ROLE OF VITAMIN E (α TOCOPHEROL) TO PREVENT THE SPERMATOGONIA, SERTOLI CELL, AND LEYDIG CELL DAMAGE IN RATS TESTICLE (STRAIN WISTAR) AFTER CISPLATIN TREATMENT

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Published 2019-07-02
Rahmad Krismantoro Fikri Rizaldi Doddy M Soebadi

Abstract

Objective: To determine the difference in spermatogonium cells, leydig cells and sertoli cells count in white rats testicle (wistar strains) obtained with the combination of cisplatin and vitamin E compared with that only received cisplatin. Material & Methods: There were 4 random groups out of a total of twenty four winstar strain rats (n=6). The control group (I) injected normal saline 0.9% intraperitoneally (i.p.) as the placebo on the 3rd week. Group (II) given cisplatin (5 mg/kgbw) injection i.p. on 3rd week, Group (III) given cisplatin injection 5 mg/kgbw i.p. on 3rd week + vitamin E 50 mg/kgbw by gavage for 7 weeks and group (IV) cisplatin injection 5mg/kgbw i.p. on 3rd week + vitamin E 200 mg/kgbw by gavage for 7 weeks. Vitamin E was given 3 weeks before up to 4 weeks after cisplatin injection (total 7 weeks). Observations by calculating the average number of spermatogonia, sertoli and leydig cells on a cross-sectional section of the seminiferous tubule with Haematoxylin-Eosin staining using a 400x light magnification microscope. Results: Cisplatin decreases spermatogonia, sertoli, and leydig cells significantly against control. Vitamin E 200 mg/kgbw significantly increased the number of spermatogonium, sertoli, and leydig cells (p<0.05) compared to group in combination with vitamin E 50 mg/kg bw and cisplatin or cisplatin only group. Only leydig cells count was significantly increased in the combination group of vitamin E 50 mg/kgbw  and cisplatin compared to the cisplatin group. Conclusion: Vitamin E 200 mg/kgbw provides a protective effect against decreased spermatogonia, sertoli and leydig cells due to cisplatin 5 mg/kgbw exposure which its protectivity depends on the given dose.


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Keywords

vitamin e, spermatogonium cells, sertoli cells, leydig cells, cisplatin

References

Steliarova-Foucher E, Stiller C, Kaatsch P, Berrino F, Coebergh JW, ACCIS Scientific Committee. Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study. Lancet. 2004; 364: 2097–105.

Bieber AM, Marcon L, Hales BF, Robaire B. Effects of chemotherapeutic agents for testicular cancer on the male rat reproductive system, spermatozoa, and fertility. Journal of Andrology. 2006; 2(27): 189-200.

Bower M, Newlands ES, Holden L, Rustin GJ, Begent RH. Treatment of men with metastatic non-seminomatous germ cell tumours with cyclical POMB/ACE chemotherapy. Ann Oncol. 1997; 8: 477–83.

Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin and either vinblastine or etoposide. N Engl J Med. 1987; 316: 1435–40.

Attesahin A, Karahan I, Turk G, Gur S, Yilmaz S, Ceribasi AO. Protective role of lycopene on cisplatin-induced changes in sperm characteristics, testicular damage, and oxidative stress in rats. Reproductive Toxicology. 2006; 21: 42-47.

Drasga R, Einhorn L, Williams S, Patel D, Stevens E. Fertility after chemotherapy for testicular cancer. Journal of Clinical Oncology. 1983; 1(3): 179-83.

Pont J, Albrecht W. Fertility after chemotherapy for testicular germ cell cancer. Fertil Steril. 1997; 68: 1–5.

DeSantis M, Albrecht W, Holtl W, Pont J. Impact of cytotoxic treatment on long-term fertility in patients with germ-cell cancer. Int J Cancer. 1999; 83: 864– 5.

Hansen SW, Berthelsen JG, von der Masse H. Long-term fertility and leydig cell function in patients treated for germ cell cancer with cisplatin, vinblastine, and bleomycin versus surveillance. J Clin Oncol. 1990; 8: 1695–8.

