TY  - JOUR
T1  - Paklitaksel Uygulanmış Farelerde Karaciğer, Böbrek ve Kalp Dokularının Histopatolojik Olarak İncelenmesi
TT  - Histopathological Investigation of Liver, Kidney and Heart Tissues in Paclitaxel Treated Mice
AU  - Korkmaz, Oya
AU  - Küçükgünay, Sadık
AU  - Öztürk, Ali Erdem
AU  - Tozak Yıldız, Halime
AU  - Bucak, Mustafa Numan
PY  - 2025
DA  - December
Y2  - 2025
DO  - 10.30607/kvj.1655073
JF  - Kocatepe Veterinary Journal
JO  - kvj
PB  - Afyon Kocatepe Üniversitesi
WT  - DergiPark
SN  - 1308-1594
SP  - 393
EP  - 404
VL  - 18
IS  - 4
LA  - tr
AB  - Paklitaksel (PTS), çeşitli kanser türleri için yaygın olarak kullanılan bir kemoterapi ilacıdır, ancak genellikle birden fazla organ sisteminde önemli toksisiteye neden olur. Bu çalışmada, deneysel bir hayvan modelinde karaciğer, böbrek ve kalp üzerine PTS’nin zararlı etkilerinin ortaya konulması amaçlandı. Çalışmaya 8-10 haftalık erkek Balb/c fareler dahil edildi. Fareler, kontrol (n:5) ve PTS (n:5) olmak üzere iki gruba ayrıldı. 1., 3. ve 5. günlerde intraperitoneal olarak kontrol grubu farelerine serum fizyolojik, PTS grubu farelerine ise 2 mg/kg PTS uygulandı. Hayvanlar, 7. gün sakrifiye edilerek karaciğer, böbrek ve kalp dokuları toplandı ve histopatolojik incelemeler (Hematoksilen Eozin ve Masson Trikrom boyamalar) yapıldı. Kontrol grubunun karaciğer dokusu normal bir histolojik görünüm gösterirken, PTS grubunda apoptotik hücre artışı, konjesyon, sinüzoidal dilatasyon, epitelyal vakuolizasyon, santral vende genişleme ve mononükleer hücre infiltrasyonu gibi belirgin hasarlar gözlemlendi (p<0,001). PTS grubunda böbrek dokusunda tübüllerde ve renal korpüsküllerde atrofi, fırçamsı kenar kaybı, tübüler dilatasyon, interstisyel ödem ve vasküler konjesyon gözlemlendi (p<0,001). PTS grubunda kalp dokusunda miyokardiyal nekroz, liflerin anormal düzenlenmesi, ödem ve mononükleer hücre infiltrasyonu artışı gözlemlendi. Bulgularımız, PTS’nin karaciğer, böbrek ve kalp üzerinde zarar verici potansiyele sahip olduğunu işaret etmektedir.
KW  - Böbrek
KW  - Kalp
KW  - Karaciğer
KW  - Paklitaksel
N2  - Paclitaxel (PTS) is a widely used chemotherapy drug for various types of cancer, but it often causes significant toxicity in multiple organ systems. The aim of this study was to investigate the deleterious effects of PTS on liver, kidney and heart in an experimental animal model. Male Balb/c mice aged 8-10 weeks were included in the study. Mice were divided into two groups as control (n:5) and PTS (n:5). On the 1st, 3rd and 5th days, saline was administered intraperitoneally to control group mice and 2 mg/kg PTS to PTS group mice. Animals were sacrificed on day 7 and liver, kidney and heart tissues were collected and histopathological examinations (Hematoxylin Eosin and Masson Trichrome staining) were performed. While the liver tissue of the control group showed a normal histological appearance, marked damage such as apoptotic cell increase, congestion, sinusoidal dilatation, epithelial vacuolisation, central vein dilatation and mononuclear cell infiltration were observed in the PTS group (p<0.001). In the PTS group, atrophy of tubules and renal corpuscles, loss of brushy edge, tubular dilatation, interstitial oedema and vascular congestion were observed (p<0.001). Myocardial necrosis, abnormal arrangement of fibres, oedema and increased mononuclear cell infiltration were observed in cardiac tissue in the PTS group. Our findings indicate that PTS has a damaging potential on liver, kidney and heart.
