EFFECT OF VITAMIN E (α TOCOPHEROL) ADMINISTRATION ON APOPTOSIS OF GERMINAL CELLS EPITHELIUM TESTIS IN SPRAGUE DAWLEY WHITE STRAIN RATS AFTER EXPOSED BY CISPLATIN
Objective: To determine the differences of germinal epithelial testicular cell apoptosis in white Sprague Dawley strain rat that received combination of cisplatin and vitamin E compared to Sprague Dawley strain rat that received cisplatin only. Material & Methods: Twenty four Sprague Dawley rats were divided into 4 groups randomly. Group 1 Negative Control (NC) was given an injection of 1 cc 0.9% normal saline intraperitoneally as a placebo, group 2 Positive Control (PC) was given 5 mg/kgBW cisplatin intraperitoneally, group 3 (P1) was given cisplatin injection 5 mg/kgBW intraperitoneally + vitamin E (α tocopherol) 50 mg/kgBW by gavage and group 4 (P2) was given cisplatin injection 5 mg/kgBW intraperitoneally + vitamin E (α tocopherol) 200 mg/kgBW by gavage. Vitamin E (α tocopherol) was given 3 weeks before up to 4 weeks after cisplatin injection. Observation of the germinal epithelial cells apoptosis was carried out by calculating germinal epithelial cells apoptosis in the cross-section preparations of the seminiferous tubule which gave a positive reaction to the apoptag staining, using a 400x magnification light microscope. Results: Apoptosis on positive control (PC) group was different significantly compared to the negative control (NC) group (p<0.05). There was a significant difference in the apoptosis of germinal epithelial testicular cells in the cisplatin + vitamin E 50 mg/kgBW compared to the PC group (p<0.05). The cisplatin + vitamin E 200 mg/kgBW group; had a lower number of apoptosis compared to the cisplatin + vitamin E 50 mg/kgBW (p<0.05). Conclusion: Vitamin E provides a protective effect on decreasing the amount of apoptosis due to cisplatin exposure. The protective effect of vitamin E is dose-dependent.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5): E359–86.
Sadeghi M, Ghoncheh M, Mohammadian-Hafshejani A, Gandomani HS, Rafiemanesh H, Salehiniya H. Incidence and mortality of testicular cancer and relationships with development in Asia. Asian Pac J Cancer Prev. 2016; 17(9): 4251–7.
Seaman F, Sawhney P, Giammona CJ, Richburg JH. Cisplatin-induced pulse of germ cell apoptosis precedes long-term elevated apoptotic rates in C57/BL/6 mouse testis. Apoptosis. 2003; 8(1): 101–8.
Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: An update. Am J Reprod Immunol. 2008; 59(1): 2–11.
Gevrek F, Erdemir F. Investigation of the effects of curcumin, vitamin E and their combination in cisplatin-induced testicular apoptosis using immunohistochemical technique. Türk Üroloji Dergisi/Turkish J Urol. Jan 2018; 44(1): 16–23.
Uzunhisarcikli M, Kalender Y. Protective effects of vitamins C and E against hepatotoxicity induced by methyl parathion in rats. Ecotoxicol Environ Saf. 2011; 74(7): 2112–8.
Mohammadnejad D, Abedelahi A, Soleimani-rad J, Mohammadi-Roshandeh A, Rashtbar M, Azami A. Degenerative effect of cisplatin on testicular germinal epithelium. Adv Pharm Bull. 2012; 2(2): 173–7.
X Zhang, N Yamamoto, S Soramoto. Cisplatin-induced germ cell apoptosis in mouse testes. Arch Androl. 2001; 46(1): 43–9.
Desoize B, Madoulet C. Particular aspects of platinum compounds used at present in cancer treatment. Critical Reviews in Oncology/Hematology. 2002; 42: 317–25.
Shah N, Dizon DS. New-generation platinum agents for solid tumors. Futur Oncol. 2009; 5(1): 33–42.
Türk G, Ateşşahin A, Sönmez M, Çeribaşi AO, Yüce A. Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril; 2008.
Rahmad Krismantoro, Fikri Rizaldi, I Ketut Sudiana, Doddy M Soebadi. Effect of vitamin e (α tocopherol) administration to prevent spermatogonium, sertoli, and leydig cell damages on rats testis (wistar strain) after cisplatin treatment; 2017
Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Pérez JM. Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem. 2007; 7(1): 3–18.
Barabas K, Milner R, Lurie D, Adin C. Cisplatin: A review of toxicities and therapeutic applications. Veterinary and Comparative Oncology. 2008; 6: 1–18.
Cai L, Hales BF, Robaire B. Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol Reprod; 1997.
Kaminski R, Darbinyan A, Merabova N, Deshmane SL, White MK, Khalili K. Protective role of Purα to cisplatin. Cancer Biol Ther; 2008.
Anand H, Misro MM, Sharma SB, Prakash S. Protective effects of eugenia jambolana extract versus N-acetyl cysteine against cisplatin-induced damage in rat testis. Andrologia; 2015.
Meistrich ML, Finch M, Cunha MF, Hacker U, Au WW. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells damaging effects of fourteen chemotherapeutic drugs on mouse testis. Jan 1982; 42: 122–31.
Cherry SM, Hunt PA, Hassold TJ. Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination or chromosome segregation. Mutat Res - Genet Toxicol Environ Mutagen. Dec 2004; 564(2): 115–28.
Martins N, Santos N, Curti C, Bianchi L, Santos A. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol. October 2008; 28: 608–20.
Ateşşahin A, Şanna E, Türk G, Çeribaşi AO, Yilmaz S, Yüce A, et al. Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res; 2006.
Ateşşahin A, Karahan I, Türk G, Gür S, Yilmaz S, Çeribaşi AO. Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage and oxidative stress in rats. Reprod Toxicol. 2006; 21(1): 42–7.
Combs Jr GF. Vitamin fundamental aspect in nutrition, 3rd Ed. New York: Elsevier; 2008.
Ingold KU, Webb AC, Witter D, Burton GW, Metcalfe TA, Muller DPR. Vitamin E remains the major lipid-soluble, chain-breaking antioxidant in human plasma even in individuals suffering severe vitamin E deficiency. Arch Biochem Biophys; 1987.
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.