Halliwell B, Gutteridge JMC. Free radicals in biology and medicine, 4th Ed. Oxford University Press. New York: USA; 2007.

Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2008; 59: 2–11.

Agarwal A, Said TM. Oxidative stress, DNS damage, and apoptosis in male infertility. BJU International. 2005: 95

Cherry SM, Hunt PA, Hassold TJ. Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination or chromosome segregation. Mutat Res. 2004; 564(2): 115–28.

Meistrich ML, Finch M, da Cunha MF, Hacker U, Au WW. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res. 1982; 42(1): 122–31.

Martins NM, Santos NA, Curti C, Bianchi ML, Santos AC. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol. 2008; 28(3): 337–44.

Soni KK, Kim HK, Choi BR, Karna KK, You JH, Cha JS, et al. Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress. Drug Des Devel Ther. 2016; 10: 3959–68.

Uzunhisarcikli M, Kalender Y. Protective effects of vitamins C and E against hepatotoxicity induced by methyl parathion in rats. Ecotoxicol Environ Saf. 2011; 74: 2112-8.

Dahlan S. Statistik untuk kedokteran dan kesehatan:uji hipotesis. Jakarta: Bina Mitra Press; 2006.

Colpi GM, Contalbi GF, Nerva F, Sagone P, Piediferro G. Testicular function following chemo-radiotherapy. Eur J Obstet Gynecol Reprod Biol. 2004; 113(Suppl 1): S2-6.

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; 47: 194-208.

Ciftci O, Beytur A, Cakir O, Gurbuz N, Vardi N. Comparison of reproductive toxicity caused by cisplatin and Novel Platinum-N-Heterocyclic carbene complex in male rats. Basic & Clinical Pharmacology & Toxicology. 2011; 109: 328–33.

Sanocka D, Kurpisz M. Reactive oxygen species and sperm cells. Reproductive Biology and Endocrinology. 2004; 2: 12.

Huang Q, Dunn RT, Jayadev S, DiSorbo O, Pack FD, Farr SB, et al. Assessment of cisplatin-induced nephro-toxicity by microarray technology. Toxicol Sci. 2001; 63: 196–207.

Atasayar S, Gürer-Orhan H, Orhan H, Gurel B, Girgin G, Ozgunes H. Preventive effect of aminoguanidine compared to vitamin E and C on cisplatin-induced nephrotoxicity in Rats. Exp Toxicol Pathol. 2009; 61: 23–32.

Ganga UK, Kishori B, Reddy PS. Cisplatin and/or etoposide induces oxidative stress in testicular, hepatic and kidney tissues in male albino mice. Journal of Biology and Earth Sciences. 2013; 3(2): B249-54.

Kaminski R, Darbinyan A, Merabova N, Deshmane SL, White MK, Khalili K. Protective role of Purα to Cisplatin. Cancer Biol Ther. 2008; 7: 1926–35.

Kaya K, Ciftci O, Cetin A, Dogan H, Basak N. Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia. 2015; 47: 793-800.

Satoh M, Kashihara N, Fujimoto S, Horike H, Tokura T, Namikoshi T, et al. A novel free radical scavenger, edarabone, protects against cisplatin induced acute renal damage in vitro and in vivo. J Pharmacol Exp Ther. 2003; 305: 1183-90.

Brozovic A, Ambriović-Ristov A, Osmak M. The relationship between cisplatin induced reactive oxygen species, glutathione and BCL-2 and resistance to cisplatin. Crit Rev Toxicology. 2010; 40: 347-59.

Gunawan SG. Farmakologi dan Terapi, 5th Ed. Jakarta: FKUI. 2007; 786-787.

Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol. 2010; 80: 1613-31.

Gevrek F, Erdemir F. Investigation of the effects of curcumin, Vit-E and their combination in cisplatin-induced testicular apoptosis using immunohistochemical technique. Turk J Urol. 2018; 44(1): 16-23.

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Department of Urology, Faculty of Medicine/Airlangga University