Nephrotoxicity of Cyclophosphamide on Female Golden Hamster: Histopathological Study.
DOI:
https://doi.org/10.37376/ljst.v14i1.7187Abstract
Cyclophosphamide is considered one of the most effective alkylating anticancer drugs used worldwide. But it is also acknowledged for its damaging side effects including nephrotoxicity, hepatotoxicity, immunotoxicity, and mutagenicity. This study was to investigate the histopathological changes induced by intraperitoneal injection of different doses of cyclophosphamide on the kidney tissue in female golden hamsters (Mesocricetus auratus). In this experimental study, 27 female golden hamsters were divided into three groups, control, therapeutic, and toxic dose groups. Animals in the control group were injected with normal saline, while those in the therapeutic, and toxic groups were injected with cyclophosphamide at doses of 100 and 200 mg/kg body weight respectively. The dosing was carried out on days 1, 3, and 5. Then on the seventh day, animals were humanely sacrificed. The kidney was maintained in formalin for histological examination. Histological examination of kidney tissue obtained from the animals treated with 100 mg/kg body weight cyclophosphamide (therapeutic dose) showed mild congestion in the glomerular capillaries and mild swelling of lining epithelial of some tubules. A significant histological alteration was observed at the toxic dose of 200 mg/kg body weight cyclophosphamide, were tubular necrosis and damage of renal glomeruli, this shows dose-dependent effects of the drug. The current study showed that the acute toxicity of renal tissue in female golden hamsters could be induced by the therapeutic or toxic doses of cyclophosphamide. Histopathological alterations were observed in the kidney tissue.
Downloads
References
Abraham, P., Indirani, K., and Sugumar, E. (2007) ‘Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats’, Explained Toxicology Pathology, 59, pp.143-149.
Alabi, Q., Akomolafe, R., Omole, J., Aturamu, A., Ige, M., Kayode, O., Kajewole Alabi, D. (2021) ‘Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats’, BMC Complement Med Ther., 21, pp. 274.
Alashger, A., Amer, A. and Benhasouna, A. (2021) ‘Histopathological Study of Carcinoma Cervix through Reviewing of Female Genital Tract Cancer Cases of Pathology Archive, Benghazi University from (2002-2011)’, SJUOB., 34(2), pp. 217 -225.
Begum, N.A., Dewan, Z.F., Nahar, N., & Mamun, M.I.R. (2006) ‘Effect of n-Hexane extract of Nigella sativa on gentamicin induced nephrotoxicity in rats’, Bangladesh J. Pharmacol., 1, pp.16-20.
Cengiz, M. (2018) ‘Boric acid protects against cyclophosphamide-induced oxidative stress and renal damage in rats’, Cellular and Molecular Biology, 64(12), pp.11-14.
Choudhury, D., Ahmed, Z. (2006) ‘Drug-associated renal dysfunction and injury’, Nat. Clin. Pract. Neph., 2(2), pp. 80-91.
Cuce, G., Esen, H. H., Koc, T., Canbaz, H. T., Limandal, C., Kalkan, S., and Gurbilek, M. (2016) ‘Vitamin E partially ameliorates cyclophosphamide-induced nephrotoxicity in rats’, Progress in nutrition, 18(2), pp. 140-145.
Dobrek, Ł., Skowron, B., Baranowska, A., Ciesielczyk, K., Kopańska, M., and Thor, P. (2017) ‘Nephrotoxicity of a single dose of cyclophosphamide and ifosfamide in rats’, Acta Poloniae Pharmaceutica. Drug Research, 74(5), pp. 1579-1589
Estakhri, R., Hajipour, B., Majidi, H., & Soleimani, H. (2013) ‘Vitamin E ameliorates cyclophosphamide-induced nephrotoxicity’, Life Science, J;10(6s) pp. 308-13.
Fraiser, L. H., Kanekal, S., Kehrer, J. P. (1991) ‘Cyclophosphamide Toxicity characterizing and avoiding the problem’, Drugs, 42(5) pp. 781-95. DOI: 10.2165/00003495-199142050-00005.
Ghosh, S., Ghosh, D., Chattopadhyay, S., and Debnath, J. (1999) ‘Effect of ascorbic acid supplementation on liver and kidney toxicity in cyclophosphamide -treated female albino rats’, J. Toxicol. Science, 24, pp. 141–144.
Hamzeh, M., Talebpour, A. F., Yaghubi, B. S., and Hosseinimehr, S. J. (2018) ‘Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice’, Marmara Pharm J., 22 (2), pp. 180- 189.
Joy, J., and Nair, C. (2008) ‘Amelioration of cisplatin-induced nephrotoxicity in Swiss albino mice by Rubia cordifolia extract’, J Can Res Ther., 4(3), pp. 111-115.
