JRI 

Effects of Vitamin E and Ginseng Extract on Fertility Changes Induced by Cyclophosphamide in Rats

Vol. 11, Issue 4, / December 2010
(pages 227-237)

Akram Hosseini
- Department of Biology, Faculty of Sciences, Urmia University, Urmia, Iran
Samad Zare
- Department of Biology, Faculty of Sciences, Urmia University, Urmia, Iran
Firouz Ghaderi Pakdel Corresponding Author
- Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
Abbas Ahmadi
- Department of Embryology, Faculty of Veterinary, Urmia University, Urmia, Iran

Received: 4/24/2010 Accepted: 6/28/2010 - Publisher : Avicenna Research Institute

Related Articles
in Google Scholar
in PubMed

 

Other Format
pdfFull Text (En)
pdfFull Text (Fa)
pdfAbstract (En)
pdfAbstract (Fa)
pdfePUB (En)
pdfBibTeX
pdfRefMan
pdfEndNote
xmlPMC XML
online readerPMC Reader
online readerHBIs XML

 


Abstract

Background: Cyclophosphamide (CP) is a mustard alkylating agent used in the treatment of some neoplastic diseases such as leukemia, breast and pulmonary cancers. CP administration induces oxidative stress and has cytotoxic effects on normal cells, especially in the reproductive organs. A major side-effect of CP is the alteration of male reproductive function which may result in oligospermia or azoospermia. The aim of the present study was to evaluate the protective effects of vitamin E and ginseng extract on the reproductive system of male rats during cyclophosphamide administration. Methods: Fifty-six adult male Wistar rats (220±30 g) were randomly divided into seven groups of eight. To eliminate the stress induced by gavage, the animals in the first group were considered as the control group and only received water and food. The second group received the placebo for CP via gavage. The third group received CP, 6.1 mg/kg/day, through intraperitoneal administration. The fourth and fifth groups, respectively, received Ginseng, 500 mg/kg/day, and vitamin E 100 mg/kg/day via gavage. The eighth group received both antioxidants by intubation 1 h prior to CP administration for 50 days. The animals were sacrificed one day after the last injection. The testes, body weight, sperm parameters and fertility status of animals were evaluated at the end of the experiments. For the evaluation of fertility index, the male rats were mated with untreated female rats on the 40th day of the treatment period. Results: Cyclophosphamide decreased sperm count, lowered fertility rate and decreased testis weight while it increased the number of dead and abnormal sperms (p < 0.01). In addition, the number of pregnant animals and viable offspring were reduced too; while antioxidant use diminished the adverse effects of CP. Conclusion: The results of the study showed that antioxidative agents vitamin E and Ginseng could diminish the adverse effects of cyclophosphamide in the reproductive system of male rats during cyclophosphamide administration.


Keywords: Chemotherapy, Cyclophosphamide, Ginseng, Male infertility, Rat, Reproductive health, Sperm, Vitamin E


To cite this article:



