Cardiac Histopathological Changes Induced by N-acetyl-para-aminophenol and the Protective Effect of Vitamin C in Albino Rats

Ahlaam M.  Khalid; Ola A.  Abdalally; Eda M.A. Alshailabi

doi:10.54172/5t4gqx33

Authors

Ahlaam M. Khalid Laboratory Department, Higher Institute of Medical Sciences and Technology, Libya Author
Ola A. Abdalally Almahara institute for the medical and managerial sciences, Libya Author
Eda M.A. Alshailabi Department of Zoology, Faculty of Science, Omar Al-Mukhtar University, Libya Author

DOI:

https://doi.org/10.54172/5t4gqx33

Keywords:

N-acetyl-para-aminophenol, Vitamin C, Cardiac tissue, Rats, Histo-pathology.

Abstract

N-acetyl-para-aminophenol (NAPA), or paracetamol, is a widely used antipyretic and analgesic; however, high doses can harm the heart, mainly through oxidative stress. This study aimed to examine the cardiac histopathological changes induced by NAPA and the protective effect of vitamin C (VC) in albino rats. Rats were randomly divided into five groups: control, VC (500 mg/kg b.w. for two weeks), NAPA (500 mg/kg b.w. for two weeks), (NAPA + VC) co-treated for two weeks, and a protective group that received VC for one week before NAPA exposure for one week. Histological examination showed that NAPA induced significant myocardial alterations, including disorganized myocardial fibers, cellular deterioration, and vascular congestion. Moreover, the co-treated rats displayed reduced histopathological alterations, while the protective group showed even stronger protection for cardiac tissue. These results suggest that VC exerts a cardioprotective effect against NAPA-induced heart injury, possibly due to its antioxidant properties. Furthermore, the findings highlight the potential of VC as both a preventive and therapeutic strategy against NAPA-related cardiotoxicity.

References

Adeneye, A. A., & Olagunju, J. O. (2008). Protective effect of oral ascorbic acid (vitamin C) against acetaminophen-induced hepatic injury in rats. African Journal of Biomedical Re-search, 11, 183–190. https://doi.org/10.4314/ajbr.v11i2.50704

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

Alshailabi, E. M. A., Abdalally, O. A., & Mohammed, F. A. (2024). The protective role of ascor-bic acid on the testis tissues damage induced by paracetamol in albino rats. Al-Kitab Journal for Pure Sciences, 8(1), 19–28. https://doi.org/10.32441/kjps.08.01.p3

Ayoub, S. S. (2021). Paracetamol (acetaminophen): A familiar drug with an unexplained mecha-nism of action. Temperature, 8(4), 351–371. https://doi.org/10.1080/23328940.2021.1886392

Carr, A. C., & Frei, B. (1999). Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. The American Journal of Clinical Nutrition, 69(6), 1086–1107. https://doi.org/10.1093/ajcn/69.6.1086

Destere, A., Merino, D., Lavrut, T., Rocher, F., Viard, D., Drici, M.-D., & Gérard, A. O. (2024). Drug-induced cardiac toxicity and adverse drug reactions, a narrative review. Therapie, 79(2), 161–172. https://doi.org/10.1016/j.therap.2023.10.008

D'Oria, R., Schipani, R., Leonardini, A., Natalicchio, A., Perrini, S., Cignarelli, A., Laviola, L., & Giorgino, F. (2020). The role of oxidative stress in cardiac disease: From physiological re-sponse to injury factor. Oxidative Medicine and Cellular Longevity, 2020, 5732956. https://doi.org/10.1155/2020/5732956

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

Han, D., Wang, F., & Shen, D. (2024). Nanomedicines as guardians of the heart: Unleashing the power of antioxidants to alleviate myocardial ischemic injury. Theranostics, 14(13), 5336–5370. https://doi.org/10.7150/thno.99961

Indumathi, M. C., Swetha, K., Abhilasha, K. V., Siddappa, S., Manjula Kumar, S., Prasad, G. K., Chen, C.-H., & Marathe, G. K. (2024). Selenium ameliorates acetaminophen-induced oxida-tive stress via MAPK and Nrf2 pathways in mice. Biological Trace Element Research, 202(6), 2598–2615. https://doi.org/10.1007/s12011-023-03845-3

