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Volume 11, Issue 5 (7-2013)
IJRM 2013, 11(5): 355-0 |
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Badkoobeh P, Parivar K, Kalantar S M, Hosseini S D, Salabat A. Effect of nano-zinc oxide on doxorubicin- induced oxidative stress and sperm disorders in adult male Wistar rats. IJRM 2013; 11 (5) :355-0
URL: http://ijrm.ir/article-1-424-en.html
URL: http://ijrm.ir/article-1-424-en.html
Puran Badkoobeh1 
, Kazem Parivar * 2, Seyed Mehdi Kalantar3 , Seyed Davood Hosseini4 , Alireza Salabat5
, Kazem Parivar * 2, Seyed Mehdi Kalantar3 , Seyed Davood Hosseini4 , Alireza Salabat5
1- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran ,k_parivar@yahoo.com
3- Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4- Razi Vaccine and Serum Research Institute, Central Area Branch, Arak, Iran
5- Department of Chemistry, Arak University, Arak, Iran
2- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran ,
3- Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4- Razi Vaccine and Serum Research Institute, Central Area Branch, Arak, Iran
5- Department of Chemistry, Arak University, Arak, Iran
Abstract: (3585 Views)
Background: Doxorubicin (DOX), an anthracycline antibiotic, is a widely used anticancer agent. In spite of its high antitumor efficacy, the use of DOX in clinical chemotherapy is limited due to diverse toxicities, including gonadotoxicity.
Objective: We investigated the protective effect of nano-zinc oxide (nZnO) as an established antioxidant on DOX-induced testicular disorders.
Materials and Methods: In this experimental study 24 adult male Wistar rats were divided into four groups including one control and three experimentals (6 rats per group). They received saline (as control), DOX alone (6 mg/kg body weight, i.p.), nZnO alone (5 mg/kg body weight, i.p.), and nZnO followed by DOX. Animals were sacrificed 28 days after treatment and evaluations were made by sperm count and measuring sex hormone levels in plasma. Also total antioxidant power (TAP) and lipid peroxidation (LPO) in plasma were tested. Data was analyzed with SPSS-14 and one way ANOVA test. P<0.05 were considered to be statistically significant.
Results: In the DOX-exposed rats significant differences were found compared with the control group (p=0.001) in plasma total antioxidant power (TAP) (425.50±32.33 vs. 493.33±18.54 mmol/mL), Lipid peroxidation (LPO) (3.70±0.44 vs. 2.78±0.68 μmol/mL), plasma testosterone (3.38±0.69 vs. 5.40±0.89 ng/dl), LH (0.26±0.05 vs. 0.49±0.18 mlU/mL), sperm count (157.98±6.29 vs. 171.71±4.42×106/mL) and DNA damage (11.51±3.45 vs. 6.04±2.83%). Co-administration of nZnO significantly improved DOX-induced changes (p=0.013) in plasma TAP (471.83±14.51 mmol/mL), LPO (2.83±0.75 μmol/mL), plasma testosterone (5.00±1.07 ng/dl), LH (0.52±0.08 mlU/mL), sperm count (169.13±5.01×106/mL) and DNA damage (7.00±1.67%).
Conclusion: At the dose designed in the present investigation cytoprotective role of nano-zinc oxide through its antioxidant potential is illuminated in DOX-induced male gonadotoxicity.
Objective: We investigated the protective effect of nano-zinc oxide (nZnO) as an established antioxidant on DOX-induced testicular disorders.
Materials and Methods: In this experimental study 24 adult male Wistar rats were divided into four groups including one control and three experimentals (6 rats per group). They received saline (as control), DOX alone (6 mg/kg body weight, i.p.), nZnO alone (5 mg/kg body weight, i.p.), and nZnO followed by DOX. Animals were sacrificed 28 days after treatment and evaluations were made by sperm count and measuring sex hormone levels in plasma. Also total antioxidant power (TAP) and lipid peroxidation (LPO) in plasma were tested. Data was analyzed with SPSS-14 and one way ANOVA test. P<0.05 were considered to be statistically significant.
Results: In the DOX-exposed rats significant differences were found compared with the control group (p=0.001) in plasma total antioxidant power (TAP) (425.50±32.33 vs. 493.33±18.54 mmol/mL), Lipid peroxidation (LPO) (3.70±0.44 vs. 2.78±0.68 μmol/mL), plasma testosterone (3.38±0.69 vs. 5.40±0.89 ng/dl), LH (0.26±0.05 vs. 0.49±0.18 mlU/mL), sperm count (157.98±6.29 vs. 171.71±4.42×106/mL) and DNA damage (11.51±3.45 vs. 6.04±2.83%). Co-administration of nZnO significantly improved DOX-induced changes (p=0.013) in plasma TAP (471.83±14.51 mmol/mL), LPO (2.83±0.75 μmol/mL), plasma testosterone (5.00±1.07 ng/dl), LH (0.52±0.08 mlU/mL), sperm count (169.13±5.01×106/mL) and DNA damage (7.00±1.67%).
