Volume 13, Issue 5 (7-2015)                   IJRM 2015, 13(5): 291-296 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Bakhtiary Z, Shahrooz R, Ahmadi A, Zarei L. Protective effects of ethyl pyruvate on sperm quality in cyclophosphamide treated mice. IJRM. 2015; 13 (5) :291-296
URL: http://ijrm.ssu.ac.ir/article-1-648-en.html
1- Department of Comparative Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran , sara_bakhtiari1@yahoo.com
2- Department of Comparative Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
3- Solid Tumor Research Center, Urmia University of Medical Science, Urmia, Iran
Abstract:   (1692 Views)
Background: One of the affecting factors in disturbance process of spermatogenesis is chemotherapeutic-induced oxidative stress resulted from cyclophosphamide (CP) treatment which leads to diminished sperm quality via interference in spermatogenesis process.
Objective: This study was conducted to investigate the effects of ethyl pyruvate (EP) in reducing the CP-induced side effects on reproductive system.
Materials and Methods: 24 mature male mice were randomly divided into 3 equal groups and were undergone therapy for 35 days. Control group received normal saline (0.1 ml/day, IP). CP group were injected CP (15 mg/kg/week, IP) and CP+EP group received EP (40 mg/kg/day, IP) as well as CP. In the end of the treatment period, the mice were euthanized by cervical dislocation. Then, the epididymis was incubated with CO2 in a human tubal fluid medium (1 ml) for half an hour in order to float sperm. Then, the number, motility, viability (eosin-nigrosin staining), DNA breakage (acridine orange staining), nucleus maturity, and sperm morphology (aniline blue staining) were analyzed.
Results: The average (15.87±1.28), motility (35.77±2.75), viability (40±3.03), nucleus maturity (36±2.79) and sperm morphology (61.75±0.85) were decreased significantly in CP group in comparison with control and EP groups, whereas EP caused significant increase of these parameters. Also, the percentage of DNA damage was increased significantly in CP group (41.75±3.75) in comparison with control (2±0.71) and EP groups (22.5±4.13).
Conclusion: The results of this study revealed ameliorating effects of EP on sperm quality of CP treated animals.
Full-Text [PDF 132 kb]   (386 Downloads) |   |   Full-Text (HTML)  (212 Views)  
Type of Study: Original Article |

1. El-Sayyad HI, Ismail MF, Shalaby FM, Abou-El-Magd RF, Gaur RL, Fernando A, et al. Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. Int J Biol Sci 2009; 5: 466-473. [DOI:10.7150/ijbs.5.466]
2. Weigl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev 1997; 23: 209-240. [DOI:10.1016/S0305-7372(97)90012-8]
3. Robair B, Hales BF. Mechanisms of action of cyclophosphamide as a male-mediated developmental toxicant. Adv Exp Med Biol 2003; 518: 169-180. [DOI:10.1007/978-1-4419-9190-4_14]
4. Brock N. Oxazaphosphorinecytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res 1989; 49: 1-7.
5. Howell S, Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 1998; 27: 927-943. [DOI:10.1016/S0889-8529(05)70048-7]
6. Ludeman SM, The chemistry of the metabolites of cyclophosphamide. Curr Pharm Des 1999; 5: 627-643.
7. Arumugam N, Silvakumar V, Thanislass J, Devaraj H. Effects of acrolein on rat liver antioxidant defense system. Indian J Exp Biol 1997; 35: 1373-1374.
8. Mythili Y, Sudharsan PT, Sulvakumar E, Varalakshmi P. Protective effect of DL-α-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chem Biol Interact 2004; 151: 13-19. [DOI:10.1016/j.cbi.2004.10.004]
9. Gonzalez-Flecha B, Reides C, Cutrin JC, Liesuy SF, Boveris A. Oxidative stress produced by suprahepatic occlusion and reperfusion. Hepatology 1993; 18: 881-889. [DOI:10.1002/hep.1840180421]
10. Sikka SC. Relative impact of oxidative stress on male reproductive function. Curr Med Chem 2001; 8: 851-862. [DOI:10.2174/0929867013373039]
11. Qureshi MS, Pennington JH, Goldsmith HJ, Cox PE. Cyclophosphamide therapy and sterility. Lancet 1972; 2: 1290-1291. [DOI:10.1016/S0140-6736(72)92657-8]
12. Chapman RM. Gonadal injury resulting from chemotherapy. Am J Ind Med 1983; 4: 149-161. [DOI:10.1002/ajim.1983.4.1-2.149]
13. Vernet P, Aitken RJ, Drevet JR. Antioxidant strategies in the epididymis. Mol Cell Endocrinol 2004; 216: 31-39. [DOI:10.1016/j.mce.2003.10.069]
14. 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: 793-802. [DOI:10.1016/j.freeradbiomed.2004.05.009]
15. Greco E, Romano S, Iacobelli M, Ferrero S, Baroni E, Minasi MG. ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment. Hum Reprod 2005; 20: 2590-2594. [DOI:10.1093/humrep/dei091]
16. Hughes CM, Lewis SE, McKelvey-Martin VJ, Thompson W. The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity. Hum Reprod 1998; 13: 1240-1247. [DOI:10.1093/humrep/13.5.1240]
17. Rezvanfar MA, Sadrkhanlou RA, Ahmadi A, Shojaei-Sadee H, A Mohammadirad, Salehnia 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: 901. [DOI:10.1177/0960327108102046]