Jin, S. M., & Park, K. (2012). Acetaminophen induced cytotoxicity and altered gene expression in cultured cardiomyocytes of H9C2 cells. Environmental Health and Toxicology, 27, e2012011. https://doi.org/10.5620/eht.2012.27.e2012011

Kennon-McGill, S., & McGill, M. R. (2017). Extrahepatic toxicity of acetaminophen: Critical evaluation of the evidence and proposed mechanisms. Journal of Clinical and Translational Research, 3(3), 297–310. https://doi.org/10.18053/jctres.03.201703.005

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

Mladěnka, P., Applová, L., Patočka, J., Costa, V. M., Remião, F., Pourová, J., Mladěnka, A., Karlíčková, J., Jahodář, L., Vopršalová, M., Varner, K. J., & Štěrba, M. (2018). Comprehen-sive review of cardiovascular toxicity of drugs and related agents. Medicinal Research Re-views, 38(4), 1332–1403. https://doi.org/10.1002/med.21476

Modo, E., Okwandu, N., & Dongo, B. (2015). Comparative effects of vitamin C and vitamin E pre-treatment in acute paracetamol induced toxicity on the liver of rats. World Journal of Pharmaceutical Sciences, 3(3), 407–412.

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

Netala, V. R., Teertam, S. K., Li, H., & Zhang, Z. (2024). A comprehensive review of cardiovascu-lar disease management: Cardiac biomarkers, imaging modalities, pharmacotherapy, surgi-cal interventions, and herbal remedies. Cells, 13(17), 1471. https://doi.org/10.3390/cells13171471

Okiljević, B., Martić, N., Govedarica, S., Andrejić Višnjić, B., Bosanac, M., Baljak, J., Pavlić, B., Milanović, I., & Rašković, A. (2024). Cardioprotective and hepatoprotective potential of si-lymarin in paracetamol-induced oxidative stress. Pharmaceutics, 16(4), 520. https://doi.org/10.3390/pharmaceutics16040520

Prescott, L. F. (2000). Paracetamol: Past, present, and future. American Journal of Therapeutics, 7(2), 143–147.

Rahaman, M. M., Sharmin, S., Atolani, O., Adeyemi, O. S., & Islam, M. T. (2021). Protective ef-fect of naturally-derived antioxidants against acetaminophen-induced hepatotoxicity: A re-view. Acta Biologica Marisiensis, 3(2), 36–47. https://doi.org/10.2478/abmj-2020-0009

Ralapanawa, U., Jayawickreme, K. P., Ekanayake, E. M. M., & Dissanayake, A. M. S. D. M. (2016). A study on paracetamol cardiotoxicity. BMC Pharmacology and Toxicology, 17, 30. https://doi.org/10.1186/s40360-016-0073-x

Ramachandran, A., & Jaeschke, H. (2019). Acetaminophen hepatotoxicity. Seminars in Liver Dis-ease, 39(2), 221–234. https://doi.org/10.1055/s-0039-1679919

Shati, A. A., Zaki, M. S. A., Alqahtani, Y. A., Haidara, M. A., Al-Shraim, M., Dawood, A. F., & Eid, R. A. (2022). Potential protective effect of vitamin C on quinalphos-induced cardiac toxicity: Histological and tissue biomarker assay. Biomedicines, 10(1), 39. https://doi.org/10.3390/biomedicines10010039

Xu, Y., Zheng, H., Slabu, I., Liehn, E. A., & Rusu, M. (2025). Vitamin C in cardiovascular disease: From molecular mechanisms to clinical evidence and therapeutic applications. Antioxidants, 14(5), 506. https://doi.org/10.3390/antiox14050506

Zheng, H., Xu, Y., Liehn, E. A., & Rusu, M. (2024). Vitamin C as scavenger of reactive oxygen species during healing after myocardial infarction. International Journal of Molecular Sci-ences, 25(6), 3114. https://doi.org/10.3390/ijms25063114