CR  - Akbarali, H. I., Muchhala, K. H., Jessup, D. K., & Cheatham, S. (2022). Chemotherapy induced gastrointestinal toxicities. Advances in cancer research, 155, 131–166. https://doi.org/10.1016/bs.acr.2022.02.007
CR  - Aktaş, İ., Gur, F. M., & Bilgiç, S. (2024). Protective effect of misoprostol against paclitaxel-induced cardiac damage in rats. Prostaglandins & Other Lipid Mediators, 171, 106813 https://doi.org/10.1016/j.prostaglandins.2024.106813
CR  - Alexandre, J., Hu, Y., Lu, W., Pelicano, H., & Huang, P. (2007). Novel action of paclitaxel against cancer cells: bystander effect mediated by reactive oxygen species. Cancer research, 67(8), 3512–3517. https://doi.org/10.1158/0008-5472.CAN-06-3914
CR  - Ali, Y. A., Ahmed, O. M., Soliman, H. A., Abdel-Gabbar, M., Al-Dossari, M., El-Gawaad, N. S. A., El-Nahass, E. S., & Ahmed, N. A. (2023). Rutin and Hesperidin Alleviate Paclitaxel-Induced Nephrocardiotoxicity in Wistar Rats via Suppressing the Oxidative Stress and Enhancing the Antioxidant Defense Mechanisms. Evidence-based complementary and alternative medicine: eCAM, 2023, 5068304. https://doi.org/10.1155/2023/5068304
CR  - Awosika, A. O., Farrar, M. C., & Jacobs, T. F. (2023). Paclitaxel. In StatPearls. StatPearls Publishing.
CR  - Banerjee, S., Giannone, G., Clamp, A. R., Ennis, D. P., Glasspool, R. M., Herbertson, R., Krell, J., Riisnaes, R., Mirza, H. B., Cheng, Z., McDermott, J., Green, C., Kristeleit, R. S., George, A., Gourley, C., Lewsley, L. A., Rai, D., Banerji, U., Hinsley, S., & McNeish, I. A. (2023). Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma: The OCTOPUS Multicenter, Phase 2, Randomized Clinical Trial. JAMA oncology, 9(5), 675–682. https://doi.org/10.1001/jamaoncol.2022.7966
CR  - Biswas, S., Mondal, M., Pakhira, S., Ghosh, R., Samanta, P., Basu, J., Bhowmik, A., Hajra, S., & Saha, P. (2025). 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: an international journal published for the British Industrial Biological Research Association, 200, 115408. https://doi.org/10.1016/j.fct.2025.115408
CR  - Camilli, M., Cipolla, C. M., Dent, S., Minotti, G., & Cardinale, D. M. (2024). Anthracycline Cardiotoxicity in Adult Cancer Patients: JACC: CardioOncology State-of-the-Art Review. JACC. CardioOncology, 6(5), 655–677. https://doi.org/10.1016/j.jaccao.2024.07.016
CR  - Chavez, J. D., Keller, A., Zhou, B., Tian, R., & Bruce, J. E. (2019). Cellular Interactome Dynamics during Paclitaxel Treatment. Cell reports, 29(8), 2371–2383.e5. https://doi.org/10.1016/j.celrep.2019.10.063
CR  - Chen, C., Xie, D., Gewirtz, D. A., & Li, N. (2022). Nephrotoxicity in cancer treatment: An update. Advances in cancer research, 155, 77–129. https://doi.org/10.1016/bs.acr.2022.03.005
CR  - Chen, T. S., Wang, X. P., Sun, L., Wang, L. X., Xing, D., & Mok, M. (2008). Taxol induces caspase-independent cytoplasmic vacuolization and cell death through endoplasmic reticulum (ER) swelling in ASTC-a-1 cells. Cancer letters, 270(1), 164–172. https://doi.org/10.1016/j.canlet.2008.05.008
