Yıl: 2023 Cilt: 53 Sayı: 1 Sayfa Aralığı: 40 - 50 Metin Dili: İngilizce DOI: 10.55730/1300-0144.5556 İndeks Tarihi: 23-03-2023

The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats

Öz:
Background/aim: Paclitaxel is a widely used drug for the treatment of cancer, but it possesses toxic effects on male reproductive system. Administering paclitaxel with an antioxidant has become a strategy for preventing the side effects of paclitaxel. Although curcumin is an antioxidant, data concerning the effect of curcumin on paclitaxel-induced testis tissue are lacking. The present study was established to examine the protective impact of curcumin against testicular damage induced by paclitaxel. Materials and methods: In the study, 40 Wistar albino male rats were used and randomly divided into 4 groups (n:10). The control group received only saline solution; the curcumin group received curcumin throughout the experiment; the paclitaxel group received a total of four doses of paclitaxel on days 1, 7, 14, and 21 of the experiment; curcumin + paclitaxel group received curcumin throughout the experiment and a total of four doses of paclitaxel on days 1, 7, 14, and 21 of the experiment. At the end of the experiment, the rats were decapitated under xylazine and ketamine anesthesia and their testicles were removed. The sections obtained from the testicles were stained with Hematoxylin & Eosin and histopathological damage was evaluated. The TUNEL method was applied to determine apoptotic cells. Testosterone levels were measured in the blood serum. The Johnsen testicular biopsy score (JTBS) was used to evaluate testicular tubules. DNA damage was evaluated in sperm samples taken from the ductus epididymis using the comet assay technique. Results: Testicular tissue was severely damaged in the paclitaxel group. In the curcumin + paclitaxel group, it was determined that the administration of curcumin with paclitaxel reduced the histological damage in the testicular tissue. Moreover, according to the JTBS, the value was significantly higher in the testicular tubules (p < 0.05). Testosterone levels were higher in curcumin + paclitaxel group than in paclitaxel group. DNA damage also decreased significantly in curcumin + paclitaxel group when compared to paclitaxel group (p < 0.05). Conclusion: The results showed that curcumin may be protective against damage caused by paclitaxel in the testicles of rats.
Anahtar Kelime: Paclitaxel curcumin comet assay rat testes

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  • 1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA-A Cancer Journal for Clinicians 2015; 65 (1): 5-29. https://doi. org/10.3322/caac.21254
  • 2. Holohan C, Schaeybroeck SV, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nature Reveviews Cancer 2013; 13 (10): 714-726. https://doi: 10.1038/ nrc3599
  • 3. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M et al. Drug resistance in cancer: an overview. Cancers 2014; 6 (3):1769-1792. https://doi: 10.3390/cancers6031769
  • 4. Sabanegh ESJr, Ragheb AM. Male fertility after cancer. Urology 2009; 73 (2): 225-231. https://doi.org/10.1016/j. urology.2008.08.474
  • 5. Meistirch ML. Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertility and Sterility 2013; 100 (5):1180-1186. https://doi: 10.1016/j.fertnstert.2013.08.010
  • 6. Rivkees SA, Crawford JD. The relationship of gonaldal activity and chemotherapy-induced gonadal damage. JAMA 1988; 259 (14): 2123-2125.
  • 7. Williams DH. Sperm banking and the cancer patient. Advances Urology. 2010; 2 (1): 19-34. https://doi: 10.1177/1756287210368279
  • 8. Barbuti AM, Chen ZS. Paclitaxel through the ages of anticancer therapy: exploring its role in chemoresistance and radiation therapy. Cancers 2015; 7 (4): 2360-2371. https://doi. org/10.3390/cancers7040897
  • 9. Okano J, Rustgi AK. Paclitaxel induces prolonged activation of the RAS/Mek/ERK pathway independently of activating the programmed cell death machinery. Journal of Biological Chemistry 2001; 276 (22): 19555-19564. https://doi: 10.1074/ jbc.M011164200
  • 10. Fu Y, Li S, Zu Y, Yang G, Yang Z et al. Medicinal cehmistry of paclitaxel and its analogues. Current Medicinal Chemistry 2009; 16 (30): 3966-3985. https://doi. org/10.2174/092986709789352277
  • 11. Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C et al. A polymer based, paclitaxel-elutingstent in patients with coronary artery disease. New England Journal of Medicine 2004; 350 (3): 221-231. https://doi.org/10.1056/NEJMoa032441
  • 12. Varbiro G, Veres B, Gallyas FJr. Sumegi B. Direct effect of Taxol on free radical formation and mitochondrial permeability transition. Free Radical Biology and Medicine 2001; 31 (4): 548-558. https://doi.org/10.1016/S0891-5849[01]00616-5
  • 13. Li B, He X, Zhuang M, Niu B, Wu C et al. Melatonin ameliorates busulfan-induced spermatogonial stem cell oxidative apoptosis in mouse testes. Antioxidant&Redox Signaling 2018; 28(5): 385-400. https://doi: 10.1089/ars.2016.6792
  • 14. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 277: 665-667.
