World J Mens Health.  2019 May;37(2):249-256. 10.5534/wjmh.180105.

Protective Effect of All-Trans Retinoic Acid in Cisplatin-Induced Testicular Damage in Rats

Affiliations
  • 1Department of Urology, Tepecik Training and Research Hospital, Izmir, Turkey. meclecuy@hotmail.com
  • 2Department of Medical Biochemistry, Tepecik Training and Research Hospital, Izmir, Turkey.
  • 3Department of Pathology, Tepecik Training and Research Hospital, Izmir, Turkey.
  • 4Department of Internal Medicine, Tepecik Training and Research Hospital, Izmir, Turkey.

Abstract

PURPOSE
To investigate the effects of all-trans retinoic acid (ATRA) in cisplatin (CP)-induced testicular damage in rats.
MATERIALS AND METHODS
Twenty-eight male Wistar rats were divided into four groups: Control, ATRA alone, ATRA+CP, and CP alone. Body weight, testicular weight, sperm count, sperm motility, percentage of abnormal sperm, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in testicular tissue, and testicular histopathology were compared among groups.
RESULTS
The sperm count and motility significantly decreased and the percentage of abnormal sperm significantly increased in the CP group compared to the control and ATRA groups. CP+ATRA administration significantly increased the sperm count and motility, but reduced the abnormal sperm count. CP administration significantly increased TOS and OSI compared to the control group and the other groups. Administering CP+ATRA significantly decreased TOS and the OSI in testicular tissue and reduced spermatogenesis, but increased the Johnsen score.
CONCLUSIONS
The destructive effects of CP treatment on testicular tissue and spermatogenesis were reduced by administering ATRA.

Keyword

Cisplatin; Oxidative stress; Spermatogenesis; Testis; Vitamin A

MeSH Terms

Animals
Body Weight
Cisplatin
Humans
Male
Oxidative Stress
Rats*
Rats, Wistar
Sperm Count
Sperm Motility
Spermatogenesis
Spermatozoa
Testis
Tretinoin*
Vitamin A
Cisplatin
Tretinoin
Vitamin A

Figure

  • Fig. 1 Box graphics of sperm count (A), motility (B), and abnormal sperm rate (C). ATRA: all-trans retinoic acid, CP: cisplatin.

  • Fig. 2 Box graphics of total antioxidant status (TAS) (A), total oxidant status (TOS) (B), and oxidative stress index (OSI) (C). ATRA: all-trans retinoic acid, CP: cisplatin.

  • Fig. 3 Testicular histopathology in control group (A), all-trans retinoic acid+cisplatin (CP) group (B), and CP group (C) (A–C: H&E, ×400).


