Histopathological Studies on the Effect of Taurine Against Etoposide-Induced Acute Liver and Kidney Toxicity in Female Albino Rats


  • Arwa Salam Mohammed Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq http://orcid.org/0000-0002-9838-6591
  • Ansam N. Al-Hassani Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq




Etoposide, Taurine, Liver, Kidney, Toxicity


Etoposide (ETP) is a topoisomerase Ⅱ (TOP Ⅱ) inhibitor and one of the leading chemotherapeutic drugs for treating a wide variety of tumors. However, ETP induced hepatotoxicity and nephrotoxicity limits its clinical use. This study aims to investigate the protective potential of taurine (Tau) to mitigated histopathological changes in the liver and kidneys of female albino rats treated with ETP. A total of 18 female rats were divided into three groups; control group, ETP-exposed group received intraperitoneal injection of ETP on the first 3 days of the study for a total cumulative dose of 44 mg/kg to induce hepatotoxicity and nephrotoxicity, ETP + Tau group received ETP as stated previously with 400 mg/kg/day of Tau via oral gavage for 15 days. Sections from the liver and kidney were evaluated under light microscope and ETP-exposed group revealed vascular congestion, chronic inflammatory cell infiltration predominantly lymphocytes, edema, vacuolar degeneration, atypical cells, pyknosis, and necrosis while liver and kidney sections of rats treated with combination of ETP + Tau group exhibited marked alleviation of the histopathological damage. The study concludes that treatment with ETP induced marked structural damages in the liver and kidney and such morphological damages are effectively diminished by administering Tau.


Download data is not yet available.