CR  - Chen, Y. T., Sun, C. K., Lin, Y. C., Chang, L. T., Chen, Y. L., Tsai, T. H., Chung, S. Y., Chua, S., Kao, Y. H., Yen, C. H., Shao, P. L., Chang, K. C., Leu, S., & Yip, H. K. (2011). Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. Journal of translational medicine, 9, 51. https://doi.org/10.1186/1479-5876-9-51
CR  - Choi, Y., Kim, S. A., Jung, H., Kim, E., Kim, Y. K., Kim, S., Kim, J., Lee, Y., Jo, M. K., Woo, J., Cho, Y., Lee, D., Choi, H., Jeong, C., Nam, G. H., Kwon, M., & Kim, I. S. (2024). Novel insights into paclitaxel's role on tumor-associated macrophages in enhancing PD-1 blockade in breast cancer treatment. Journal for immunotherapy of cancer, 12(7), e008864. https://doi.org/10.1136/jitc-2024-008864
CR  - Chong, E. G., Lee, E. H., Sail, R., Denham, L., Nagaraj, G., & Hsueh, C. T. (2021). Anthracycline-induced cardiotoxicity: A case report and review of literature. World journal of cardiology, 13(1), 28–37. https://doi.org/10.4330/wjc.v13.i1.28
CR  - da Costa, R., Passos, G. F., Quintão, N. L. M., Fernandes, E. S., Maia, J. R. L. C. B., Campos, M. M., & Calixto, J. B. (2020). Taxane-induced neurotoxicity: Pathophysiology and therapeutic perspectives. British journal of pharmacology, 177(14), 3127–3146. https://doi.org/10.1111/bph.15086
CR  - Du, J., Zong, L., Li, M., Yu, K., Qiao, Y., Yuan, Q., & Pu, X. (2022). Two-Pronged Anti-Tumor Therapy by a New Polymer-Paclitaxel Conjugate Micelle with an Anti-Multidrug Resistance Effect. International journal of nanomedicine, 17, 1323–1341. https://doi.org/10.2147/IJN.S348598
CR  - Eşrefoğlu, M., Gül, M., Ates, B., Batçioğlu, K., & Selimoğlu, M. A. (2006). Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats. World journal of gastroenterology, 12(2), 259–264. https://doi.org/10.3748/wjg.v12.i2.259
CR  - Fairlie, W. D., & Lee, E. F. (2021). Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers. Biochemical Society transactions, 49(5), 2397–2410. https://doi.org/10.1042/BST20210750
CR  - Fanous, H., & Liu, Y. (2022). Carboplatın-Paclıtaxel Induced Acute Multı-Vessel Coronary Thrombosıs. Journal of the American College of Cardiology, 79(9_Supplement), 2659-2659.
CR  - Fu, Q., Sun, X., Lustburg, M. B., Sparreboom, A., & Hu, S. (2019). Predicting Paclitaxel Disposition in Humans With Whole-Body Physiologically-Based Pharmacokinetic Modeling. CPT: pharmacometrics & systems pharmacology, 8(12), 931–939. https://doi.org/10.1002/psp4.12472
CR  - Gagandeep, S., Novikoff, P. M., Ott, M., & Gupta, S. (1999). Paclitaxel shows cytotoxic activity in human hepatocellular carcinoma cell lines. Cancer letters, 136(1), 109–118. https://doi.org/10.1016/s0304-3835(98)00388-7
CR  - Gür, F. M., & Aktaş, İ. (2022). Silymarin protects kidneys from paclitaxel-induced nephrotoxicity.
