International Journal of
Reproductive Biomedicine
Thu, Apr 25, 2024
[Archive]
Volume 17, Issue 4 (April 2019 2019)
IJRM 2019, 17(4): 245-252 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Kaya C, Barbaros Baseskioglu A, Yigitaslan S, Yasemin Ozatik F, Ozatik O, Uslu S. The therapeutic potential of amifostine on cyclophosphamide-induced testicular dysfunction in rats: An experimental study. IJRM 2019; 17 (4) :245-252
URL: http://ijrm.ir/article-1-1491-en.html
URL: http://ijrm.ir/article-1-1491-en.html
Coskun Kaya * 
1, Ali Barbaros Baseskioglu2 , Semra Yigitaslan3 , Fikriye Yasemin Ozatik4 , Orhan Ozatik5 , Sema Uslu6
1, Ali Barbaros Baseskioglu2 , Semra Yigitaslan3 , Fikriye Yasemin Ozatik4 , Orhan Ozatik5 , Sema Uslu6
1- Department of Urology, Eskisehir City Hospital, Eskisehir, Turkey , coskun_kaya2008@ yahoo.com
2- Department of Urology, Eskisehir Acibadem Hospital, Eskisehir, Turkey
3- Department of Pharmacology, Eskisehir Osmangazi University, Eskisehir, Turkey
4- Department of Pharmacology, Kutahya Health Sciences University, Kutahya, Turkey
5- Department of Histology and Embryology, Kutahya Health Sciences University, Kutahya, Turkey
6- Department of Biochemistry, Eskisehir Osmangazi University, Eskisehir, Turkisehir Osmangazi University, Eskisehir, Turkey
2- Department of Urology, Eskisehir Acibadem Hospital, Eskisehir, Turkey
3- Department of Pharmacology, Eskisehir Osmangazi University, Eskisehir, Turkey
4- Department of Pharmacology, Kutahya Health Sciences University, Kutahya, Turkey
5- Department of Histology and Embryology, Kutahya Health Sciences University, Kutahya, Turkey
6- Department of Biochemistry, Eskisehir Osmangazi University, Eskisehir, Turkisehir Osmangazi University, Eskisehir, Turkey
Abstract: (2541 Views)
Background: Cyclophosphamide (CP) is a well-known alkylating anticancer agent used in the treatment of various malignant and non-malignant tumors. CP may also cause a variety of adverse effects, including reproductive toxicity. Amifostine is known as a cytoprotective drug having antioxidant properties.
Objective: To evaluate the possible beneficial effects of amifostine on testicular toxicity induced by CP in rats.
Materials and Methods: A total of 35 Sprague-Dawley rats were used in this experimental study. The CP group animals received a single dose of 200 mg/kg CP on Day 8 by intraperitoneal injection and were left untreated for the following seven days. The two remaining groups of animals were treated with 200 mg/kg/day amifostine (AMF 200) and 400 mg/kg/day amifostine (AMF 400) for seven days prior to and following a single intraperitoneal injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels were measured in serum using commercial ELISA kits. The epidydimal sperm count was determined.
Results: The tubular epithelial height in the testis was significantly higher in the AMF400 group compared to other groups (p < 0.001). Animals in the AMF400 group showed minimal debris in the tubules, no Sertoli cell damage, and the Johnsen scores were slightly higher in the AMF400 group. The epididymal sperm count was significantly lower in the CP-administered animals compared to the control animals and was significantly higher in the AMF200 and AMF400 groups compared to the CP group (p = 0.006, and p = 0.019 respectively).
Conclusion: Amifostine, at a dose of 400 mg/kg, may have a protective effect on testicular damage induced by CP in rats.
Objective: To evaluate the possible beneficial effects of amifostine on testicular toxicity induced by CP in rats.
Materials and Methods: A total of 35 Sprague-Dawley rats were used in this experimental study. The CP group animals received a single dose of 200 mg/kg CP on Day 8 by intraperitoneal injection and were left untreated for the following seven days. The two remaining groups of animals were treated with 200 mg/kg/day amifostine (AMF 200) and 400 mg/kg/day amifostine (AMF 400) for seven days prior to and following a single intraperitoneal injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels were measured in serum using commercial ELISA kits. The epidydimal sperm count was determined.
Results: The tubular epithelial height in the testis was significantly higher in the AMF400 group compared to other groups (p < 0.001). Animals in the AMF400 group showed minimal debris in the tubules, no Sertoli cell damage, and the Johnsen scores were slightly higher in the AMF400 group. The epididymal sperm count was significantly lower in the CP-administered animals compared to the control animals and was significantly higher in the AMF200 and AMF400 groups compared to the CP group (p = 0.006, and p = 0.019 respectively).
Conclusion: Amifostine, at a dose of 400 mg/kg, may have a protective effect on testicular damage induced by CP in rats.