Reference

1. Adejuwon SA, Femi-Akinlosotu OM, Omirinde JO. Cisplatin-induced testicular dysfunction and its amelioration by Launaea taraxacifolia leaf extract. Andrologia. 2015; 47:553–559. PMID: 24919929.
2. Ilbey YO, Ozbek E, Cekmen M, Simsek A, Otunctemur A, Somay A. Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Hum Reprod. 2009; 24:1717–1725. PMID: 19279034.
Article
3. Ilbey YO, Ozbek E, Simsek A, Cekmen M, Otunctemur A, Somay A. Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats. J Androl. 2009; 30:505–514. PMID: 19234314.
4. Ciftci O, Cetin A, Aydin M, Kaya K, Oguz F. Fish oil, contained in eicosapentaenoic acid and docosahexaenoic acid, attenuates testicular and spermatological damage induced by cisplatin in rats. Andrologia. 2014; 46:1161–1168. PMID: 24350676.
Article
5. Tuglu D, Yuvanc E, Yilmaz E, Gencay IY, Atasoy P, Kisa U, et al. The antioxidant effect of dexmedetomidine on testicular ischemia-reperfusion injury. Acta Cir Bras. 2015; 30:414–421. PMID: 26108030.
Article
6. Salem EA, Salem NA, Maarouf AM, Serefoglu EC, Hellstrom WJ. Selenium and lycopene attenuate cisplatin-induced testicular toxicity associated with oxidative stress in Wistar rats. Urology. 2012; 79:1184.e1–1184.e6.
Article
7. Amory JK, Ostrowski KA, Gannon JR, Berkseth K, Stevison F, Isoherranen N, et al. Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study. Andrology. 2017; 5:1115–1123. PMID: 28980413.
Article
8. Elsayed AM, Abdelghany TM, Akool el-S, Abdel-Aziz AA, Abdel-Bakky MS. All-trans retinoic acid potentiates cisplatin-induced kidney injury in rats: impact of retinoic acid signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2016; 389:327–337. PMID: 26659823.
Article
9. Zuno-Floriano FG, Holstege D, Hengel MJ, Gaikwad NW, Aldana-Madrid ML, Miller MG. Determination of vitamin A and its metabolites in rat testis: possible involvement of vitamin A in testicular toxicity caused by molinate. Bull Environ Contam Toxicol. 2012; 88:1038–1042. PMID: 22456730.
Article
10. Rao J, Zhang C, Wang P, Lu L, Zhang F. All-trans retinoic acid alleviates hepatic ischemia/reperfusion injury by enhancing manganese superoxide dismutase in rats. Biol Pharm Bull. 2010; 33:869–875. PMID: 20460768.
Article
11. Ewees MG, Abdelghany TM, Abdel-Aziz AA, Abdel-Bakky MS. All-trans retinoic acid mitigates methotrexate-induced liver injury in rats; relevance of retinoic acid signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2015; 388:931–938. PMID: 25971792.
Article
12. Yokoi K, Uthus EO, Nielsen FH. Nickel deficiency diminishes sperm quantity and movement in rats. Biol Trace Elem Res. 2003; 93:141–154. PMID: 12835498.
Article
13. Sönmez M, Türk G, Yüce A. The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology. 2005; 63:2063–2072. PMID: 15823361.
Article
14. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004; 37:112–119. PMID: 14725941.
Article
15. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38:1103–1111. PMID: 16214125.
Article
16. Ilbey YO, Ozbek E, Simsek A, Otunctemur A, Cekmen M, Somay A. Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats. Fertil Steril. 2009; 92:1124–1132. PMID: 18829000.
Article
17. Johnson L, Petty CS, Neaves WB. The relationship of biopsy evaluations and testicular measurements to over-all daily sperm production in human testes. Fertil Steril. 1980; 34:36–40. PMID: 7398905.
Article
18. Kaya K, Ciftci O, Cetin A, Doğan H, Başak N. Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. Andrologia. 2015; 47:793–800. PMID: 25220503.
Article
19. van Beek ME, Meistrich ML. Spermatogenesis in retinol-deficient rats maintained on retinoic acid. J Reprod Fertil. 1992; 94:327–336. PMID: 1593535.
Article
20. Chung SS, Wolgemuth DJ. Role of retinoid signaling in the regulation of spermatogenesis. Cytogenet Genome Res. 2004; 105:189–202. PMID: 15237207.
Article
21. Hogarth CA, Griswold MD. The key role of vitamin A in spermatogenesis. J Clin Invest. 2010; 120:956–962. PMID: 20364093.
Article
22. van Pelt AM, de Rooij DG. Synchronization of the seminiferous epithelium after vitamin A replacement in vitamin A-deficient mice. Biol Reprod. 1990; 43:363–367. PMID: 2271719.
Article
23. Beytur A, Ciftci O, Oguz F, Oguzturk H, Yilmaz F. Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats. Cancer Chemother Pharmacol. 2012; 69:207–213. PMID: 21681572.
Article
24. Sikka SC. Relative impact of oxidative stress on male reproductive function. Curr Med Chem. 2001; 8:851–862. PMID: 11375755.
Article
25. Choudhury RC, Jagdale MB. Vitamin E protection from/potentiation of the cytogenetic toxicity of cisplatin in Swiss mice. J Chemother. 2002; 14:397–405. PMID: 12420859.
26. Giri A, Khynriam D, Prasad SB. Vitamin C mediated protection on cisplatin induced mutagenicity in mice. Mutat Res. 1998; 421:139–148. PMID: 9852988.
Article
27. Koksal M, Oğuz E, Baba F, Eren MA, Ciftci H, Demir ME, et al. Effects of melatonin on testis histology, oxidative stress and spermatogenesis after experimental testis ischemia-reperfusion in rats. Eur Rev Med Pharmacol Sci. 2012; 16:582–588. PMID: 22774397.
28. Sherif IO, Abdel-Aziz A, Sarhan OM. Cisplatin-induced testicular toxicity in rats: the protective effect of arjunolic acid. J Biochem Mol Toxicol. 2014; 28:515–521. PMID: 25130312.
Article
29. Moreb JS, Ucar-Bilyeu DA, Khan A. Use of retinoic acid/aldehyde dehydrogenase pathway as potential targeted therapy against cancer stem cells. Cancer Chemother Pharmacol. 2017; 79:295–301. PMID: 27942929.
Article
30. Tang XH, Gudas LJ. Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol. 2011; 6:345–364. PMID: 21073338.
Article
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