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Potential anti-toxic effect of d-ribose-l-cysteine supplement on the reproductive functions of male rats administered cyclophosphamide

  • Gabriel O. Oludare EMAIL logo , Gbenga O. Afolayan and Ganbotei G. Semidara
Published/Copyright: February 9, 2021

Abstract

Objectives

This study aimed to access the protective effects of d-ribose-l-cysteine (DRLC) on cyclophosphamide (CPA) induced gonadal toxicity in male rats.

Methods

Forty-eight male Sprague-Dawley rats were divided into six groups of eight rats each. Group I the control, received distilled water (10 ml/kg), Group II received a single dose of CPA 100 mg/kg body weight intraperitoneally (i.p), Groups III and IV received a single dose of CPA at 100 mg/kg (i.p) and then were treated with DRLC at 200 mg/kg bodyweight (b.w) and 400 mg/kg b.w for 10 days, respectively. Rats in Groups V and VI received DRLC at 200 and 400 mg/kg b.w for 10 days, respectively. DRLC was administered orally.

Results

Results showed that CPA increased percentage of abnormal sperm cells and reduced body weight, sperm count, sperm motility, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels (p<0.05). CPA also induced oxidative stress as indicated by the increased malondialdehyde (MDA) content and reduced activities of the oxidative enzymes measured (p<0.05). Liver enzymes were elevated while the blood cells production was decreased in the rats administered CPA. DRLC supplementation enhanced the antioxidant defence system as indicated in the reduced MDA levels and increased activities of the antioxidant enzymes when compared with CPA (p<0.05). Bodyweight, sperm count, sperm motility, FSH, and testosterone levels were increased in the CPA + DRLC II group compared with CPA (p<0.05).

Conclusions

The results of this present study showed that DRLC has a potential protective effect on CPA-induced gonadotoxicity.


Corresponding author: Gabriel O. Oludare, Department of Physiology, College of Medicine of the University of Lagos, Lagos, Nigeria, Phone: +234 7035363115, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Research involving animals complied with all relevant national regulations and institutional policies for the care and use of animals.

References

1. Venkatesan, N, Chandrakasan, G. In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury. Eur J Pharmacol Environ Toxicol Pharmacol. 1994;292:75–80. https://doi.org/10.1016/0926-6917(94)90028-0.Search in Google Scholar

2. Kanno, TYN, Sensiate, LA, Paula, NAD, Salles, MJS. Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice. Braz J Pharmaceut Sci. 2009;45:313–9. https://doi.org/10.1590/s1984-82502009000200017.Search in Google Scholar

3. Hall, AG, Tilby, MJ. Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies. Blood Rev. 1992;6:163–73. https://doi.org/10.1016/0268-960x(92)90028-o.Search in Google Scholar

4. Allison, AC. Immunosuppressive drugs: the first 50 years and a glance forward. Immunopharmacology. 2000; 47:63–83. https://doi.org/10.1016/s0162-3109(00)00186-7.Search in Google Scholar

5. Medubi, L, Ama, C, Medubi, O, Onwosu, NC, Lawal, O, Osinubi, A. D-Ribose-L-cysteine-rich supplement attenuates doxorubicin-induced impaired spermatogenesis, testicular steroidogenesis and redox status in Sprague-Dawley rats. Afr J Biomed Res. 2019;22:179–85.Search in Google Scholar

6. Kenney, LB, Laufer, MR, Grant, FD, Grier, H, Diller, L. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer. 2001;91:613–21.10.1002/1097-0142(20010201)91:3<613::AID-CNCR1042>3.0.CO;2-RSearch in Google Scholar

7. Traila, A, Dima, D, Achimas-Cadariu, P, Micu, R. Fertility preservation in Hodgkin’s lymphoma patients that undergo targeted molecular therapies: an important step forward from the chemotherapy era. Canc Manag Res. 2018; 10:1517–26. https://doi.org/10.2147/cmar.s154819.Search in Google Scholar

