The protective effects of acetyl L-carnitine on testis gonadotoxicity induced by cisplatin in rats

The protective effects of acetyl L-carnitine on testis gonadotoxicity induced by cisplatin in rats

Background: Cisplatin, an effective antineoplastic agent, damages normal cells in a manner related to chemotherapy. Acetyl L-carnitine protects cells against mitochondrial and nuclear damage induced by chemotherapy. Aims: Animal experiment Study Design: The aim of this study was to examine the protective effects of acetyl L-carnitine on cisplatin-induced gonadotoxicity in testicular structures. Twenty-four male Wistar albino rats were divided into four Groups (n=6): Group 1 (control) was administered saline; Group 2 was administered acetyl L- carnitine; Group 3 was administered cisplatin; and Group 4 was pre-treated with acetyl L-carnitine before cisplatin administration. Methods: After 72hr of treatment with cisplatin, the rats were sacrificed, and the testicular tissues were removed. Morphometric, histomorphologic and immunohistochemical analyses were conducted. Results: At the end of the experiment, Group 3 was characterised by statistically significant weight loss, a degenerative appearance of the seminiferous tubules in the peripheral region, separation of spermatogenic cell series from the tubular wall, cellular debris in the lumen and central interstitial oedema. Sperm morphology appeared to be abnormal. Tubular diameter and wall thickness decreased, and the number of TUNEL- and active caspase-positive cells increased compared with the other Groups. The histological findings in Group 4 were better than those in Group 3. Conclusion: It was concluded that the prophylactic use of acetyl L-carnitine protects against cisplatin-induced testicular tissue damage.

___

  • 1. Sastry J, Kellie SJ. Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. Pediatr Hematol Oncol 2005;22:441-5.
  • 2. Beijers AJ, Jongen JL, Vreugdenhil G. Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies. Neth J Med 2012;70:18-25.
  • 3. Dohle GR. Male infertility in cancer patients: review of the literature. Int J Urol 2010;17:327-31.
  • 4. Jamieson ER, Lippard SJ. Structure, Recognition, and Processing of Cisplatin-DNA Adducts. Chem Rev 1999;99:2467-98.
  • 5. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003;22:7265-79.
  • 6. Nozaki Y, Furubo E, Matsuno T, Fukui R, Kizawa K, Kozaki T, et al. Collaborative work on evaluation of ovarian toxicity. 6) Two-or four-week repeated-dose studies and fertility study of cisplatin in female rats. J Toxicol Sci 2009;34 Suppl 1:SP73-81.
  • 7. 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 Clin Pharmacol Toxicol 2011;109:328-33.
  • 8. Boekelheide K. Mechanisms of toxic damage to spermatogenesis. J Natl Cancer Inst Monogr 2005;34:6-8.
  • 9. Zhang X, Yamamoto N, Soramoto S, Takenaka I. Cisplatin-induced germ cell apoptosis in mouse testes. Arch Androl 2001;46:43-9.
  • 10. Sawhney P, Giammona CJ, Meistrich ML, Richburg JH. Cisplatin- induced long-term failure of spermatogenesis in adult C57/Bl/6J mice. J Androl 2005;26:136-45.
  • 11. Mohamed J, Wei WL, Husin NN, Alwahaibi NY, Budin SB. Selenium supplementation reduced oxidative stress in diethylnitro- samine-induced hepatocellular carcinoma in rats. Pak J Biol Sci 2011;14:1055-60.
  • 12. Annadurai T, Vigneshwari S, Thirukumaran R, Thomas PA, Geraldine P. Acetyl-L-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats. J Physiol Biochem 2011;67:519-30.
  • 13. Arockia Rani PJ, Panneerselvam C. Carnitine as a free radical scavenger in aging. Exp Gerontol 2001;36:1713-26.
  • 14. Cetinkaya A, Bulbuloglu E, Kantarceken B, Ciralik H, Kurutas EB, Buyukbese MA, et al. Effects of L-carnitine on oxidant/antioxidant status in acetic acid-induced colitis. Dig Dis Sci 2006;51:488-94.
  • 15. Tufekci O, Gunes D, Ozogul C, Kolatan E, Altun Z, Yilmaz O, et al. Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity. Chemotherapy 2009;55:451-9.
  • 16. Gunes D, Kirkim G, Kolatan E, Guneri EA, Ozogul C, Altun Z, et al. Evaluation of the effect of acetyl L-carnitine on experimental cisplatin ototoxicity and neurotoxicity. Chemotherapy 2011;57:186-94.
  • 17. Calò LA, Pagnin E, Davis PA, Semplicini A, Nicolai R, Calvani M, et al. Antioxidant effect of L -carnitine and its short chain esters: relevance for the protection from oxidative stress related cardiovascular damage. Int J Cardiol 2006;107:54-60.
  • 18. Ng CM, Blackman MR, Wang C, Swerdloff RS. The role of carnitine in the male reproductive system. Ann N Y Acad Sci 2004;1033:177-88.
  • 19. Jeulin C, Lewin LM. Role of free L-carnitin and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update 1996;2:87-102.
  • 20. Yeste M, Sancho S, Briz M, Pinart E, Bussalleu E, Bonet S. A diet supplemented with L-carnitine improves the sperm quality of Pietrain but not of Duroc and Large White boars when photope- riod and temperature increase. Theriogenology 2010;73:577-86.
  • 21. Gonzalez VM, Fuertes MA, Alonso C, Perez JM. Is cisplatin-induced cell death always produced by apoptosis? Mol Pharmacol 2001;59:657-63.
  • 22. Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxi- dative stress and toxicity. J Toxicol 2012;2012:645460.
  • 23. Marcon L, Zhang X, Hales BF, Robaire B, Nagano MC. Effects of chemotherapeutic agents for testicular cancer on rat spermato- gonial stem/progenitor cells. J Androl 2011;32:432-43.
  • 24. Topcu-Tarladacalisir Y, Kanter M, Uzal MC. Role of L-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study. Arch Toxicol 2009;83:735-46.
  • 25. Ward MA. Intracytoplasmic sperm injection effects in infertile azh mutant mice. Biol Reprod 2005;73:193-200.
  • 26. Favareto AP, Fernandez CD, da Silva DA, Anselmo-Franci JA, Kempinas Wde G. Persistent impairment of testicular histology and sperm motility in adult rats treated with cisplatin at peri-puberty. Basic Clin Pharmacol Toxicol 2011;109:85-96.
  • 27. Ateşşahin A, Sahna E, Türk G, Ceribaşi AO, Yilmaz S, Yüce A, et al. Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res 2006;41:21-7.
  • 28. Lirdi LC, Stumpp T, Sasso-Cerri E, Miraglia SM. Amifostin protective effect on cisplatin-treated rat testis. Anat Rec (Hoboken) 2008;291:797-808.
Balkan Medical Journal-Cover
  • ISSN: 2146-3123
  • Başlangıç: 2015
  • Yayıncı: Erkan Mor
Sayıdaki Diğer Makaleler