CR  - Gür, F. M., & Bilgiç, S. (2023). Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel. Tissue & cell, 83, 102158. https://doi.org/10.1016/j.tice.2023.102158
CR  - Hertz, D. L., Joerger, M., Bang, Y. J., Mathijssen, R. H., Zhou, C., Zhang, L., Gandara, D., Stahl, M., Monk, B. J., Jaehde, U., & Beumer, J. H. (2024). Paclitaxel therapeutic drug monitoring- International association of therapeutic drug monitoring and clinical toxicology recommendations. European journal of cancer (Oxford, England: 1990), 202, 114024. https://doi.org/10.1016/j.ejca.2024.114024
CR  - Hu, Y., Manasrah, B. K., McGregor, S. M., Lera, R. F., Norman, R. X., Tucker, J. B., Scribano, C. M., Yan, R. E., Humayun, M., Wisinski, K. B., Tevaarwerk, A. J., O'Regan, R. M., Wilke, L. G., Weaver, B. A., Beebe, D. J., Jin, N., & Burkard, M. E. (2021). Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS-STING Signaling in Triple-Negative Breast Cancer. Molecular cancer therapeutics, 20(12), 2553–2567. https://doi.org/10.1158/1535-7163.MCT-21-0195
CR  - Kara, A., & Ozkanlar, S. (2023). Blockade of P2X7 receptor-mediated purinergic signaling with A438079 protects against LPS-induced liver injury in rats. Journal of biochemical and molecular toxicology, 37(10), e23443. https://doi.org/10.1002/jbt.23443
CR  - Khing, T. M., Choi, W. S., Kim, D. M., Po, W. W., Thein, W., Shin, C. Y., & Sohn, U. D. (2021). The effect of paclitaxel on apoptosis, autophagy and mitotic catastrophe in AGS cells. Scientific reports, 11(1), 23490. https://doi.org/10.1038/s41598-021-02503-9
CR  - Kim, G. E., Ibrahim, A. R., Shalatouni, D., Abouzeid, N. H., & Othman, F. (2024a). Paclitaxel-induced acute myocardial infarction: a case report and literature review. BMC cardiovascular disorders, 24(1), 167. https://doi.org/10.1186/s12872-024-03814-1
CR  - Kim, J. S., Suh, K. J., Lee, D. W., Woo, G. U., Kim, M., Kim, S. H., Ryu, H. S., Lee, K. H., Kim, T. Y., Han, S. W., Park, S. Y., Park, I. A., Kim, J. H., & Im, S. A. (2022). A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer. Cancer research and treatment, 54(2), 488–496. https://doi.org/10.4143/crt.2021.394
CR  - Kim, R., Kin, T., & Beck, W. T. (2024b). Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy. Cancers, 16(5), 984. https://doi.org/10.3390/cancers16050984
CR  - Lee, C. C., Lee, R. P., Subeq, Y. M., Lee, C. J., Chen, T. M., & Hsu, B. G. (2009). Fluvastatin attenuates severe hemorrhagic shock-induced organ damage in rats. Resuscitation, 80(3), 372–378. https://doi.org/10.1016/j.resuscitation.2008.12.003
CR  - Li, S. F., Ouyang, X., Feng, S., Wan, M. Z., Zhou, K. N., Wen, B. Y., Yin, Y. Z., Yi, H., & Chen, X. Y. (2025). Oncohepatology: Navigating liver injury in the era of modern cancer therapy. World journal of hepatology, 17(6), 106932. https://doi.org/10.4254/wjh.v17.i6.106932
CR  - Lyrio, R. M. D. C., Rocha, B. R. A., Corrêa, A. L. R. M., Mascarenhas, M. G. S., Santos, F. L., Maia, R. D. H., Segundo, L. B., de Almeida, P. A. A., Moreira, C. M. O., & Sassi, R. H. (2024). Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches. Frontiers in nephrology, 4, 1436896. https://doi.org/10.3389/fneph.2024.1436896
CR  - Merouani, A., Davidson, S. A., & Schrier, R. W. (1997). Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone. American journal of nephrology, 17(1), 53–58. https://doi.org/10.1159/000169072
CR  - Park, S. J., Wu, C. H., Gordon, J. D., Zhong, X., Emami, A., & Safa, A. R. (2004). Taxol induces caspase-10-dependent apoptosis. The Journal of biological chemistry, 279(49), 51057–51067. https://doi.org/10.1074/jbc.M406543200
CR  - Prakash, S., Radha, Kumar, M., Kumari, N., Thakur, M., Rathour, S., Pundir, A., Sharma, A. K., Bangar, S. P., Dhumal, S., Singh, S., Thiyagarajan, A., Sharma, A., Sharma, M., Changan, S., Sasi, M., Senapathy, M., Pradhan, P. C., Garg, N. K., Ilakiya, T., Nitin, M., Abdel-Daim, M. M., Puri, S., Natta, S., Dey, A., Amarowicz, R., & Mekhemar, M. (2021). Plant-Based Antioxidant Extracts and Compounds in the Management of Oral Cancer. Antioxidants (Basel, Switzerland), 10(9), 1358. https://doi.org/10.3390/antiox10091358