Conclusion: At the dose designed in the present investigation cytoprotective role of nano-zinc oxide through its antioxidant potential is illuminated in DOX-induced male gonadotoxicity.
Type of Study: Original Article |
References
1. Zanetti SR, Maldonado EN, Avelda-o MI. Doxorubicin Affects Testicular Lipids with Long-Chain (C18-C22) and Very Long-Chain (C24-C32) Polyunsaturated Fatty Acids. Cancer Res 2007; 67: 6973-6980. [DOI:10.1158/0008-5472.CAN-07-0376]
2. Sridevi T. Effect of doxorubicin on the biochemical activities of the male reproductive system of white mice, Mus musculus. Indian J Sci Technol 2011; 4: 1715-1720.
3. Sridevi T, Nisha PV, Appavu Arulnathan G. Effect of Doxorubicin on the morphology, histology and karyology of male reproductive system of white mice, Mus musculus. Indian J Sci Technol 2012; 5: 2614-2618.
4. Gamal Hozayen W. Effect Of Hesperidin and Rutin On Doxorubicin Induced Testicular Toxicity in Male Rats. Int J Food Nutr Sci 2012; 1: 31-42.
5. Abdella EM, Ahmed R. Suppression of Doxorubicin Apoptotic, Histopathologic, Mutagenic and Oxidative Stress Effects in Male Mice Bone Marrow and Testis Tissues by Aqueous Rosemary Leaves Extract. Iran J Cancer Prev 2009; 2: 35-49.
6. Baumgartner A, Echmid TE, Cemeli E, Anderson D. Parallel evaluation of doxorubicin-induced genetic damage in human lymphocytes and sperm using the comet assay and spectral karyotyping. Mutagenesis 2004; 19: 313-318. [DOI:10.1093/mutage/geh032]
7. Hou MI, Chrysis D, Nurmio M, Parvinen M, Eksborg S, Soder O, et al. Doxorubicin Induces Apoptosis in Germ Line Stem Cells in the Immature Rat Testis and Amifostine Cannot Protect against This Cytotoxicity. Cancer Res 2005; 65: 9999-10005. [DOI:10.1158/0008-5472.CAN-05-2004]
8. Saalu LC, Osinubi AA, Olagunju JA. Early and Delayed Effects of Doxorubicin on Testicular Oxidative Status and Spermatogenesis in Rats. Int J Cancer Res 2010; 6: 1-9. [DOI:10.3923/ijcr.2010.1.9]
9. Brilhante O, Okada FK, Sasso-Cerri E, Stumpp T, Miraglia SM. Late morfofunctional alterations of the Sertoli cell caused by doxorubicin administered to prepubertal rats. Reprod Biol Endocrin 2012; 10:79-86. [DOI:10.1186/1477-7827-10-79]
10. Said G, Guilbert M, Morjani H, Garnotel R, Jeannesson P, El Btaouri H. Extracellular matrix proteins modulate antimigratory and apoptotic effects of Doxorubicin. Chemother Res Pract 2012; 2012: 268681. [DOI:10.1155/2012/268681]
11. Patil L, Balaraman R. Effect of Melatonin on Doxorubicin Induced Testicular Damage in Rats. Int J Pharm Tech Res 2009; 1: 879-884.
12. Malekirad AA, Hosseini N, Bayrami M, Hashemi T, Rahzani K, Abdollahi M. Benefit of Lemon Verbena in healthy subjects; targeting diseases associated with oxidative stress. Asian J Anim Vet Adv 2011; 6: 953-957. [DOI:10.3923/ajava.2011.953.957]
13. Abdel-Wahab MH, El-Mahdy MA, Abd-Ellah MF, Helal GK, Khalifa F, Hamadaa FMA. Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart. Pharmacol Res 2003; 48: 461-465. [DOI:10.1016/S1043-6618(03)00214-7]
14. Powell SR. Zinc and Health: Current Status and Future Directions, the Antioxidant Properties of Zinc. Nutr 2000; 130: 1447S-1454S. [DOI:10.1093/jn/130.5.1447S]
15. Dani V, Dhawan DK. Radioprotective role of zinc following single dose radioiodine exposure to red blood cells of rats. Indian J Med Res 2005; 122: 338-342.