Enhanced adhesion and OspC protein synthesis of the lyme disease spirochete Borrelia burgdorferi cultivated in a host- derived tissue co-culture system

Ece ŞEN, Leonard H. SIGAL

Advanced analysis of finger-tapping performance: A preliminary study

Ethem GELİR, Erhan KIZILTAN, Fürüzan KÖKTÜRK, Çağatay BARUT

Clinical features and prognostic factors of Hodgkin’s lymphoma: A single center experience

Uğur SELEK, İsmail ÇELİK, Ferah YILDIZ, Ayşe KARS, İbrahim BARIŞTA, Şükran ÜLGER, Gülten TEKUZMAN, Yavuz ÖZIŞIK, Saadettin KILIÇKAP

Orbital complications of sinusitis

Dritan VASILI, Pjerin RADOVANI, Mirela XHELILI, Julian DERVISHI

Detection of OXA-48-like carbapenemase-producing Klebsiella pneumoniae in a Tertiary Care Center in Turkey: Molecular characterization and epidemiology

Barış OTLU, Yusuf YAKUPOĞULLARI, Özlem AZAP, Ayşegül YEŞİLKAYA

Evaluation of visual evoked potentials in patient with angelmans syndrome - Case report

Tatjana KNEZEVİC, Ivana PETRONİC, Dejan NİKOLİC, Dragana CİROVİC, Vera KRSTİC, Sinisa DUCİC, Calogero FOTİ, Ljubica KONSTANTİNOVİC

Vocal fold hyperplastic lesions: An evaluation of surgical outcome with videolaryngostroboscopy

Ertuğrul ÇOLAK, Armağan İNCESULU, Melek Kezban GÜRBÜZ, Leman BİRDANE, Erkan ÖZÜDOĞRU, Cemal CİNGİ, Mustafa Fuat AÇIKALIN

Pityriasis rosea associated with pegylated interferon alfa and ribavirin treatment in a patient with chronic hepatitis C

İmran HASANOĞLU, Şiran KESKE, Mehmet TAŞYARAN, Rahmet GÜNER

Balanced chromosomal translocation of chromosomes 6 and 7: A rare male factor of spontaneous abortions

Ateş KADIOĞLU, Sefa RESİM, Erkan EFE, Tolga AKMAN, Ayşe Gül BAYRAK

Sequential test selection by quantifying of the reduction in diagnostic uncertainty for the diagnosis of proximal caries

Nursel AKKAYA, Ahmet Ergun KARAAĞAOĞLU, Umut ARSLAN, Hilmi KANSU, Leyla Berna ÇAĞIRANKAYA, Ayşe KANSU ÖZDEN