Mohammed Maseer Jasim (1), Nadheerah F Neamah (2), Waleed Khaled Ghanem (3)
General Background: Liver toxicity remains a critical adverse effect of many chemotherapeutic agents, significantly limiting their clinical utility. Specific Background: Paclitaxel, a potent anticancer drug, is known to induce hepatic injury through oxidative stress, inflammation, and apoptosis. However, effective strategies to prevent such hepatotoxicity are limited. Knowledge Gap: While rutin, a natural flavonoid, exhibits antioxidant and anti-inflammatory effects, its protective role against paclitaxel-induced liver injury has not been fully elucidated in vivo. Aims: This study aimed to investigate the hepatoprotective potential of rutin against paclitaxel-induced hepatic damage in male rats through biochemical, oxidative, and histopathological assessments. Results: Rutin administration markedly reduced serum ALT, AST, and MDA levels while increasing GPx activity, restoring hepatic architecture, and alleviating necrosis, sinusoidal congestion, and apoptosis compared with paclitaxel-only groups. Novelty: This study provides novel experimental evidence demonstrating that rutin counteracts chemotherapy-induced hepatotoxicity primarily via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Implications: The findings suggest that rutin could serve as a promising adjunctive therapy to protect against drug-induced liver injury in cancer patients undergoing paclitaxel treatment, warranting further clinical evaluation.Highlight :
Rutin reduced oxidative stress and normalized liver enzymes in paclitaxel-treated rats.
Co-administration of rutin preserved hepatic structure and improved antioxidant status.
Rutin showed hepatoprotective effects against paclitaxel-induced liver injury.
Keywords : Rutin, Paclitaxel, MDA, GPx, ALT, AST
M. A. Elrahman, “The Possible Protective Role of N-Acetyl Cysteine Against Tamoxifen-Induced Hepatotoxicity in the Adult Female Albino Rats: Biochemical and Histological Study,” Zagazig University Medical Journal, vol. 29, no. 3, pp. 841–851, 2023. [Online]. Available: [https://zumj.journals.ekb.eg](https://zumj.journals.ekb.eg)
S. Biswas, M. Mondal, S. Pakhira, R. Ghosh, P. Samanta, J. Basu, et al., “Attenuation of Paclitaxel-Induced Toxicities by Polyphenolic Natural Compound Rutin Through Inhibition of Apoptosis and Activation of NRF2/ARE Signaling Pathways,” Food and Chemical Toxicology, vol. 200, p. 115408, 2025. doi: 10.1016/j.fct.2025.115408
A. Ganeshpurkar and A. K. Saluja, “The Pharmacological Potential of Rutin,” Saudi Pharmaceutical Journal, vol. 25, no. 2, pp. 149–164, 2017. doi: 10.1016/j.jsps.2016.04.025
J. H. Hoofnagle and E. S. Björnsson, “Drug-Induced Liver Injury – Types and Phenotypes,” The New England Journal of Medicine, vol. 381, no. 3, pp. 264–273, 2019. doi: 10.1056/NEJMra1816149
A. Enogieru, W. Haylett, D. Hiss, S. Bardien, and O. Ekpo, “Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders,” Oxidative Medicine and Cellular Longevity, vol. 2018, Article ID 6245852, pp. 1–17, 2018. doi: 10.1155/2018/6245852
A. Mohammad Humayoon and W. A. Wasim, “Rutin as a Natural Antioxidant and Anti-Diabetic Agent: Mechanisms and Potential Applications in Chronic Disease Management,” Australian Herbal Insight, vol. 8, no. 1, 2025.
Y. A. Ali, H. A. Soliman, M. Abdel-Gabbar, N. A. Ahmed, K. A. A. Attia, F. M. Shalaby, et al., “Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities,” Evidence-Based Complementary and Alternative Medicine, vol. 2023, Article ID 2738351, pp. 1–13, 2023. doi: 10.1155/2023/2738351
S.-S. Choi, H.-R. Park, and K.-A. Lee, “A Comparative Study of Rutin and Rutin Glycoside: Antioxidant Activity, Anti-Inflammatory Effect, Effect on Platelet Aggregation and Blood Coagulation,” Antioxidants, vol. 10, no. 11, p. 1696, 2021. doi: 10.3390/antiox10111696
B. Pravin, V. Nanaware, A. B. Ashwini, G. F. Wondmie, Y. A. B. Jardan, and M. Bourhia, “Assessing the Antioxidant Properties of Naringin and Rutin and Investigating Their Oxidative DNA Damage Effects in Breast Cancer,” Scientific Reports, vol. 14, no. 1, p. 15314, 2024. doi: 10.1038/s41598-024-50913-5
H. Erkan, A. Bozkurt, K. Ercument, A. Erdogan, M. A. G. Mehmet, and H. Suleyman, et al., “Effect of Rutin on Oxidative and Proinflammatory Damage Induced by Cisplatin in Blood Serum, Ureter, Bladder and Urethra in Rats,” Biotechnology & Biotechnological Equipment, vol. 34, no. 1, pp. 171–181, 2020. doi: 10.1080/13102818.2019.1708820
H. M. Ibrahim, F. N. Nadheerah, and H. S. Falah, “The Study on Antioxidant and Anti-Inflammatory Effects of Sodium Copper Chlorophyllin in Male Rats Receiving Indomethacin,” Academia Open, vol. 9, no. 2, 2024. doi: 10.21070/acopen.2024.9.2
D. Shanmugasundaram and J. M. Roza, “Assessment of Anti-Inflammatory and Antioxidant Activity of Quercetin–Rutin Blend (SophorOx) – An In Vitro Cell-Based Assay,” Journal of Complementary and Integrative Medicine, vol. 19, no. 3, pp. 637–644, 2022. doi: 10.1515/jcim-2021-0393
D. A. Madkour, M. Ahmed, A. F. Elkirdasy, S. H. Orabi, and A. A. Mousa, “Rutin: Chemical Properties, Pharmacokinetic Properties and Biological Activities,” Matrouh Journal of Veterinary Medicine, vol. 4, no. 1, pp. 26–34, 2024.
M. M. Anwar and I. M. I. Laila, “The Ameliorating Effect of Rutin on Hepatotoxicity and Inflammation Induced by the Daily Administration of Vortioxetine in Rats,” BMC Complementary Medicine and Therapies, vol. 24, no. 1, p. 153, 2024. doi: 10.1186/s12906-024-04034-8
H. Yang, L. Shen, Y. Yang, and X. Li, “Paclitaxel-Induced Hepatotoxicity in Ovarian Cancer Patients: A Case Report,” Journal of Investigative Medicine High Impact Case Reports, vol. 12, pp. 1–4, 2024. doi: 10.1177/23247096241281603
F. M. Gür, I. Aktaş, S. Bilgiç, and M. Pekince, “Misoprostol Alleviates Paclitaxel-Induced Liver Damage Through Its Antioxidant and Anti-Apoptotic Effects,” Molecular & Cellular Toxicology, vol. 18, no. 3, pp. 393–400, 2022. doi: 10.1007/s13273-022-00245-z