  • 15. Mehdawi NAR. Curcumin Based Diazoles and Oxazoles with Potential Antibacterial Activities, AnNajah National University Faculty of Graduate Studies, Palestine, 2010.
  • 16. Ilbey YO, Ozbek E, Cekmen M, Simsek A, Otunctemur A et al. Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Human Reproduction 2009; 24 (7): 1717-1725. https://doi: 10.1093/humrep/dep058
  • 17. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F et al. Chemopreventive and therapeutic effects of curcumin. Cancer Letters 2005; 223(2) :181-190. https://doi: 10.1016/j. canlet.2004.09.041
  • 18. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR et al. Design of curcumin loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and supreior biovailability in vivo. Biochemical Pharmacology 2009; 79 (3): 330-338. https://doi: 10.1016/j.bcp.2009.09.003
  • 19. Nair KL, Thulasiodasan AKT, Deepa G, Anto RJ, Kumar GSV. Purely aqueous PLGA nanoparticulate formulations of curcumin exhibit enhanced anticancer activity with dependence on the combination of the carrier. Intetnational Journal of Pharmaceutial Research and Allied Sciences 2012; 425 (1-2): 44-52. https://doi: 10.1016/j.ijpharm.2012.01.003
  • 20. Priyadarsini KI. The chemistry of curcumin: From extraction to therapeutic agent. Molecules 2014; 19 (12): 20091-20112. https://doi: 10.3390/molecules191220091
  • 21. Calaf GM, Echiburu-Chau C, Roy D, Chai Y, Wen G et al. Protective role of curcumin in oxidative stress of breast cells. Oncology Reports 2011; 26 (4): 1029-1035. https://doi: 10.3892/or.2011.1386
  • 22. Calaf GM, Echiburu-Chau C, Wen G, Balajee AS, Roy D. Effect of curcumin on irradiated and estrogen transformed human breast cell lines. International Journal of Oncology 2012; 40 (2): 436-442. https://doi: 10.3892/ijo.2011.1228
  • 23. Sharma RA, Gescher AJ, Steward WP. Curcumin: The story so far. European Journal of Cancer 2005; 41 (13): 1955-1968. https://doi.org/10.1016/j.ejca.2005.05.009
  • 24. Lin JK, Lin-Shiau SY. Mechanisms of cancer chemoprevention by curcumin, Proceeding of the Indian National Science Academy 2001; 25 (2): 59-66.
  • 25. Pari L, Tewas D, Eckel J. Role of curcumin in health and disease, Archives of Physiology And Biochemistry 2008; 114 (2): 127-149. https://doi.org/10.1080/13813450802033958
  • 26. Goel A, Kunnumakara AB ve Aggarwal BB. Curcumin as ‘Curecumin’: from kitchen to clinic. Biochemical Pharmacology 2008; 75 (4): 787-809. https://doi.org/10.1016/j. bcp.2007.08.016
  • 27. Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Annales Academiae Scientiarum Fennicae- Mathematica 2005; 1056: 206-217. https://doi: 10.1196/ annals.1352.010
  • 28. 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 (1): 2-25. https://doi: 10.1159/000178170
  • 29. Ili P, Sari F, Bucak MN, Öztürk C, Güngör Ş et al. DNA damaging effect of paclitaxel in the epididymal sperms as a chemotherapeutic agent and possible remedies to prevent this effect: A study on reproductive potential male patients of reproductive age, Theriogenology 2019; 132: 201-211. https:// doi: 10.1016/j.theriogenology.2019.04.015
  • 30. Salama AF, Al-Bahr SM. Effect of curcumin on cadmium- induced oxidative testicular damage in rats. Journal of Medical Research Institute 2007; 28 (2): 167-173.
  • 31. Sariözkan S, Türk G, Güvenç M, Yüce A, Özdamar S et al. Effects of cinnamon (C. Zeylanicum) bark oil against taxanes-induced damages in sperm quality, testicular and epididymal oxidant/ antioxidant balance, testicular apoptosis, and sperm DNA integrity. Nutrition and Cancer-An International Journal 2016; 68 (3): 481-494. https://doi: 10.1080/01635581.2016.1152384
  • 32. Demirci U, Benekli M, Buyukberber S, Coskun U. Late side effects of cancer therapy. International Journal of Hematology and Oncology 2010; 20 (4): 250-261.
  • 33. Ragheb AM, Sabanegh ES. Male fertility-implications of anticancer treatment and strategies to mitigate gonadotoxicity. Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (1): 92- 102. https://doi: 10.2174/1871520611009010092
  • 34. Schrader M, Müller M, Straub B, Miller K. The impact of chemotherapy on male fertility: a survey of the biologic, basis and clinical aspects. Reproductive Toxicology 2001; 15 (6): 611-617. https://doi.org/10.1016/S0890-6238[01]00182-4
  • 35. Meistrich ML. Male gonadal toxicity. Pediatric Blood & Cancer 2009; 53 (2): 261-266. https://doi.org/10.1002/pbc.22004
  • 36. Delbes G, Hales BF, Robaire B. Toxicants and human sperm chromatin integrity. Molecular Human Reproduction 2010; 16 (1): 14-22. https://doi: 10.1093/molehr/gap087
  • 37. Güven MC, Can B, Ergün A, Saran Y, Aydos K. Ultrastructural effects of cigarette smoke on rat testis. European Urology 1999; 3 (6): 645-649. https://doi.org/10.1159/000020061
  • 38. Colpi GM, Contalbi GF, Nerva F, Sagone P, Piediferro G. Testicular function following chemo-radiotherapy. European Journal of Obstetrics&Gynecology and Reproductive Biology 2004; 113 (1): 2-6. https://doi.org/10.1016/j.ejogrb.2003.11.002
  • 39. Koehler-Samouilidou G, Kaldrymidou E, Papaioannou N, Kotsaki-Kovatsi VP, Vadarakis A. The effect of paclitaxel (taxol) on the reproductive system and the semen parameters as well as on other organs of male rats. Journal of the Hellenic Veterinary Medical Society 2001; 52 (1): 23-31. https:// doi:10.12681/jhvms.15403
  • 40. Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxidative Medicine and Cellular Longevity 2008; 1 (1): 15-24. https://doi: 10.4161/oxim.1.1.6843
  • 41. Chatterjee R, Haines GA, Perera DM, Goldstone A, Morris ID. Testicular and sperm DNA damage after treatment with fludarabine for chronic lymphocytic leukaemia. Human Reproduction 2000; 15: 762-766. https://doi.org/10.1093/ humrep/15.4.762
  • 42. Chatzidarellis E, Makrilia N, Giza L, Georgiadis E, Alamara C et al. Effects of taxane-based chemotherapy on inhibin B and gonadotropins as biomarkers of spermatogenesis. Fertility And Sterility 2010; 94 (2): 558-563. https://doi: 10.1016/j. fertnstert.2009.03.068
  • 43. Nouri HS, Azarmi Y, Movahedin M. Effect of growth hormone on testicular dysfunction induced by methotrexate in rats. Andrologia 2009; 41 (2): 105-110.
  • 44. Padmanabhan S, Tripathi DN, Vikram A, Ramarao P, Jena GB. Cytotoxic and genotoxic effects of methotrexate in germ cells of male swiss mice. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 2008; 655 (1-2): 59-67. https://doi: 10.1016/j.mrgentox.2008.07.003
  • 45. Shrestha S, Dhungel S, Saxena AK, Bhattacharya S, Maskey D. Effect of methotrexate (MTX) administration on spermatogenesis: an experiment on animal model. Nepal Medical College Journal. 2007; 9 (4): 230-233.
  • 46. Saxena AK, Dhungel S, Bhattacharya S, Jha CB, Srivastava AK. Effect of chronic low dose of methotrexate on cellular proliferation during spermatogenesis in rats. Archivio Italiano Di Urologia E Andrologia 2004; 50: 33-35. https://doi. org/10.1080/01485010490250533
  • 47. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research 1988; 175 (1) : 184-191. https://doi: 10.1016/0014-4827(88)90265-0
  • 48. Klempner SJ, Bubley G. Complementary and alternative medicines in prostate cancer: from bench to bedside? Oncologist 2012; 17 (6): 830-837. https://doi: 10. 1634/ theoncologist.2012-0094
  • 49. Giannessi F, Giambelluca MA, Grasso L, Scavuzzo MC, Ruffoli R. Curcumin protects Leydig cells of mice from damage induced by chronic alcohol administration. Medical Science Monitor Basic Research 2008; 14 (11): 237-242.
  • 50. Sharma P, Singh R. Protective role of curcumin on lindane induced reproductive toxicity in male Wistar rats. Bulletin Of Environmental Contamination and Toxicology 2010; 84 (4): 378-384.
APA Balcıoğlu E, Göktepe Ö, CANTÜRK F, bilgici p, yakan b, özdamar s (2023). The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. , 40 - 50. 10.55730/1300-0144.5556
Chicago Balcıoğlu Esra,Göktepe Özge,CANTÜRK Fazile,bilgici pınar,yakan birkan,özdamar saim The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. (2023): 40 - 50. 10.55730/1300-0144.5556
MLA Balcıoğlu Esra,Göktepe Özge,CANTÜRK Fazile,bilgici pınar,yakan birkan,özdamar saim The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. , 2023, ss.40 - 50. 10.55730/1300-0144.5556
AMA Balcıoğlu E,Göktepe Ö,CANTÜRK F,bilgici p,yakan b,özdamar s The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. . 2023; 40 - 50. 10.55730/1300-0144.5556
Vancouver Balcıoğlu E,Göktepe Ö,CANTÜRK F,bilgici p,yakan b,özdamar s The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. . 2023; 40 - 50. 10.55730/1300-0144.5556
IEEE Balcıoğlu E,Göktepe Ö,CANTÜRK F,bilgici p,yakan b,özdamar s "The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats." , ss.40 - 50, 2023. 10.55730/1300-0144.5556
ISNAD Balcıoğlu, Esra vd. "The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats". (2023), 40-50. https://doi.org/10.55730/1300-0144.5556
APA Balcıoğlu E, Göktepe Ö, CANTÜRK F, bilgici p, yakan b, özdamar s (2023). The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. Turkish Journal of Medical Sciences, 53(1), 40 - 50. 10.55730/1300-0144.5556
Chicago Balcıoğlu Esra,Göktepe Özge,CANTÜRK Fazile,bilgici pınar,yakan birkan,özdamar saim The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. Turkish Journal of Medical Sciences 53, no.1 (2023): 40 - 50. 10.55730/1300-0144.5556
MLA Balcıoğlu Esra,Göktepe Özge,CANTÜRK Fazile,bilgici pınar,yakan birkan,özdamar saim The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. Turkish Journal of Medical Sciences, vol.53, no.1, 2023, ss.40 - 50. 10.55730/1300-0144.5556
AMA Balcıoğlu E,Göktepe Ö,CANTÜRK F,bilgici p,yakan b,özdamar s The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. Turkish Journal of Medical Sciences. 2023; 53(1): 40 - 50. 10.55730/1300-0144.5556
Vancouver Balcıoğlu E,Göktepe Ö,CANTÜRK F,bilgici p,yakan b,özdamar s The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats. Turkish Journal of Medical Sciences. 2023; 53(1): 40 - 50. 10.55730/1300-0144.5556
IEEE Balcıoğlu E,Göktepe Ö,CANTÜRK F,bilgici p,yakan b,özdamar s "The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats." Turkish Journal of Medical Sciences, 53, ss.40 - 50, 2023. 10.55730/1300-0144.5556
ISNAD Balcıoğlu, Esra vd. "The role of curcumin against paclitaxel-induced oxidative stress and DNA damage in testes of adult male rats". Turkish Journal of Medical Sciences 53/1 (2023), 40-50. https://doi.org/10.55730/1300-0144.5556