Cyclophosphamide (CPA) is a nitrogen mustard alkylating agent from the oxazaphosphorine group. It is used as an anticancer, anti-neoplastic agents and immunosuppressive agent widely used in chemotherapy. Fennel oil is traditionally used as a treatment for different diseases. The present work studied the effect of Fennel oil on CPA-induced nephrotoxicity in albino rats. Male albino rats were divided into 4 groups; gp1; control, gp2: Each rat was orally given Fennel oil (1 ml/kg body weight once a week for six weeks), gp3: animals were each orally treated with CPA at a dose of 15mg/kg body weight once a week for six weeks, gp4: CPA plus Fennel oil treated group. The obtained results showed that CPA induced histopathological alterations in the kidney including intertubular leucocytic infiltrations,congestion of blood vessels, degeneration of renal tubules and atrophy of glomeruli. Immunohistochemical observations revealed increase in expression of PCNA, caspase-3 and α -SMA. In addition, creatinine and urea levels increased in sera of treated rats. Treating rats with CPA and fennel oil caused an improvement in the histological structure of the kidney and decreased PCNA, caspase-3 and α-SMA. Moreover, creatinine and urea values were decreased. In conclusion, fennel oil showed ameliorative effect against nephrotoxicity of CPA due to its antioxidant activity.
Cyclophosphamide, Fennel Oil, Kidney, Histology, , PCNA, α-SMA, Rats
- Rather, A.; Bilal A. Dar, Shahnawaz, Sofi, N.; Bilal A. Bhat, Mushtaq A. and Qurishi, A. (2016). Foeniculum vulgare: a comprehensive review of its traditional use, phytochemistry, pharmacology, and safety Arab. J. Chem.9(2): S1574-S1583
- Delaram, M.; Kheiri, S. and Hodjati, M.R. (2011): Comparing the effects of echinop hora-platyloba, fennel and placebo on pre-menstrual syndrome J. Reprod. Infertil., 12 (3) : 221–226
- Aggarwal, B. B.; Kunnumakkara, A. B.; Harikumar, K. B.; Tharakan, S. T.; Sung, B. and Anand, P. (2008): Potential of spice-derived phytochemicals for cancer prevention. Planta Med. 74(13): 1560-9.
- Ozbek, H.; Uğraş, S.; Dülger, H.; Bayram, I.; Tuncer, I.; Oztürk, G. and Oztürk, A. (2003): Hepatoprotective effect of Foeniculum vulgare essential oil Fitoterapia, 74: 317–319
- Mimica-Dukic, N., B. Bozin, M. Sokovic, B. Mihajlovic and M. Matavulj. (2003): Antimicrobial and antioxidant activities of three Mentha species essential oils. Planta Medica, 69: 413-419.
- Soylu, E. M., Soylu, S., & Kurt, S. (2006). Antimicrobial activities of the essential oils of various plants against tomato late blight disease agent Phytophthorainfestans. Mycopathologia, 161: 119-128.
- Choi, E.M. and Hwag, J.K. (2004): Anti-inflammatory, analgesic and antioxidant activities of the fruit of Foeniculum vulgare . Fitoterapia. 75(6): 557-565
- Takimoto, CH. & Calvo, E. (2005): Principles of oncologic pharmacotherapy. In: Cancer Management: A Multidisciplinary Approach. Medical, Surgical & Radiation Oncology. Pazdur, R.; Coia, LR.; Hoskins WJ & Wagman, LD. (Eds.), pp. 23-43, CMP Healthcare Media, Washington, USA
- Huttunen, K.M.; Raunio, H. and Rautio, J. (2011): Prodrugs--from serendipity to rational design. Pharmacological Reviews 63 (3): 750–71.
- Boddy Av and Yule SM (2000): Metabolism and pharmacokinetics of oxazaphosphorines . Clin Pharmacokinet 38(4) : 291-304
- Kehrer JP, Biswal SS.(2000): The molecular effects of acrolein. Toxicological Sciences. 57:6–15.
- Bernatsky S, Clarke AE.(2008): Ramsey-Goldman R. Cancer in systemic lupus: what drives the risk? Cancer Causes Control CCC. 19(10):1413–1414
- Floyd, J.D.; Nguyen, D.T.; Lobins, R.L.; Bashir, Q.; Doll, D.C. and Perry, M.C. (2005): Cardiotoxicity of cancer therapy. J. Clinical Oncology 23 (30): 7685–96
- Li, F.; Patterson, A.D., Höfer, C.C.; Krausz, K.W.; Gonzalez, F.J. and Idle, J.R.(2010): Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC-ESI-QTOFMS-based metabolomics. Biochem Pharmacol.,80(7):1063-1074.
- Sakr, S.A. and Hany A. Abdelsamie (2016).Effect of ginko biloba extract on cyclophosphamide-induced nephrotoxicity and oxidative stress in albino rats. Canadian J. Pure Appl Sci. 10(2): 3835-3845.