16. Malekirad AA, Oryan Sh, Babapor V, Hashemi M, Fani A, Baeeri M, et al. Study on clinical and biochemical toxicity biomarkers in a zinc-lead mine workers. Toxicol Ind Health 2010; 26: 331-337. [DOI:10.1177/0748233710365697]
17. Ebisch IMW, Thomas CMG, Peters WHM, Braat DDM, Steegers-Theunissen RPM. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update 2007; 13: 163-174. [DOI:10.1093/humupd/dml054]
18. Dawei AI, Zhisheng W, Angu Z. Protective Effects of Nano-ZnO on the Primary Culture Mice Intestinal Epithelial Cells in in vitro Against Oxidative Injury. Int J Nanotechnol App 2009; 3: 1-6.
19. Medina C, Santos-Martinez MJ, Radomski A, Corrigan OI, Radomski MW. Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 2007; 150: 552-558. [DOI:10.1038/sj.bjp.0707130]
20. Singh Suri S, Fenniri H, Singh B. Nanotechnology-based drug delivery systems. J Occup Med Toxicol 2007; 2: 16. [DOI:10.1186/1745-6673-2-16]
21. Wang B, Feng W, Wang M, Wang TC, Gu Y, Zhu Motao, et al. Acute toxicological impact of nano- and submicro-scaled zinc oxide powder on healthy adult mice. J Nanopart Res 2008; 10: 263-276. [DOI:10.1007/s11051-007-9245-3]
22. Chang HJ, Choi SW, Ko S, Chun HS. Effect of Particle Size of Zinc Oxides on Cytotoxicity and Cell Permeability in Caco-2 Cells. J Food Sci Nutr 2011; 16: 174-178. [DOI:10.3746/jfn.2011.16.2.174]
23. Wang B, Feng W, Wang TC, Jia G, Wang M, Shi JW. Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. Toxicol Lett 2006; 161: 115-123. [DOI:10.1016/j.toxlet.2005.08.007]
24. Esterabeur H, Cheeseman K. Determination of alde-hyids lipid peroxidation products: malondealdhyde and 4-hydroxyl nonenal. Methods Enzymol 1990; 186: 407-421. [DOI:10.1016/0076-6879(90)86134-H]
25. Benzi IF, Strain S. Ferric reducing antioxidant assay. Methods Enzymol 1999; 292: 15-27.
26. Rezvanfar MA, Sadrkhanlou RA, Ahmadi A, Shojaei-Sadee H, Rezvanfar MA, 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 Exper Tox 2008; 27: 901-910. [DOI:10.1177/0960327108102046]
27. Wyrobek AJ, Gordon LA, Burkhart JG, Francis MW, Kapp Jr, Letz G, et al. An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 1983; 115: 1-72. [DOI:10.1016/0165-1110(83)90014-3]
28. 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.
29. Sohrabi D, Alipour M, Awsat Mellati A. Effect of Metronidazole on Spermatogenesis, Plasma Gonadotrophins and Testosterone in Male Rats. Iran J Pharm Res 2007; 6: 279-283.
30. Brilhante O, Stumpp T, Miraglia SM. Long-term testicular toxicity caused by doxorubicin treatment during pre-pubertal phase. Int J Med Sci 2011; 3: 52-60.
31. Ait Hamadouche N, Slimani M, Merad-Boudia B, Zaoui C. Reproductive Toxicity of Lead Acetate in Adult Male Rats. Am J Sci Res 2009; 3: 38-50.
32. Kovacs M, Schally AV, Nagy A, Koppan M, Groot K. Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone- releasing hormone. Proc Natl Acad Sci 1997; 94: 1420-1425. [DOI:10.1073/pnas.94.4.1420]
33. Atessahin A, Turk G, Karahan I, Yolmaz S, Ceribasi AO, Bulmus O. Lycopene prevents adriamycin-induced testicular toxicity in rats. Fertil Steril 2006; 85:1216-1222. [DOI:10.1016/j.fertnstert.2005.11.035]
34. Yeh YC, Liu TJ, Wang LC, Lee HW, Ting CT. A standardized extract of Ginkgo Biloba suppresses doxorubicin-induced oxidative stress and p53-mediated mitochondrial apoptosis in rat testes. Br J Pharmacol 2009; 156: 48-61. [DOI:10.1111/j.1476-5381.2008.00042.x]
35. Asmis R, Qiao M, Rossi RR, Cholewa J, Xu L, Asmis LM. Adriamycin promotes macrophage dysfunction in mice. Free Rad Biol Med 2006; 41: 165-174. [DOI:10.1016/j.freeradbiomed.2006.03.027]
36. Howell SJ, Shalet SM. Testicular function following chemotherapy. Hum Reprod 2001; 7: 363-369. [DOI:10.1093/humupd/7.4.363]
37. Hrdina R, Gersl V, Klimtova I, SimunekT, Mach J, Adamcova M. Anthracycline-induced cardiotoxicity. Acta Medica 2000; 43: 75-82.
