Hepatoprotective effect of N-acetylcysteine against augmentin-induced biochemical alterations of liver function in rats
DOI:
https://doi.org/10.30539/rz7p2s14Keywords:
Augmentin, hepatotoxicity, liver, N-acetylcysteineAbstract
Background: Augmentin is a common antibiotic that can cause liver injury. It increases oxidative stress and damages liver cells. N-acetylcysteine (NAC) is known for its antioxidant and protective effects on the liver. This study aimed to evaluate the protective role of NAC against augmentin-induced liver damage in rats by measuring biochemical markers, oxidative stress indices, lipid profile, and histopathology. Methodology: Forty male rats were divided into four groups (10 each). Control group received basal diet. T1 received augmentin (30 mg/kg/day). T2 received NAC (150 mg/kg/day). T3 received NAC plus augmentin at the same doses. Oral treatments lasted for 5 weeks. Blood samples were collected for biochemical tests (liver function enzymes and lipid profile). Results: The animals of T1 group showed a significant (p < 0.05) rise of liver enzymes, and lipid profile parameters, and a decrease in HDL, total protein and albumin as compared with the control. While T2 depicted a significant correction of these alterations toward the control values (p < 0.05). T3 explained a significant improvement in liver enzymes, lipid profile, and bilirubin, approaching control levels (p < 0.05). Conclusions: NAC effectively reduced augmentin-induced biochemical and histological liver damage. It has antioxidant, anti-inflammatory, and lipid-stabilizing effects. NAC may be considered as a supportive therapy in drug-induced hepatotoxicity.
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Albeltagy, R. S., Mumtaz, F., Abdel Moneim, A. E., & El-Habit, O. H. (2021). N-acetylcysteine reduces miR-146a and NF-κB p65 inflammatory signaling following cadmium hepatotoxicity in rats. Biological Trace Element Research, 199, 4657-4665. https://doi.org/10.1007/s12011-020-02443-3
Aldini, G., Altomare, A., Baron, G., Vistoli, G., Carini, M., Borsani, L., & Reggiani, F. (2018). N-acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radical Research, 52(7), 751-762. https://doi.org/10.1080/10715762.2018.1468564
Ameri, A., Rahmati, A., Soroushfar, S., Lalehzari, M., & Dehghani. (2024). Effect of N-acetylcysteine against deltamethrin-induced hepatotoxicity in mice. Avicenna Journal of Medical Biotechnology, 16(2), 88–95. https://doi.org/10.18502/ajmb.v16i2.14859
Appiah, J., Prasad, A., Shah, V., Patel, V., Fareen, N., Marin, A. C., & Cheriyath, P. (2023). Amoxicillin-clavulanate induced liver injury in a young female. Cureus, 15(1), e33421. https://doi.org/10.7759/cureus.33421
Ayala, A., Muñoz, M. F., & Argüelles, S. (2014). Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity, 2014, 360438. https://doi.org/10.1155/2014/360438
Chiang, J. Y., & Ferrell, J. M. (2020). Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis. Liver Research, 4(2), 47-63. https://doi.org/10.1016/j.livres.2020.05.001
Delemos, A. S., Ghabril, M., Rockey, D. C., Gu, J., Barnhart, H. X., Fontana, R. J., ... & DILIN. (2016). Amoxicillin–clavulanate-induced liver injury. Digestive Diseases and Sciences, 61(8), 2406-2416. https://doi.org/10.1007/s10620-016-4154-1
Ding, W., Fan, J. H., Zhong, L. R., Wang, N. X., Liu, L. H., Zhang, H. B., ... & Wei, A. Y. (2024). N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress. Asian Journal of Andrology, 26(1), 99-106. https://doi.org/10.4103/aja202414
El-Kholy, W. M., Hemieda, F. A., & Elabani, G. M. (2019). Role of cinnamon extract in protection against amoxicillin/clavulanate-induced liver damage in rats. IOSR-JPBS, 14(1), 14-21.