Alam, S.S., Hafiz, N.A. & Abd El-Rahim, A.H. (2011). Protective role of taurine against genotoxic damage in mice treated with methotrexate and tamoxfine. Environ. Toxicol. Pharmacol, 31(1), 143–152.
Alhumaidha, K.A., Saleh, D.O., Abd El Fattah, M.A., El-Eraky, W.I. & Moawad, H. (2016). Cardiorenal protective effect of taurine against cyclophosphamide-induced toxicity in albino rats. Can. J. Physiol. Pharmacol, 94, 131–139.
Almakhatreh, M., Hafez, E., Tousson, E. & Masoud, A. (2019). Biochemical and Molecular Studies on the Role of Rosemary (Rosmarinus officinalis) Extract in Reducing Liver and Kidney Toxicity Due to Etoposide in Male Rats. Asian J. Res. Med. Pharm, 7(4), 1–11.
Baliou, S., Adamaki, M., Ioannou, P., Pappa, A., Panayiotidis, M.I., Spandidos, D.A., Christodoulou, I., Kyriakopoulos, A.M. & Zoumpourlis, V. (2021). Protective role of taurine against oxidative stress (Review). Mol. Med. Rep, 24, 605.
Barış, V.Ö., Gedikli, E., Yersal, N., Müftüoğlu, S. & Erdem, A. (2019). Protective effect of taurine against doxorubicin-induced cardiotoxicity in rats: echocardiographical and histological findings. Amino Acids, 51, 1649–1655.
Barnoud, D., Pinçon, C., Bruno, B., Béné, J., Gautier, S., Lahoche, A., Petitpain, N., Vasseur, M., Barthélémy, C., Décaudin, B., Simon, N. & Odou, P. (2018). Acute kidney injury after high dose etoposide phosphate: A retrospective study in children receiving an allogeneic hematopoetic stem cell transplantation. Pediatr. Blood Cancer, 65(7), e27038.
Bregman, C.L., Buroker, R.A., Hirth, R.S., Crosswell, A.R. & Durham, S.K. (1994). Etoposide- and BMY-40481-Induced Sensory Neuropathy in Mice. Toxicol. Pathol, 22(5), 528–535.
Cavdar, Z., Ural, C., Celik, A., Arslan, S., Terzioglu, G., Ozbal, S., Yildiz, S., Ergur, U.B., Guneli, E., Camsari, T. & Akdogan, G. (2017). Protective effects of taurine against renal ischemia/reperfusion injury in rats by inhibition of gelatinases, MMP-2 and MMP-9, and p38 mitogen-activated protein kinase signaling. Biotech. Histochem. Off. Publ. Biol. Stain Comm, 92(7), 524–535.
Dinçer, S., Ozenirler, S., Oz, E., Akyol, G. & Ozoğul, C. (2002). The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage--a light and electron microscopic study. Amino Acids, 22(4), 417–426.
Doğru-Abbasoğlu, S., Kanbağli, O., Balkan, J., Cevikbaş, U., Aykaç-Toker, G. & Uysal, M. (2001). The protective effect of taurine against thioacetamide hepatotoxicity of rats. Hum. Exp. Toxicol, 20(1), 23–27.
Gökçe, A.B., Eren, B., Sağır, D. & Demirel Yılmaz, B. (2021). A histopathological and stereological study of the effects of acetylsalicylic acid on doxorubicin-induced hepatotoxicity in mice. Biotech. Histochem. Off. Publ. Biol. Stain Comm, 96, 251–256.
Hagar, H.H. (2004). The protective effect of taurine against cyclosporine A-induced oxidative stress and hepatotoxicity in rats. Toxicol. Lett, 151(2), 335–343.
Hernández-Benítez, R., Ramos-Mandujano, G. & Pasantes-Morales, H. (2012). Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells. Stem Cell Res, 9(1), 24–34.
Ibrahim Fouad, G. & Ahmed, K.A. (2021). Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat’s Brain. Neurochem. Res, 46, 3247–3263.
Jakaria, Md., Azam, S., Haque, Md.E., Jo, S.-H., Uddin, Md.S., Kim, I.-S. & Choi, D.-K. (2019). Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol, 24, 101223.
Kamble, P., Kulkarni, S. & Bhiwgade, D.A. (2013). Ultrastructural and antioxidant studies of etoposide treated kidney of rat. J. Cancer Sci. Ther, 5(4), 137–141.
Kim, Y.-S., Sung, S.-H., Tang, Y., Choi, E.-J., Choi, Y.-J., Hwang, Y.J., Park, P.-J. & Kim, E.-K. (2017). Protective Effect of Taurine on Mice with Doxorubicin-induced Acute Kidney Injury. Adv. Exp. Med. Biol, 975 Pt 2, 1191–1201.
Kluska, M. & Woźniak, K., 2021. Natural Polyphenols as Modulators of Etoposide Anti-Cancer Activity. Int. J. Mol. Sci, 22(12), 6602.
Konecny, F. (2021). Rodent General Anesthesia Suitable for Measurement of Experimental Invasive Hemodynamics. Eur. J. Exp. Biol, 2(4), 33–43.
Kwon, H.-K., Shin, H.-J., Lee, J.-H., Park, S.-H., Kwon, M.-C., Panneerselvam, S., Lee, C.G., Kim, S.G., Kim, J.-H. & Choi, S. (2015). Etoposide Induces Necrosis Through p53-Mediated Antiapoptosis in Human Kidney Proximal Tubule Cells. Toxicol. Sci, 148(1), 204–219.
Lee, C., Leventhal, T.M. & Anugwom, C.M. (2021). L-Asparaginase-Induced Hepatotoxicity Treated Successfully With L-Carnitine and Vitamin B Infusion. Cureus, 13(8).