Figures, Charts, Tables





References

  1. Dollery CT. Cyclophosphamide. In: Dollery CT, editors. Therapeutic drugs. Edinburgh: Churchill Livingstone; 1999. p. 349-53.
  2. 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.   [PubMed]
  3. Haque R, Bin-Hafeez B, Ahmad I, Parvez S, Pandey S, Raisuddin S. Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice. Hum Exp Toxicol. 2001;20(12):643-50.   [PubMed]
  4. 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.   [PubMed]
  5. 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.   [PubMed]
  6. Hemminki K, Kallama S. Reactions of nitrogen mustards with DNA. IARC Sci Publ. 1986;(78):55-70.   [PubMed]
  7. Hengstler JG, Fuchs J, Tanner B, Oesch Bartlomowicz B, Hölz C, Oesch F. Analysis of DNA single-strand breaks in human venous blood: a technique which does not require isolation of white blood cells. Environ Mol Mutagen. 1997;29(1):58-62.   [PubMed]
  8. Qiu J, Hales BF, Robaire B. Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure. Biol Reprod. 1995;53(6):1465-73.   [PubMed]
  9. 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.   [PubMed]
  10. Mythili Y, Sudharsan PT, Selvakumar E, Varalakshmi P. Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chem Biol Interact. 2004;151(1):13-9.   [PubMed]
  11. 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.   [PubMed]
  12. 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.   [PubMed]
  13. Ghosh D, Das UB, Misro M. Protective role of alpha-tocopherol-succinate (provitamin-E) in cyclo phosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic Res. 2002;36(11): 1209-18.   [PubMed]
  14. Ocollura J. Ginseng tonic of life. Vegetarian Times. 1997;235:94.
  15. Hu SY. A contribution to our knowledge of ginseng. Am J Chin Med (Gard City N Y). 1977;5(1): 1-23.   [PubMed]
  16. Kumar A. Chemopreventive action of ginseng on DMBA induced skin papillomagenesis in the skin of Swiss albino mice. Proceedings of the 6th International Ginseng Symposium; 1993 Sept 6-9; Seoul Olympic Parktel. Seoul, Korea: Korea Ginseng & Tobacco Research Institute; 1993. P. 66-8.
  17. Cheng LQ, Kim MK, Lee JW, Lee YJ, Yang DC. Conversion of major ginsenoside Rb1 to ginsenoside F2 by Caulobacter leidyia. Biotechnol Lett. 2006;28:1121-27.
  18. Helms S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev. 2004;9(3):259-74.   [PubMed]
  19. Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutr. 2000;3(4A):473-85.   [PubMed]
  20. Chang YS, Seo EK, Gyllenhaal C, Block KI. Panax ginseng: a role in cancer therapy? Integr Cancer Ther. 2003;2(1):13-33.   [PubMed]
  21. Benishin CG, Lee R, Wang LC, Liu HJ. Effects of ginsenoside Rb1 on central cholinergic metabolism. Pharmacology. 1991;42(4):223-9.   [PubMed]
  22. Saito H, Tsuchiya M, Naka S, Takagi K. Effects of Panax Ginseng root on conditioned avoidance response in rats. Jpn J Pharmacol. 1977;27(4):509-16.   [PubMed]
  23. Scott GI, Colligan PB, Ren BH, Ren J. Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide. Br J Pharmacol. 2001;134(6):1159-65.   [PubMed]
  24. Mahady GB, Gyllenhaal C, Fong HHS, Farnsworth NR. Ginsengs: A review of safety and efficacy. Nutr Clin Care. 2000;3(2):90-101.   [Abstract]
  25. Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. Eur J Clin Pharmacol. 1999;55(8):567-75.   [PubMed]
  26. Bastianetto S, Zheng WH, Quirion R. The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C. J Neurochem. 2000;74(6):2268-77.   [PubMed]
  27. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control. 2000;11(6):565-76.   [PubMed]
  28. Gurel A, Coskun O, Armutcu F, Kanter M, Ozen OA. Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: biochemical and histological studies. J Chem Neuroanat. 2005;29(3):173-8.   [PubMed]
  29. Nouri M, Ghasemzadeh A, Farzadi L, Shahnazi V, Ghaffari Novin M. Vitamins C, E and lipid peroxidation levels in sperm and seminal plasma of asthenoteratozoospermic and normozoospermic men. Iran J Reprod Med. 2008;6(1):1-5.
  30. Yoganathan T, Eskild W, Hansson V. Investigation of detoxification capacity of rat testicular germ cells and Sertoli cells. Free Radic Biol Med. 1989; 7(4):355-9.   [PubMed]
  31. Ricciarelli R, Zingg JM, Azzi A. Vitamin E: protective role of a Janus molecule. FASEB J. 2001;15 (13):2314-25.   [PubMed]
  32. Sabik LME, Abd El-Rahman SS. Alpha-tocopherol and ginger are protective on Cyclophosphamide-induced gonadal toxicity in adult male albino rats. Basic Appl Pathol. 2009;2(1):21-9.   [Abstract]
  33. Codrington AM, Hales BF, Robaire B. Spermiogenic germ cell phase–specific DNA damage following cyclophosphamide exposure. J Androl. 2004;25(3):354-62.   [Abstract]
  34. Codrington AM, Hales BF, Robaire B. Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa. Hum Reprod. 2007;22(5):1431-42.   [PubMed]
  35. Rezvanfar M, Sadrkhanlou R, Ahmadi A, Shojaei-Sadee H, Rezvanfar M, Mohammadirad A, et al. Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics, and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum Exp Toxicol. 2008;27(12):901-10.
  36. Lear L, Nation RL, Stupans I. Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem Pharmacol. 1992;44(4):747-53.   [PubMed]
  37. Das UB, Mallick M, Debnath JM, Ghosh D. Protective effect of ascorbic acid on cyclophospha-mide induced testicular gametogenic and androgenic disorders in male rats. Asian J Androl. 2002; 4(3):201-7.   [PubMed]
  38. Higuchi H, Nakaoka M, Katsuda Y, Kawamura S, Kato T, Matsuo M. Collaborative assessment of optimal administration period and parameters to detect effects on male fertility in the rat: effects of cyclophosphamide on the male reproductive system. J Toxicol Sci. 1995;20(3):239-49.   [PubMed]
  39. Robaire B, Hales BF. Mechanisms of action of cyclophosphamide as a male-mediated developmental toxicant. Adv Exp Med Biol. 2003;518: 169-80.   [PubMed]
  40. Moore HD, Akhondi MA. In vitro maturation of mammalian spermatozoa. Rev Reprod. 1996;1(1): 54-60.   [PubMed]
  41. 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.   [PubMed]
  42. Robaire B, Hermo L. Efferent ducts, epididymis, and vas deferens: structure, functions, and their regulation. In: Knobil E, Neill JD, editors. The physiology of reproduction. New York: Raven Press; 1988. p. 999-1080.
  43. de Jager C, Bornman MS, van der Horst G. The effect of p-nonylphenol, an environmental toxicant with oestrogenic properties, on fertility potential in adult male rats. Andrologia. 1999;31(2):99-106.   [PubMed]
  44. Agarwal A, Saleh RA. Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am. 2002;29(4):817-27.   [PubMed]
  45. Agarwal A, Allamaneni SS. Role of free radicals in female reproductive diseases and assisted reproduction. Reprod Biomed Online. 2004;9(3):338-47.   [PubMed]
  46. Sies H. Strategies of antioxidant defense. Eur J Biochem. 1993;215(2):213-9.   [PubMed]
  47. Lewis SE, Boyle PM, McKinney KA, Young IS, Thompson W. Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril. 1995;64(4):868-70.   [PubMed]
  48. Huszar G, Sbracia M, Vigue L, Miller DJ, Shur BD. Sperm plasma membrane remodeling during spermiogenetic maturation in men: relationship among plasma membrane beta 1,4-galactosyl-transferase, cytoplasmic creatine phosphokinase, and creatine phosphokinase isoform ratios. Biol Reprod. 1997;56(4):1020-4.   [PubMed]
  49. Gomez E, Buckingham DW, Brindle J, Lanzafame F, Irvine DS, Aitken RJ. Development of an image analysis system to monitor the retention of residual cytoplasm by human spermatozoa: correlation with biochemical markers of the cytoplasmic space, oxidative stress, and sperm function. J Androl. 1996;17(3):276-87.   [PubMed]
  50. Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992;57(2):409-16.   [PubMed]
  51. Cao L, Leers-Sucheta S, Azhar S. Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells. J Steroid Biochem Mol Biol. 2004;88(1):61-7.   [PubMed]
  52. Aziz N, Saleh RA, Sharma RK, Lewis-Jones I, Esfandiari N, Thomas AJ Jr, et al. Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril. 2004;81(2): 349-54.   [PubMed]
  53. Johnson FC. The antioxidant vitamins. CRC Crit Rev Food Sci Nutr. 1979;11(3):217-309.   [PubMed]
  54. Verma A, Kanwar KC. Effect of vitamin E on human sperm motility and lipid peroxidation in vitro. Asian J Androl. 1999;1(3):151-4.   [PubMed]
  55. Aitken RJ, Clarkson JS. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil. 1987;81(2):459-69.   [PubMed]
  56. Lucesoli F, Fraga CG. Oxidative stress in testes of rats subjected to chronic iron intoxication and alpha-tocopherol supplementation. Toxicology. 1999;132(2-3):179-86.   [PubMed]
  57. Gavazza MB, Catalá A. The effect of alpha-tocopherol on lipid peroxidation of microsomes and mitochondria from rat testis. Prostaglandins Leukot Essent Fatty Acids. 2006;74(4):247-54.   [PubMed]
  58. Senthil kumar J, Banudevi S, Sharmila M, Murugesan P, Srinivasan N, Balasubramanian K, et al. Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells. Reprod Toxicol. 2004;19(2):201-8.   [PubMed]
  59. Sen Gupta R, Sen Gupta E, Dhakal BK, Thakur AR, Ahnn J. Vitamin C and vitamin E protect the rat testes from cadmium-induced reactive oxygen species. Mol Cells. 2004;17(1):132-9.   [PubMed]
  60. Verma RJ, Nair A. Ameliorative effect of vitamin E on aflatoxin-induced lipid peroxidation in the testis of mice. Asian J Androl. 2001;3(3):217-21.   [PubMed]
  61. Latchoumycandane C, Mathur PP. Effects of vitamin E on reactive oxygen species-mediated 2,3, 7,8-tetrachlorodi-benzo-p-dioxin toxicity in rat testis. J Appl Toxicol. 2002;22(5):345-51.   [PubMed]
  62. Manna I, Jana K, Samanta PK. Intensive swimming exercise-induced oxidative stress and reproductive dysfunction in male wistar rats: protective role of alpha-tocopherol succinate. Can J Appl Physiol. 2004;29(2):172-85.   [PubMed]
  63. Jedlinska-Krakowska M, Bomba G, Jakubowski K, Rotkiewicz T, Jana B, Penkowski A. Impact of oxidative stress and supplementation with vitamins E and C on testes morphology in rats. J Reprod Dev. 2006;52(2):203-9.   [PubMed]
  64. Zhou DX, Qiu SD, Zhang J, Tian H, Wang HX. The protective effect of vitamin E against oxidative damage caused by formaldehyde in the testes of adult rats. Asian J Androl. 2006;8(5):584-8.   [PubMed]
  65. Kim YS, Kang KS, Kim SI. Effects of ginseng components on immunotoxicity of cyclophosphamide. Kor J Ginseng Sci1991;15:13-20.
  66. Kang J, Lee Y, No K, Jung E, Sung J, Kim Y, et al. Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis. Reprod Toxicol. 2002;16(3):291-8.   [PubMed]
  67. Kang KS, Kim HY, Pyo JS, Yokozawa T. Increase in the free radical scavenging activity of ginseng by heat-processing. Biol Pharm Bull. 2006;29(4): 750-4.   [PubMed]
  68. Liu ZQ, Luo XY, Liu GZ, Chen YP, Wang ZC, Sun YX. In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J Agric Food Chem. 2003;51(9):2555-8.   [PubMed]
  69. Naval MV, Gómez-Serranillos MP, Carretero ME, Villar AM. Neuroprotective effect of a ginseng (Panax ginseng) root extract on astrocytes primary culture. J Ethnopharmacol. 2007;112(2):262-70.   [PubMed]
  70. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999;58(11):1685-93.   [PubMed]

COPE
SID
NLM
AJMB
IJBMLE
IJBMLE

Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and managed by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution –NonCommercial 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2024 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.