Kalantari, H., Jalali, M., Jalali, A., Salimi, A., Alhalvachi, F., and Varga, B. (2011) ‘Protective effect of Cassia fistula fruit extract on bromobenzene- induced nephrotoxicity in mice’, Hum Exp Toxicol., 30(10), pp. 1710-5.
Kern, J.C., and Kehrer, J.P. (2002) ‘Acrolein-induced cell death: a cas¬pase influenced decision between apoptosis and oncosis/necrosis’, Chem. Biol. Interact., 139, pp. 79–95.
Koss, L.G., and Lavin, P. (1970) ‘Effects of a Single dose of cyclophosphamide on various organs in the rat. II. Response of urinary bladder epithelium according to strain and sex’, J Natl Cancer Inst., 44(5), pp. 1195-200.
Małyszko, J., Kozlowski, L., and Kozłowska, K., (2017) ‘Cancer and the kidney: dangereoux liasons or price paid for the progress in medicine’, Oncotarget., 8, pp. 66601-66619.
McDonald, G., Slattery, J., Bouvier, M., Red, S., Batchelder, A. L., and Kalhorn, T. F. (2003) ‘Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation’, Blood, 101(5), pp. 2043 -2048.
Merwid-L, A.; Ziółkowski, P., Szandruk-Bender, M., Matuszewska, A., Szel, A., Trocha, M. (2021) ‘Effect of a Low Dose of Carvedilol on Cyclophosphamide-Induced Urinary Toxicity in Rats’, A Comparison with Mesna. Pharmaceuticals, 14, pp. 1237.
Nandini, B., Sneha, G. K., Supriya, P., and Vidya, M. (2018) ‘Toxic Effects of different Doses of Cyclophosphamide on Liver and Kidney Tissue in Swiss Albino Mice: A Histopathological Study’, Ethiop J Science, 28(6), pp. 711.
Paget, G. E., and Barnes, J. M. (1964) Toxicity Tests. In: Laurence, D.R., and Bacharach, A.L., Eds., Evaluation of Drug Activities, Academic Press, Massachusetts, pp. 1:135.
Que, L., He, L., and Yu, C. (2016) ‘Activation of Nrf2-ARE signaling mitigates cyclophosphamide-induced myelosuppression’, Toxicol. Lett., 262, pp. 17–26.
Sadeghi, A., Kalantar, M., Molavinia, S., Houshmand, G., Bahadoram, M., and Esmaeilizadeh, M., (2017) ‘Ameliorative effects of hydroalcoholic extract of Lavandula officinalis L. on cyclophosphamide-induced nephrotoxicity in mice’, J Nephropathol., 6(4), pp. 324-332.
Said, E., Elkashef, W.F., and Abdelaziz, R. R. (2016) ‘Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity’, Can. J. Physiology Pharmacology, 94, pp. 347–358.
Sakr, S. A., and Abdel-Samie, H. A. (2016) ‘Effect of Ginko Biloba extract on cyclophosphamide-induced nephrotoxicity and oxidative stress in albino rats’, Canadian J. Pure Applied Science, 10(2), pp. 3835-3845.
Sakr S., and El-messady, F. (2017) ‘Cyclophosphamide Induced Histological and Immunohistochemical alterations in Kidney of Albino Rats: The Ameliorative Effect of Fennel Oil’, International Journal of Sciences, 6(8), pp. 78-87.
Schnellmann, R.G. (2008) Toxic Responses of the Kidney.' Casarett and Doull’s Toxicology, the basic science of poisons 1., 7th ed. New York: McGraw-Hill, pp. 583-7.
Senthilkumar, S., Devaki, T., Manohar, B. M., and Babu, M. S. (2006) ‘Effect of squalene on cyclophosphamide-induced toxicity’, Clinical Chim. Acta., 364 pp. 335–342.
Sugumar, E., Kanakasabapathy, I., and Abraham, P. (2007) ‘Normal plasma creatinine level despite histological evidence of damage and increased oxidative stress in the kidneys of cyclophosphamide treated rats’, Clin. Chim. Acta., 376, pp. 244–245.
Talar-Williams, C., Hijazi, Y. M., Walther, M. M., Linehan, W. M., Hallahan, C. W., and Lubensky, I. (1996) ‘Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis’, Ann Intern Med., 124, pp. 477-484.
Tatiane Y., Nakamura K., Lucimara A., Natália A., and Maria. J. (2009) ‘Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice’, Brazilian Journal of Pharmaceutical Sciences, 45(2), pp. 313-319.
Zarei, M., and Shivanandappa, T. (2016) ‘Neuroprotective effect of De¬calepis hamiltoni on cyclophosphamide-induced oxidative stress in the mouse brain’, J. Basic Clin. Physiol. Pharmacol., 27, pp. 341–348.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Libyan Journal of Science &Technology
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