Małyszko, J., Kozłowska, K., Kozłowski, L. & Małyszko, J. (2017). Nephrotoxicity of anticancer treatment. Nephrol. Dial. Transplant, 32(6), 924–936.
Maor, Y. & Malnick, S. (2013). Liver Injury Induced by Anticancer Chemotherapy and Radiation Therapy. Int. J. Hepatol, e815105.
Meresse, P., Dechaux, E., Monneret, C. & Bertounesque, E. (2004). Etoposide: Discovery and Medicinal Chemistry. Curr. Med. Chem, 11(18), 2443–2466.
Miyazaki, T., Bouscarel, B., Ikegami, T., Honda, A. & Matsuzaki, Y. (2009). The protective effect of taurine against hepatic damage in a model of liver disease and hepatic stellate cells. Adv. Exp. Med. Biol, 643, 293–303.
Mudd, T.W. & Guddati, A.K. (2021). Management of hepatotoxicity of chemotherapy and targeted agents. Am. J. Cancer Res, 11(7), 3461–3474.
Nagai, K., Fukuno, S., Oda, A. & Konishi, H. (2016). Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses. Anticancer. Drugs, 27(1), 17–23.
Nemade, H., Chaudhari, U., Acharya, A., Hescheler, J., Hengstler, J.G., Papadopoulos, S. & Sachinidis, A. (2018). Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch. Toxicol, 92(4), 1507–1524.
Perazella, M.A. (2012). Onco-Nephrology: Renal Toxicities of Chemotherapeutic Agents. Clin. J. Am. Soc. Nephrol, 7(10), 1713–1721.
Rao, G., Pandey, R. & Marathe, A. (2019). Ameliorating effect of whey preparation on Na + -K + -ATPase and oxidative stress in chemotherapy induced rat model for brain toxicity. Biomedicine, 39(3), 405–409.
Rjiba-Touati, K., Amara, I., Bousabbeh, M., Salem, I.B., Azzebi, A., Guedri, Y., Achour, A., Bacha, H. & Abid, S. (2018). Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats. Hum. Exp. Toxicol, 37(8), 848–858.
Saad, S.Y. & Al-Rikabi, A.C. (2002). Protection effects of Taurine supplementation against cisplatin-induced nephrotoxicity in rats. Chemotherapy, 48, 42–48.
Saleh, E.M., El-awady, R.A., Eissa, N.A. & Abdel-Rahman, W.M. (2012). Antagonism between curcumin and the topoisomerase II inhibitor etoposide: a study of DNA damage, cell cycle regulation and death pathways. Cancer Biol. Ther, 13(11), 1058–1071.
Santos, M.L.C., de Brito, B.B., da Silva, F.A.F., Botelho, A.C. dos S., & de Melo, F.F. (2020). Nephrotoxicity in cancer treatment: An overview. World J. Clin. Oncol, 11(4), 190–204.
Shah, Z., Gohar, U.F., Jamshed, I., Mushtaq, A., Mukhtar, H., Zia-UI-Haq, M., Toma, S.I., Manea, R., Moga, M. & Popovici, B. (2021). Podophyllotoxin: History, Recent Advances and Future Prospects. Biomolecules, 11(4), 603.
Shivakumar, P., Rani, M.U., Reddy, A.G. & Anjaneyulu, Y. (2012). A study on the toxic effects of Doxorubicin on the histology of certain organs. Toxicol. Int, 19(3), 241–244.
Thatishetty, A.V., Agresti, N. & O’Brien, C.B. (2013). Chemotherapy-induced hepatotoxicity. Clin. Liver Dis, 17(4), 671–686.
Torri, G.B., Soldatelli, M.D., Luersen, G.F. & Ghezzi, C.L.A. (2021). Imaging of chemotherapy-induced liver toxicity: an illustrated overview. Hepatic Oncol, 8(4).
Tousson, E., Masoud, A., Hafez, E. & Almakhatreh, M. (2019). Protective role of rosemary extract against Etoposide induced liver toxicity, injury and KI67 alterations in rats. J. Biosci. Appl. Res, 5(1), 1–7.
Tran, A., Housset, C., Boboc, B., Tourani, J.-M., Carnot, F. & Berthelot, P. (1991). Etoposide (VP 16-213) induced hepatitis. Report of three cases following standard-dose treatments. J. Hepatol, 12(1), 36–39.
Wenting, L., Ping, L., Haitao, J., Meng, Q. & Xiaofei, R. (2014). Therapeutic effect of taurine against aluminum-induced impairment on learning, memory and brain neurotransmitters in rats. Neurol. Sci, 35, 1579–1584.
Yousef, H.N. & Aboelwafa, H.R. (2017). The potential protective role of taurine against 5-fluorouracil-induced nephrotoxicity in adult male rats. Exp. Toxicol. Pathol, 69(5), 265–274.
Zhang, W., Gou, P., Dupret, J.-M., Chomienne, C. & Rodrigues-Lima, F. (2021). Etoposide, an anticancer drug involved in therapy-related secondary leukemia: Enzymes at play. Transl. Oncol, 14(10), 101169.





Research Articles

How to Cite

Histopathological Studies on the Effect of Taurine Against Etoposide-Induced Acute Liver and Kidney Toxicity in Female Albino Rats. (2022). UKH Journal of Science and Engineering, 6(2), 75-82. https://doi.org/10.25079/ukhjse.v6n2y2022.pp75-82

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 9 10 > >>