8. Bieber, AM. Effects of chemotherapeutic agents for testicular cancer on the male rat reproductive system, spermatozoa, and fertility. J Androl. 2006; 27:189–200. https://doi.org/10.2164/jandrol.05103.Search in Google Scholar

9. Pectasides, D, Pectasides, M, Farmakis, D, Nikolaou, M, Koumpou, M, Kostopoulou, V, et al.. Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC90) combination chemotherapy. Eur Urol. 2004; 45:187–93. https://doi.org/10.1016/j.eururo.2003.09.010.Search in Google Scholar

10. Williams, DH. Sperm banking and the cancer patient. Ther Adv Urol. 2010; 2:19–34. https://doi.org/10.1177/1756287210368279.Search in Google Scholar

11. Singh, K, Bhori, M, Kasu, YA, Bhat, G, Marar, T. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity – exploring the armoury of obscurity. Saudi Pharmaceut J. 2018; 26:177–90. https://doi.org/10.1016/j.jsps.2017.12.013.Search in Google Scholar

12. Stankiewicz, A, Skrzydlewska, E, Makiela, M. Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats. Drug Metabol Drug Interact. 2002;19. https://doi.org/10.1515/dmdi.2002.19.2.67.Search in Google Scholar

13. Shanmugarajan, TS, Arunsundar, M, Somasundaram, I, Sivaraman, D, Krishnakumar, E, Ravichandran, V. Ameliorative effect of Ficus hispida Linn. leaf extract on cyclophosphamide-induced oxidative hepatic injury in rats. J Pharmacol Toxicol. 2008;3:363–72. https://doi.org/10.3923/jpt.2008.363.372.Search in Google Scholar

14. Arumugam, N, Sivakumar, V, Thanislass, J, Devaraj, H. Effects of acrolein on rat liver antioxidant defense system. Indian J Exp Biol. 1997;35:1373–4.Search in Google Scholar

15. Sznarkowska, A, Kostecka, A, Meller, K, Bielawski, KP. Inhibition of cancer antioxidant defense by natural compounds. Oncotarget. 2016;8:15996–6016. https://doi.org/10.18632/oncotarget.13723.Search in Google Scholar

16. Pizzorno, J. Glutathione! integrative medicine: Clinician J. 2014;13:8.Search in Google Scholar

17. Carr, A, Cooper, DA, Penny, R. Allergic manifestations of human immunodeficiency virus (HIV) infection. J Clin Immunol. 1991;11:55–64. https://doi.org/10.1007/bf00917741.Search in Google Scholar

18. Meschino, JP. Glutathione: the body’s master detoxifier and antioxidant. Dyn Chiropr Can. 2010;3:1–11.Search in Google Scholar

19. Israel, N, Gougerot-Pocidalo, M, Aillet, F, Virelizier, J. Redox status of cells influences constitutive or induced NF-kappa B translocation and HIV long terminal repeat activity in human T and monocytic cell lines. J Immunol. 1992;149:3386–93.10.4049/jimmunol.149.10.3386Search in Google Scholar

20. Witschi, A, Reddy, S, Stofer, B, Lauterburg, BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43:667–9. https://doi.org/10.1007/bf02284971.Search in Google Scholar

21. Roberts, JC, Nagasawa, HT, Zera, RT, Fricke, RF, Goon, DJW. Prodrugs of L-cysteine as protective agents against acetaminophen-induced hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(polyacetoxyalkyl)thiazolidine-4(R)-carboxylic acids. J Med Chem. 1987; 30:1891–6. https://doi.org/10.1021/jm00393a034.Search in Google Scholar

22. Roberts, JC, Francetic, DJ, Zera, RT. L-Cysteine prodrug protects against cyclophosphamide urotoxicity without compromising therapeutic activity. Canc Chemother Pharmacol. 1991; 28:166–70. https://doi.org/10.1007/bf00685504.Search in Google Scholar

