal stem cells improves cardiac performance after myocardial ischemia in rats. Transplantation International, 19(7), 570–580. https://doi.org/10.1111/j.1432-2277.2006.00307.x DOI: https://doi.org/10.1111/j.1432-2277.2006.00307.x

Karthick, M., & Prince, P. S. M. (2006). Preventive effect of rutin on lipid peroxidation in myocardial infarction in rats. Journal of Pharmacy and Pharmacology, 58(5), 701–707. https://doi.org/10.1211/jpp.58.5.0016 DOI: https://doi.org/10.1211/jpp.58.5.0016

KhabazianZadeh, F., Kazemi, T., Nakhaee, S., Ng, P. C., & Mehrpour, O. (2019). Acetaminophen poisoning-induced heart injury: A case-based review. DARU Journal of Pharmaceutical Sciences, 27(2), 839–851. https://doi.org/10.1007/s40199-019-00307-x DOI: https://doi.org/10.1007/s40199-019-00307-x

Khalid, A. M., Abdalally, O. A., & Alshailabi, E. M. A. (2026). Cardiac histopathological changes induced by N-acetyl-para-aminophenol and the protective effect of vitamin C in albino rats. Medical Journal of Biomedical Sciences, 24(1). https://doi.org/10.54172/5t4gqx33

Lillie, R. D. (1954). Histopathological techniques and histochemistry (3rd ed.). New York, USA: McGraw-Hill.

Mabotuwana, N. S., Rech, L., Lim, J., Hardy, S. A., Murtha, L. A., Rainer, P. P., & Boyle, A. J. (2022). Paracrine factors released by mesenchymal stem cells and their cardiovascular effects: A systematic review. Stem Cell Reviews and Reports, 18(8), 2606–2628. https://doi.org/10.1007/s12015-022-10429-6 DOI: https://doi.org/10.1007/s12015-022-10429-6

Meng, X.-L., Yu, M.-M., Liu, Y.-C., Chai, Y.-F., et al. (2022). Rutin inhibits cardiac apoptosis and prevents sepsis-induced cardiomyopathy. Frontiers in Physiology, 13, 834077. https://doi.org/10.3389/fphys.2022.834077 DOI: https://doi.org/10.3389/fphys.2022.834077

Nagai, T., Inomata, T., Kohno, T., et al. (2023). JCS 2023 guideline on myocarditis. Circulation Journal, 87(5), 674–754. https://doi.org/10.1253/circj.CJ-22-0696 DOI: https://doi.org/10.1253/circj.CJ-22-0696

Oskouei, B. N., Lamirault, G., Joseph, C., et al. (2012). Increased potency of cardiac stem cells compared with bone marrow mesenchymal stem cells. Stem Cells Translational Medicine, 1(2), 116–124. https://doi.org/10.5966/sctm.2011-0015 DOI: https://doi.org/10.5966/sctm.2011-0015

Rahmani, S., Naraki, K., Roohbakhsh, A., Hayes, A. W., & Karimi, G. (2023). Protective effects of rutin on organ toxicity. Food Science & Nutrition, 11(1), 39–56. https://doi.org/10.1002/fsn3.3041 DOI: https://doi.org/10.1002/fsn3.3041

Ramachandran, A., & Jaeschke, H. (2017). Mechanisms of acetaminophen hepatotoxicity. Journal of Clinical and Translational Research, 3(Suppl. 1), 157–169. https://doi.org/10.18053/jctres.03.2017S1.002 DOI: https://doi.org/10.18053/jctres.03.2017S1.002

Shenbagam, M., & Nalini, N. (2011). Dose-response effect of rutin on oxidative imbalance. Fundamental & Clinical Pharmacology, 25, 493–502. https://doi.org/10.1111/j.1472-8206.2010.00861.x DOI: https://doi.org/10.1111/j.1472-8206.2010.00861.x

Salama, H. (2026). Effectiveness of Speech Language Pathology Interventions in Managing Hypokinetic Dysarthria in Parkinson's Disease: A Comprehensive Systematic Review. Derna Academy Journal for Applied Sciences, 6(2), 90-95. DOI: https://doi.org/10.71147/ksncc516

Sid-Otmane, C., Perrault, L. P., & Ly, H. Q. (2020). Mesenchymal stem cells in cardiac repair. Journal of Translational Medicine, 18(1), 336. https://doi.org/10.1186/s12967-020-02504-8 DOI: https://doi.org/10.1186/s12967-020-02504-8

Wang, Y.-D., Zhang, Y., Sun, B., Leng, X.-W., Li, Y.-J., & Ren, L.-Q. (2018). Cardioprotective effects of rutin in rats. Journal of Asian Natural Products Research, 20(4), 361–373. https://doi.org/10.1080/10286020.2017.1394292 DOI: https://doi.org/10.1080/10286020.2017.1394292

Yoon, E., Babar, A., Choudhary, M., Kutner, M., & Pyrsopoulos, N. (2016). Acetaminophen-induced hepatotoxicity: A comprehensive update. Journal of Clinical and Translational Hepatology, 4(2), 131–142. https://doi.org/10.14218/JCTH.2015.00052 DOI: https://doi.org/10.14218/JCTH.2015.00052

Downloads
Published
2026-09-28
Section
Original Articles

How to Cite

Myocardial Structural Remodeling and Histological Recovery Following Acetaminophen Exposure: Comparative Effects of Rutin and Mesenchymal Stem Cells in Male Rats. (2026). Derna Academy Journal for Applied Sciences, 7(2), 221-229. https://doi.org/10.71147/esnkvs68

Similar Articles

11-17 of 17

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