CR  - Rabah S. O. (2010). Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma. Saudi journal of biological sciences, 17(2), 105–114. https://doi.org/10.1016/j.sjbs.2010.02.003
CR  - Salahshoor, M. R., Vahabi, A., Roshankhah, S., Darehdori, A. S., & Jalili, C. (2018). The Effects of Thymoquinone Against Morphine-induced Damages on Male Mice Liver. International journal of preventive medicine, 9, 8. https://doi.org/10.4103/ijpvm.IJPVM_144_16
CR  - Satheesh, C. T., Taran, R., Singh, J. K., Shrivastav, S. P., Vithalani, N. K., Mukherjee, K. K., Nagarkar, R. V., Maksud, T., Mehta, A. O., Srinivasan, K., Vikranth, M., Sonawane, S. R., Ahmad, A., Sheikh, S., Ali, S. M., Patel, R., Paithankar, M., Patel, L., Rajani, A., Bunger, D., Chaturvedi, A., & Ahmad, I. (2024). Treatment with nanosomal paclitaxel lipid suspension versus conventional paclitaxel in metastatic breast cancer patients - a multicenter, randomized, comparative, phase II/III clinical study. Therapeutic advances in medical oncology, 16, 17588359241236442. https://doi.org/10.1177/17588359241236442
CR  - Schmidt, M., Vernooij, R., van Nuland, M., Smeijsters, E., Devriese, L., Mohammad, N. H., Hermens, T., Stammers, J., Swart, C., Egberts, T., Haitjema, S., & Lammers, L. (2024). Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival. BMC cancer, 24(1), 1553. https://doi.org/10.1186/s12885-024-13330-2
CR  - Shen, Y., Zhang, F. Q., & Wei, X. (2014). Truncated monocyte chemoattractant protein-1 can alleviate cardiac injury in mice with viral myocarditis via infiltration of mononuclear cells. Microbiology and immunology, 58(3), 195–201. https://doi.org/10.1111/1348-0421.12130
CR  - Sommer, K., Peters, S. O., Robins, I. H., Raap, M., Wiedemann, G. J., Remmert, S., Sieg, P., Bittner, C., & Feyerabend, T. (2001). A preclinical model for experimental chemotherapy of human head and neck cancer. International journal of oncology, 18(6), 1145–1149. https://doi.org/10.3892/ijo.18.6.1145
CR  - Tan, T., Li, S., Hu, W., Yue, T., Zeng, Q., Zeng, X., Chen, X., Zhao, X., & Xiao, T. (2023). Efficacy and safety of nab-paclitaxel plus platinum in non-small cell lung cancer: a meta-analysis. Frontiers in medicine, 10, 1139248. https://doi.org/10.3389/fmed.2023.1139248.
CR  - Wang, X., Gigant, B., Zheng, X., & Chen, Q. (2023). Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies. MedComm–Oncology, 2(3), e46.
CR  - World Health Organization. (2017). Cancer prevention and control in the context of an integrated approach. World Health Assembly Resolution WHA70, 12. (https://apps.who.int/gb/ebwha/pdf_files/EB140/B140_31-en.pdf).
CR  - Yang, H., Shen, L., Yang, Y., & Li, X. (2024). Paclitaxel-Induced Hepatotoxicity in Ovarian Cancer Patients: A Case Report. Journal of investigative medicine high impact case reports, 12, 23247096241281603. https://doi.org/10.1177/23247096241281603
CR  - Yang, X., Tian, X., Zhao, P., Wang, Z., & Sun, X. (2023). Paclitaxel inhibits hepatocellular carcinoma tumorigenesis by regulating the circ_0005785/miR-640/GSK3β. Cell biology international, 47(7), 1170–1182. https://doi.org/10.1002/cbin.11906
CR  - Zhang, D., Li, Y., Liu, Y., Xiang, X., & Dong, Z. (2013). Paclitaxel ameliorates lipopolysaccharide-induced kidney injury by binding myeloid differentiation protein-2 to block Toll-like receptor 4-mediated nuclear factor-κB activation and cytokine production. The Journal of pharmacology and experimental therapeutics, 345(1), 69–75. https://doi.org/10.1124/jpet.112.202481
UR  - https://doi.org/10.30607/kvj.1655073
L1  - https://dergipark.org.tr/tr/download/article-file/4678372
ER  -