38. Ichihara S, Yamada Y, Kawai Y, Osawa T, Furuhashi K, Duan Z, et al. Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity. Biochem Biophys Res Com 2007; 359: 27-33. [DOI:10.1016/j.bbrc.2007.05.027]
39. Kalender Y, Yel M, Kalender S. Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The effects of vitamin E and catechin. Toxicology 2005; 209: 39-45. [DOI:10.1016/j.tox.2004.12.003]
40. Saalu LC, Osinubi AA, Oguntola JA, Adeneye IO, Benebo AS. The Delayed Testicular Morphologic Effects of Doxorubicin and the Rejuvinating Role of Grapefruit Seed Extract. Int J Pharm 2010; 6: 192-199. [DOI:10.3923/ijp.2010.192.199]
41. Favier AE. The role of zinc in reproduction, Hormonal mechanisms. Biol Trace Elem Res 1992; 32: 363-382. [DOI:10.1007/BF02784623]
42. Freedman LP. Anatomy of the steroid receptor zinc finger region. Endocr Rev 1992; 13: 129-145. [DOI:10.1210/edrv-13-2-129]
43. Fuse H, Kazama T, Ohta S, Fujiuchi Y. Relationship between Zinc Concentrations in Seminal Plasma and Various Sperm Parameters. Int Urol Nephrol 1999; 3: 401-408. [DOI:10.1023/A:1007190506587]
44. Bray TM, Bettger WJ. The physiological role of zinc as an antioxidant. Free Radic Biol Med 1990; 8: 281-291. [DOI:10.1016/0891-5849(90)90076-U]
45. Zago MP, Oteiza PI. The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 2001; 31: 266-274. [DOI:10.1016/S0891-5849(01)00583-4]
46. Bagchi D, Vuchetich PJ, Bagchi M, Tran MX, Krohn RL, Ray SD, et al. Protective effects of zinc salts on TPA-induced hepatic and brain lipid peroxidation, glutathione depletion, DNA damage and peritoneal macrophage activation in mice. Gen Pharmacol 1998; 30: 43-50. [DOI:10.1016/S0306-3623(97)00072-4]
47. Sunderman FW. The influence of zinc on apoptosis. Ann Clin Lab Sci 1995; 25: 134-142.
48. Chimienti F, Aouffen M, Favier A, Seve M. Zinc homeostasis-regulating proteins: new drug targets for triggering cell fate. Curr Drug Targets 2003; 4: 323-338. [DOI:10.2174/1389450033491082]
49. Lina T, Fenghua Z, Huiying R, Jianyang J, Wenli L. Effects of Nano-zinc Oxide on Antioxidant Function in Broilers. Chin J Anim Nutr 2009; 21: 534-539.
50. Sharma V, Singh P, Pandey AK, Dhawan A. Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res 2012; 745: 84-91. [DOI:10.1016/j.mrgentox.2011.12.009]
51. Rasheed NA, Abdel Baky NA, Shebly W, Ahmed AM, Faddah LM. Effect of vitamin E and α-lipoic acid on nano zinc oxide induced renal cytotoxicity in Rats. Afr J Pharm Pharmacol 2012; 6: 2211-2223.
52. Yin Y, Lin Q, Sun H, Chen D, Wu Q, Chen X, et al. Cytotoxic effects of ZnO hierarchical architectures on RSC96 Schwann cells. Nanoscale Res Lett 2012; 7: 439-446. [DOI:10.1186/1556-276X-7-439]
53. Kim YH, Fazlollahi F, Kennedy IM, Yacobi N, Hamm-Alvarez SF. Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure. Am J Respir Crit Care Med 2010; 182: 1398-1409. [DOI:10.1164/rccm.201002-0185OC]
54. Says CM, Reed KL, Warheit DB. Assessing Toxicity of Fine and Nanoparticles: Comparing In Vitro Measurements to In Vivo Pulmonary Toxicity Profiles. Toxicol Sci 2007; 97: 163-180. [DOI:10.1093/toxsci/kfm018]
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