18. ShalizarJalali A, Hasanzadeh SH, Malekinejad H. Achillea millefolium inflorescence aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis: stereological evidences. Chinese J Natural Med 2012; 10: 247-254. [DOI:10.3724/SP.J.1009.2012.00247]
19. Wang X, Perez E, Liu R, Yan LJ, Mallet RT, Yang SH. Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells. Brain Res 2007; 1132: 1-9. [DOI:10.1016/j.brainres.2006.11.032]
20. Jagtap JC, Chandele A, Chopde BA, Shastry P. Sodium pyruvate protects against H(2)O(2) mediated apoptosis in human neuroblastoma cell line-SK-NMC. J Chem Neuroanat 2003; 26: 109-118. [DOI:10.1016/S0891-0618(03)00037-1]
21. Hinoi E, Takarada T, Tsuchihashi Y, Fujimori S, Moriguchi N, Wang L, et al. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol 2006; 70: 925-935. [DOI:10.1124/mol.106.024398]
22. Suffoletto BP, Salcido DD, Logue ES, Caprio TW, Menegazzi JJ. Ethyl pyruvate enhances intra-resuscitation hemodynamics in prolonged ventricular fibrillation arrest. Resuscitation 2009; 80: 1411-1416. [DOI:10.1016/j.resuscitation.2009.08.014]
23. Johansson AS, Palmblad J. Ethyl pyruvate modulates adhesive and secretory reactions in human lung epithelial cells. Life Sci 2009; 84: 805-809. [DOI:10.1016/j.lfs.2009.03.012]
24. Cai B, Brunner M, Wang H, Wang P, Deitch EA, Ulloa L. Ethyl pyruvate improves survival in awake hemorrhage. J Mol Med 2009; 87: 423-433. [DOI:10.1007/s00109-009-0441-8]
25. Atashfaraz E, Farokhi F, Najafi GH. Protective Effect of Ethyl Pyruvate on Epididymal Sperm Characteristics, Oxidative Stress and Testosterone Level in Methotrexate Treated Mice. J Reprod Infertil 2013; 14: 190-196.
26. Selvakumar E, Prahalathan C, Sudharsan PT, and Varalakshmi P. Protective effect of lipoic acid on cyclophosphamide-induced testicular toxicity. Clinia Chimica Acta 2006; 367: 114-119. [DOI:10.1016/j.cca.2005.11.034]
27. Yang R, Shaufl AL, Killeen ME, Fink MP. Ethyl pyruvate ameliorates liver injury secondary to severe acute pancreatitis. J Surg Res 2009; 153: 302-309. [DOI:10.1016/j.jss.2008.04.004]
28. Hedrich H. The Laboratory mouse: Handbook of experimental animals. 2nd Ed. New York, USA: Academic press 2006; 439-446.
29. Zobeiri F, Sadrkhanlou RA, Salami S, Mardani K, Ahmadi A. The effect of ciprofloxacin on sperm DNA damage, fertility potential and early embryonic development in NMRI mice. Veterinary Research Forum 2012; 3: 131-135.
30. Mehraban F, Jafari M, Akbartabar Toori M, Sadeghi H, Joodi B, Mostafazade M, et al. Effects of date palm pollen (Phoenix dactylifera L.) and Astragalus ovinus on sperm parameters and sex hormones in adult male rats. Iran J Reprod Med 2014; 12: 705-712.
31. Erenpreiss J, Bars J, Lipatnikova V, Erenpreisa J, Zalkalns J. Comprative study of cytochemical tests for sperm chromatin integrity. J Androl 2001; 22: 45-53.
32. Bakhtiary Z, Shahrooz R, Ahmadi A, Zarei L. Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice. Veterinary Research Forum 2014; 5: 213-218.
33. Meistrich ML. Relationship between spermatogonial stem cell survival and testis function after cytotoxic therapy. Brit J Cancer 1986; 53: 89-101.
34. Kumar TR, Doreswamy K, Shrilatha B, Muralidhara. Oxidative stress associated DNA damage in testis of mice: induction of abnormal sperms and effects on fertility. Mutat Res 2002; 513: 103-111. [DOI:10.1016/S1383-5718(01)00300-X]
35. Koppers AJ, De luliis GN, Finnie JM, McLaughlin EA, Aiyken RJ. Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa. J Clin Endocrinol Metab 2008; 93: 3199-3207. [DOI:10.1210/jc.2007-2616]
36. 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: 201-207.
37. Ghosh D, Das UB, Misro M. Protective role of alpha-tocopherol- succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic Res 2002; 36: 1209-1218. [DOI:10.1080/1071576021000016472]
38. Manda K, Bhatia AL. Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice. Cell Biol Toxicol 2003; 19: 367-372. [DOI:10.1023/B:CBTO.0000013342.17370.16]
39. Iwasaki A, Gagnon C. Formation of oxygen reactive species in spermatozoa of infertile patients. Fertil Steril 1992; 57: 409-416. [DOI:10.1016/S0015-0282(16)54855-9]
40. Twigg J, Irvine DS, Aitken RJ. Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intra cytoplasmic sperm injection. Hum Reprod 1998; 13: 1864-1871. [DOI:10.1093/humrep/13.7.1864]
41. Duru NK, Moshedi M, Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril 2000; 74: 1200-1207. [DOI:10.1016/S0015-0282(00)01591-0]
42. Lee J, Kwon W, Jo Y,Suh G, Youn Y. Protective effects of ethyl pyruvate treatment on paraquat-intoxicated rats. Hum Exp Toxicol 2008; 27: 49-54. [DOI:10.1177/0960327108088976]
43. Wang Q, Ding Q, Zhou Y, Gou X, Hou L, Chen S, et al. Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits. Anesthesiology 2009; 110: 1279-1286. [DOI:10.1097/ALN.0b013e3181a160d6]

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb