Crataegus monogyna Aqueous Extract Ameliorates Cyclophosphamide-Induced Toxicity in Rat Testis: Stereological Evidences
,
Abstract
Cyclophosphamide (CP) is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices) were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.
Dollery C, editor. Therapeutic Drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. 349-54.
Ludeman SM. The chemistry of the metabolites of cyclophosphamide. Curr Pharm Des 1999;5(8):627-43.
Kern JC, Kehrer JP. Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact 2002;139(1):79-95.
Anderson D, Bishop JB, Garner RC, Ostrosky-Wegman P, Selby PB. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res 1995;330(1-2):115-81.
Howell S, Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 1998;27(4):927-43.
Meistrich ML, Parchuri N, Wilson G, Kurdoglu B, Kangasniemi M. Hormonal protection from cyclophosphamide-induced inactivation of rat stem spermatogonia. J Androl 1995;16(4):334-41.
Kaur F, Sangha GK, Bilaspuri GS. Cyclophosphamideinduced structural and biochemical changes in testis and epididymidis of rats. Indian J Exp Biol 1997;35(7):771-5.
Trasler JM, Hales BF, Robaire B. Chronic low dose cyclophosphamide treatment of adult male rats: effect on fertility, pregnancy outcome and progeny. Biol Reprod 1986;34(2):275-83.
Das UB, Mallick M, Debnath JM, Ghosh D. Protective effect of ascorbic acid on cyclophosphamide- induced testicular gametogenic and androgenic disorders in male rats. Asian J Androl 2002;4(3):201-7.
Ghosh D, Das UB, Ghosh S, Mallick M, Debnath J. Testicular gametogenic and steroidogenic activities in cyclophosphamide treated rat: a correlative study with testicular oxidative stress. Drug Chem Toxicol 2002;25(3):281-92.
Manda K, Bhatia AL. Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice. Cell Biol Toxicol 2003;19(6):367-72.
Murata M, Suzuki T, Midorikawa K, Oikawa S, Kawanishi S. Oxidative DNA damage induced by a hydroperoxide derivative of cyclophosphamide. Free Radic Biol Med 2004;37(6):793-802.
Arumugam N, Sivakumar V, Thanislass J, Devaraj H. Effects of acrolein on rat liver antioxidant defense system. Indian J Exp Biol 1997;35(12):1373-4.
Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of hawthorn. J Ethnopharmacol 2008;118(1):127-32.
Bahorun T, Gressier B, Trotin F, Brunet C, Dine T, Luyckx M, Vasseur J, Cazin M, Cazin JC, Pinkas M. Oxygen species scavenging activity of phenolic extractsfrom hawthorn fresh plant organs and pharmaceutical preparations. Arzneimittelforschung 1996;46(11):1086-9.
Ljubuncic P, Azaizeh H, Portnaya I, Cogan U, Said O,Saleh KA, Bomzon A. Antioxidant activity and cytotoxicity of eight plants used in traditional Arab medicine in Israel. J Ethnopharmacol 2005;99(1):43-7.
Bahorun T, Trotin F, Pommery J, Vasseur J, Pinkas M. Antioxidant activities of Crataegus monogyna extracts. Planta Med 1994;60(4):323-8.
Zhang Z, Chang Q, Zhu M, Huang Y, Ho WK, Chen Z. Characterization of antioxidants present in hawthorn fruits. J Nutr Biochem 2001;12(3):144-152.
Rice-Evans C. Flavonoids and isoflavones: absorption, metabolism, and bioactivity. Free Radic Biol Med2004;36(7):827-8.
Khalil R, Abuharfeil N, Shabsoug B. The effect ofCrataegus aronica aqueous extract in rabbits fed with high cholesterol diet. European J Sci Res 2008;22(3):352-60.
Qin DN, Lung MA. Morphometric study on leydig cells in capsulotomized testis of rats. Asian J Androl 2002;4(1):49-53.
Vendramini V, Sasso-Cerri E, Miraglia SM. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status. Reprod Biol Endocrinol 2010;8:3.