Type of Study: Original Article |
References
1. [1] Tripathi DN, Jena GB. Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology 2008; 248: 96-103. [DOI:10.1016/j.tox.2008.03.015]
2. [2] Charak BS, Gupta R, Mandrekar P, Sheth NA, Banavali SD, Saikia TK, et al. Testicular dysfunction after cyclophosphamide-vincristine-procarbazineprednisolone chemotherapy for advanced Hodgkin's disease. A long-term follow-up study. Cancer 1990; 65:1903-1906.
https://doi.org/10.1002/1097-0142(19900501)65:9<1903::AID-CNCR2820650905>3.0.CO;2-# [DOI:10.1002/1097-0142(19900501)65:93.0.CO;2-#]
3. [3] Motawi TM, Sadik NA, Refaat A. Cytoprotective effects of DL-alpha-lipoic acid or squalene on cyclophosphamideinduced oxidative injury: an experimental study on rat myocardium, testicles and urinary bladder. Food Chem Toxicol 2010; 48: 2326-2336. [DOI:10.1016/j.fct.2010.05.067]
4. [4] Oyagbemi AA, Omobowale TO, Saba AB, Adedara IA, Olowu ER, Akinrinde AS, et al. Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats. Andrologia 2016; 48: 393-401. [DOI:10.1111/and.12459]
5. [5] Abd El Tawab AM, Shahin NN, AbdelMohsen MM. Protective effect of Saturejamontana extract on cyclophosphamide-induced testicular injury in rats. Chem Biol Interact 2014; 224: 196-205. [DOI:10.1016/j.cbi.2014.11.001]
6. [6] Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril 2003; 79: 829-843. [DOI:10.1016/S0015-0282(02)04948-8]
7. [7] Griveau JF, Le Lannou D. Influence of oxygen tension on reactive oxygen species production and human sperm function. Int J Androl 1997; 20: 195-200. [DOI:10.1046/j.1365-2605.1997.00049.x]
8. [8] Liu F, Li XL, Lin T, He DW, Wei GH, Liu JH, et al. The cyclophosphamide metabolite, acrolein, induces cytoskeletal changes and oxidative stress in Sertoli cells. Mol Biol Rep 2012; 39: 493-500. [DOI:10.1007/s11033-011-0763-9]
9. [9] Yigitaslan S, Ozatik O, Ozatik FY, Erol K, Sirmagul B, Baseskioglu AB. Effects of tadalafil on hemorrhagic cystitis and testicular dysfunction induced by cyclophosphamide in rats. Urol Int 2014; 93: 55-62. [DOI:10.1159/000352095]
10. [10] Block KI, Gyllenhaal C. Commentary: the pharmacological antioxidant amifostine - implications of recent research for integrative cancer care. Integr Cancer Ther 2005; 4: 329- 351. [DOI:10.1177/1534735405282842]
11. [11] Stankiewicz A, Skrzydlewska E. Amifostine-antioxidant drug in anticancer therapy. Toxicol Mech Methods 2006; 16: 181-188. [DOI:10.1080/15376520500195608]
12. [12] Jahnukainen K, Jahnukainen T, Salmi TT, Svechnikov K, Eksborg S, Söder O. Amifostine protects against early but not late toxic effects of doxorubicin in infant rats. Cancer Res 2001; 61: 6423-6427.
13. [13] Hou M, Chrysis D, Nurmio M, Parvinen M, Eksborg S, Söder 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]
14. [14] 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: 3-13. [DOI:10.1186/1477-7827-8-3]
15. [15] Lirdi LC, Stumpp T, Sasso-Cerri E, Miraglia SM. Amifostine protective effect on cisplatin-treated rat testis. Anat Rec (Hoboken) 2008; 291: 797-808. [DOI:10.1002/ar.20693]
16. 16] Andrieu MN, Kurtman C, Hicsonmez A, Ozbilgin K, Eser E, Erdemli E. In vivo study to evaluate the protective effects of amifostine on radiation-induced damage of testis tissue. Oncology 2005; 69: 44-51. [DOI:10.1159/000087475]
17. [17] Johnsen SG. Testicular biopsy score count a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1970; 1: 2-25. [DOI:10.1159/000178170]
18. [18] Weiss JF. Pharmacologic approaches to protection against radiation-induced lethality and other damage. Environ Health Perspect 1997; 105: 1473-1478. [DOI:10.1289/ehp.97105s61473]
19. [19] Nalca AM, Kurtman C, Hicsonmez A, Ozbilgin K, Eser E, Erdemli E. In vivo study to evaluate the protective effects of amifostine on radiation-induced damage of testis tissue. Oncology 2005; 69: 44-51. [DOI:10.1159/000087475]
20. [20] Golkar-Narenji A, Berakati Z, Eimani H, Shabani F, Gourabi H. The influence of amifostine administration prior to cyclophosphamide on in vitro maturation of mouse oocytes. J Assist Reprod Genet 2013; 30: 939-944. [DOI:10.1007/s10815-013-0035-9]
21. [21] Koyama H, Wada T, Nishizawa Y, Iwanaga T, Aoki Y. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer 1977; 39: 1403-1409.
https://doi.org/10.1002/1097-0142(197704)39:4<1403::AID-CNCR2820390408>3.0.CO;2-8 [DOI:10.1002/1097-0142(197704)39:43.0.CO;2-8]
22. [22] Savoye C, Swenberg C, Hugot S, Sy D, Sabattier R, Charlier M, et al. Thiol WR-1065 and disulphide WR-33278, two metabolites of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage. Int J Radiat Biol 1997; 71: 193-202. [DOI:10.1080/095530097144319]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