- Turk G., Eribas A., Sakin F., Sonmez M., Ates S., Ahin A.(2010): Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis. Reprod. Fertil. Dev. ;22:587–596
- Naeem M Rabeh, Alaa O Aboraya.(2014): Hepatoprotective effect of Dill (Anethum graveolens L.) and fennel ( Foeniculum vulgare ) oil on hepatotoxic rats. Pak. J. Nut.13(6):303-309.
- Ceribasi AO, Turk G, Sonmez M, Sakin F, Atessahin A.(2010): Toxic effect of cyclophosphamide on sperm morphology, testicular histology and blood oxidant antioxidant balance, and protective roles of lycopene and ellagic acid. Basic and Clinical Pharmacology and Toxicology. 107(3):730-736.
- Hus SM, Raine L, Franger H. (1981): Use of Avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: A comparison of ABC and unlabeled antibody (PAP) procedure. J. Histochem. Cytochem.;29(4):577-580.
- Henry, R.J. (1974): Creatinine Measurements with Colorimetric Method. Clin Chem Principles and Techniques. Harper& Row Publishers.
- Patton, C.J. and Crouch, S. R. (1977): Spectrophotometric and kinetics investigation of the Berthelot reaction for the determination of ammonia. Anal Chem., 49: 464-469.
- Estakhri, R.; Hajipour, B.; Majidi, H. and Soleimani, H. (2013): Vitamin E ameliorates cyclophosphamide induced nephrotoxicity. Life Sci J., 10(6s):308-313.
- Abraham, P. and Rabi, S. (2009): Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide. Clin Exp Nephrol., 13: 281–287.
- -Kelman,Z. (1997). PCNA: structure, functions and interactions. Oncogen, 14: 629–640.
- Romih R, Koprivec D, Štiblar-Martinčič D, Jezernik K.(2001): Restoration of the rat urothelium after cyclophosphamide treatment. Cell Biol Int. 25:531–537
- Elmore S. (2007). Apoptosis: a review of programmed cell death.Toxicol Pathol.;35(4):495-516.
- Porter, A.G. and Janicke, R.U. (1999): Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6: 99–104
- Sultan, A. and Ayman M. Mahmoud. (2016): Gamma-Glutamylcysteine Ethyl Ester protects against cyclophosphamide-induced liver injury and hematologic alterations via upregulation of PPAR and attenuation of oxidative stress, inflammation, and apoptosis. Oxidative Medicine and Cellular Longevity 1-14.
- Groma, V.;Marcussen, N.and Olsen, S. (1997):Aquantitative immunohistochemical study of the expression of mesangial alpha-smooth muscle actin and proliferation marker Ki-67 in glomerulonephritis in man. Virchows Archives, 431: 345- 350.
- Ludeman S M. (1999): The chemistry of the metabolites of cyclophosphamide. Curr Pharm .5:627–43
- -Kern JC, Kehrer JP.(2002). Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact. 139:79–95.
- Arumugam N, Sivakumar V, Thanislass J, Devaraj H.(1997): Effects of acrolein on rat liver antioxidant defense system. Indian J Exp Biol 35:1373–4.
- Bhatia A L, Manda K, Patni S, Sharma A L. (2006): Prophylactic action of linseed (Linum usitatissimum) oil against cyclophosphamide induced oxidative stress on mouse brain. J Med Food. 9:21–264.
- Stankiewicz, A, Skrzydlewska E, Makieła M. (2002). Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats. Drug Metabol Drug Interact. 19(2):67-82
- Al-Masri,S. and Ali, W.(2013).The Ameliorating Effects of Fennel Powder, Extract and Oil on Gentamicin Induced Nephrotoxicity in Rats. J Am Sci 9(10):20- 25
- Al-Amoudi, W.M. (2016): Protective effects of fennel oil extract against sodium valproate-induced hepatorenal damage in albino rats. Saudi Journal of Biological Sciences, 24(4): 915-924
- Ibrahim, A. A. E. (2007): Does fennel oil have the potentials against apoptosis in testes of rats exposed to mainstream tobacco smoke? Egyptian Journal of Medical Science 28(2): 767-783
- Singh, G.; Maurya, S.; de-Lampasona, M.P. and Catalan, C. (2006): Chemical constituents, antifungal and antioxidative potential of Foeniculum vulgare volatile oil and its acetone extract. Food Control, 17(9): 745–752.
- Sheweita SA, El-Hosseiny LS, Nashashibi MA (2016): Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice. PLoS ONE11(11): e0165667. doi:10.1371/journal. pone.0165667
- Sakr A. Saber , Shalaby Y. Somaya and Beder H. Rawan (2017). Ameliorative Effect of Fennel Oil on Cyclophosphamide Induced Hepatotoxicity in Albino Rats : British Journal of Pharmaceutical Research 17(2): 1-12, 2017.
International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.