Gundersen HJ, Jensen EB. The efficiency of systematic sampling in stereology and its prediction. J Microsc 1987;147(Pt 3):229-63.
Gundersen HJG. Notes on the estimation of the numerical density of arbitrary profiles: the edge effect. J Microsc1977;111:219-23.
Gilliland KO, Freel CD, Lane CW, Fowler WC, Costello MJ. Multilamellar bodies as potential scattering particles in human age-related nuclear cataracts. Mol Vis 2001;7:120-30.
Russell LD, Ettlin R, Sinha Hikim AP, Clegg ED, editors. Histological and Histopathological Evaluation of theTestis. Clearwater, FL: Cache River Press; 1990.
Meistrich ML, van Beek MEAB. Spermatogonial stem cells: assessing their survival and ability to produce differentiated cells. Methods Toxicol 1993;3A:106-23.
Kheradmand A, Dezfoulian O, Tarrahi MJ. Ghrelin attenuates heat-induced degenerative effects in the rat testis. Regul Pept 2011;167(1):97-104
Elias H, Hyde DM. An elementary introduction to stereology (quantitative microscopy). Am J Anat1980;159(4):412-46.
Sawada T, Tamada H, Mori J. Secretion of testosterone and epidermal growth factor in mice with oligozoospermia caused by doxorubicin hydrochloride. Andrologia1994;26(3):151-3.
Lear L, Nation RL, Stupans I. Effects ofcyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem Pharmacol 1992;44(4):747-53.
Katoh C, Kitajima S, Saga Y, Kanno J, Horii I, Inoue T. Assessment of quantitative dual-parameter flow cytometricanalysis for the evaluation of testicular toxicity using cyclophosphamide- and ethinylestradiol-treated rats. J Toxicol Sci 2002;27(2):87-96.
Meistrich ML. Relationship between spermatogonial stem cell survival and testis function after cytotoxic therapy. Br J Cancer Suppl 1986;7:89-101.
Franca LR, Russell LD. The testis of domestic animals. In: Regadera J, Martinez-Garcia F, editors. Male Reproduction: A Multidisciplinary Overview. Madrid,Spain: Churchill Livingstone; 1998. p. 198-219.
Debnath D, Mandal TK. Study of quinalphos (an environmental oestrogenic insecticide) formulation (Ekalux 25 E.C.)-induced damage of the testicular tissues and antioxidant defence systems in Sprague-Dawley albino rats. J Appl Toxicol 2000;20(3):197-204.
Mruk DD, Cheng CY. Sertoli-Sertoli and Sertoligerm cell interactions and their significance in germ cell movement in the seminiferous epitheliumduring spermatogenesis. Endocr Rev 2004;25(5):747-806.
Ghosh D, Das UB, Misro M. Protective role of alphatocopherol- succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic Res 2002;36(11):1209-18.
Oh MS, Chang MS, Park W, Kim do R, Bae H, Huh Y, Park SK. Yukmijihwang-tang protects against cyclophosphamide-induced reproductive toxicity. Reprod Toxicol 2007;24(3-4):365-70.
Selvakumar E, Prahalathan C, Sudharsan PT, VaralakshmiP. Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm. Toxicology 2006;217(1):71-8.
Selvakumar E, Prahalathan C, Sudharsan PT, Varalakshmi P. Protective effect of lipoic acid on cyclophosphamideinduced testicular toxicity. Clin Chim Acta 2006;367(1-2):114-9.
Hosseinimehr SJ, Azadbakht M, Abadi AJ. Protective effect of hawthorn extract against genotoxicity induced by cyclophosphamide in mouse bone marrow cells. Environ Toxicol Pharmacol 2008;25(1):51-6.
Elango C, Jayachandaran KS, Niranjali Devaraj S. Hawthorn extract reduces infarct volume and improvesneurological score by reducing oxidative stress in rat brain following middle cerebral artery occlusion. Int J Dev Neurosci 2009;27(8):799-803.
| Files | ||
| Issue | Vol 50, No 1 (2012) | |
| Section | Original Article(s) | |
| Keywords | ||
| Crataegus monogyna Cyclophosphamide Toxicity Testis | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