Galicia-Moreno, M., Monroy-Ramirez, H. C., Caloca-Camarena, F., Arceo-Orozco, S., Muriel, P., Sandoval-Rodriguez, A., & Armendariz-Borunda, J. (2024). A new opportunity for N-acetylcysteine in liver diseases: Antioxidant and epigenetic effects. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(1), 1–22. https://doi.org/10.1007/s00210-024-02511-2
Haryanti, N., Heriansyah, T., Yusuf, H., Mudatsir, M., & Zulkarnaen, Z. (2025). Dose and duration of N-acetylcysteine on superoxide dismutase, MCP-1, and foam cell in atherosclerosis rat model. Tropical Journal of Natural Product Research, 9(3). https://doi.org/10.26538/tjnpr/v9i3.45
Lee, D. H., Blomhoff, R., & Jacobs, D. R. (2004). Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radical Research, 38(6), 535-539. https://doi.org/10.1080/10715760410001694026
Liu, X., Wang, L., Cai, J., Liu, K., Liu, M., Wang, H., & Zhang, H. (2019). N-acetylcysteine alleviates H2O2-induced damage via regulating the redox status of intracellular antioxidants in H9c2 cells. International Journal of Molecular Medicine, 43(1), 199-208. https://doi.org/10.3892/ijmm.2018.3962
Mahmoudinezhad, M., Ghavami, Z., Jamilian, P., Zarezadeh, M., & Ostadrahimi, A. (2023). The effect of N-acetylcysteine supplementation on endothelial function: A systematic review. Clinical Nutrition Open Science, 52, 136-150. https://doi.org/10.1016/j.nutos.2023.10.003
Moreno-Torres, M., López-Pascual, E., Rapisarda, A., Quintás, G., Drees, A., Steffensen, I. L.,... & Jover, R. (2024). Novel clinical phenotypes and outcome prediction in drug-induced cholestasis. Biomedicine and Pharmacotherapy, 174, 116530. https://doi.org/10.1016/j.biopha.2024.116530
Mulu, Z., & Birhanu, Y. (2024). A case of amoxicillin/clavulanate induced prolonged cholestatic liver injury. Journal of Clinical Images Medical Case Reports, 5(11), 3342.
Nikbaf-Shandiz, M., Adeli, S., Faghfouri, A. H., Khademi, F., Jamilian, P., Zarezadeh, M., & Ebrahimi-Mamaghani, M. (2023). The efficacy of N-acetylcysteine in improving liver function: A systematic review and meta-analysis. PharmaNutrition, 24, 100343. https://doi.org/10.1016/j.phanu.2023.100343
Ribeiro, B. (2023). Glutathione: The master antioxidant. Ozone Therapy Global Journal, 13(1), 175-197. https://doi.org/10.13140/RG.2.2.19576.05120
Ali, M., Khan, T., Fatima, K., Ali, Q. U. A., Ovais, M., Khalil, A. T. & Idrees, M. (2018). Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions. Phytotherapy Research, 32(2), 199-215.
Shajari R, Zavar Reza J, Najafi F, Hemayati R. (2025). The effect of N-acetylcysteine on inflammatory and oxidative markers in patients receiving hemodialysis; a single-arm clinical trial study. Journal of Nephropharmacology, 14(1):e12746. https://doi.org/10.34172/npj.2025.12746
Sukumaran, D., Usharani, P., Paramjyothi, G. K., Subbalaxmi, M. V. S., Sireesha, K., & Ali, M. A. (2023). Hepatoprotective effect of N-acetylcysteine on anti-tuberculosis drug-induced hepatotoxicity. Indian Journal of Tuberculosis, 70 (3), 303-310. https://doi.org/10.1016/j.ijtb.2022.05.012
Teschke, R., Eickhoff, A., Schulze, J., & Danan, G. (2021). Herb-induced liver injury with worldwide cases assessed by RUCAM. Translational Gastroenterology and Hepatology, 6, 51.
Timor-López, E., Tolosa, L., & Donato, M. T. (2025). Cell-based approaches for understanding drug-induced cholestatic liver injury. Archives of Toxicology, 99(1), 1-18. https://doi.org/10.1007/s00204-025-04016-0
Zavala-Valencia, A. C., Velasco-Hidalgo, L., Martínez-Avalos, A., Castillejos-López, M., & Torres-Espíndola, L. M. (2024). Effect of N-acetylcysteine on cisplatin toxicity: A review. Biologics: Targets and Therapy, 18, 7-19. https://doi.org/10.2147/btt.s438150
Zhuang, X., Li, L., Liu, T., Zhang, R., Yang, P., Wang, X., & Dai, L. (2022). Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural ingredients, A review. Frontiers in Pharmacology, 13, 1037814. https://doi.org/10.3389/fphar.2022.1037814
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