23. Melissa, R. Sperm morphology: in pathophysiology of the reproductive system, glossary of hypertexts for biomedical sciences. 2004 [cited 2020-18-May].Search in Google Scholar

24. Zemjanis, R. Collection and evaluation of semen. Diagnostic and therapeutic technique in animal reproduction. 1970;vol. 2:467–523.Search in Google Scholar

25. King, E. Calcium, phosphorus, and phosphatase. Pract Clin Biochem. 1988;458.Search in Google Scholar

26. Uchiyama, M, Mihara, M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86:271–8. https://doi.org/10.1016/0003-2697(78)90342-1.Search in Google Scholar

27. Sun, M, Zigman, S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem. 1978;90:81–9. https://doi.org/10.1016/0003-2697(78)90010-6.Search in Google Scholar

28. Aebi, H. Catalase in vitro. Methods Enzymol. Elsevier 1984;105:121–6.10.1016/S0076-6879(84)05016-3Search in Google Scholar

29. Gunzler, WA. Glutathione peroxidase. CRC handbook of methods for oxygen radical research. 1985:285–90.Search in Google Scholar

30. Agarwal, A, Mulgund, A, Hamada, A, Chyatte, MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13. https://doi.org/10.1186/s12958-015-0032-1.Search in Google Scholar

31. Lee, S, Schmitt, CA. Chemotherapy response and resistance. Curr Opin Genet Dev. 2003;13:90–6. https://doi.org/10.1016/s0959-437x(02)00014-x.Search in Google Scholar

32. Abarikwu, SO, Ekor, M, Osobu, D, Otuechere, CA, Monwuba, K. Rutin ameliorates cyclophosphamide-induced reproductive toxicity in male rats. Toxicol Int. 2012;19:207. https://doi.org/10.4103/0971-6580.97224.Search in Google Scholar

33. Zhao, H, Jin, B, Zhang, X, Cui, Y, Sun, D, Gao, C, et al.. Yangjing capsule ameliorates spermatogenesis in male mice exposed to cyclophosphamide. Evid Base Compl Alternative Med. 2015;2015:1–8. https://doi.org/10.1155/2015/980583.Search in Google Scholar

34. Howell, SJ, Shalet, SM. Testicular function following chemotherapy. Hum Reprod Update. 2001;7:363–9. https://doi.org/10.1093/humupd/7.4.363.Search in Google Scholar

35. Oduwole, OO, Peltoketo, H, Huhtaniemi, IT. Role of follicle-stimulating hormone in spermatogenesis. Front Endocrinol. 2018; 9. https://doi.org/10.3389/fendo.2018.00763.Search in Google Scholar

36. Anjum, S, Khan, S, Baig, S, Khanum, A, Haider, M, Qazi, M. Effect of chemotherapy on circulating steroid hormone levels in postoperative premenopausal breast cancer patients. J Pak Med Assoc. 1991;41:296–8.Search in Google Scholar

37. Al-Bader, M, Kilarkaje, N. Effects of bleomycin, etoposide and cisplatin treatment on Leydig cell structure and transcription of steroidogenic enzymes in rat testis. Eur J Pharmacol. 2015;747:150–9. https://doi.org/10.1016/j.ejphar.2014.12.006.Search in Google Scholar

38. Nelli, G, Pamanji, SR. Di-n-butyl phthalate prompts interruption of spermatogenesis, steroidogenesis, and fertility associated with increased testicular oxidative stress in adult male rats. Environ Sci Pollut Control Ser. 2017;24:18563–74. https://doi.org/10.1007/s11356-017-9478-3.Search in Google Scholar

39. Prathima, P, Venkaiah, K, Pavani, R, Daveedu, T, Munikumar, M, Gobinath, M, et al.. α-Lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period. Toxicol Rep. 2017;4:373–81. https://doi.org/10.1016/j.toxrep.2017.06.009.Search in Google Scholar

40. Gaschler, MM, Stockwell, BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 2017;482:419–25. https://doi.org/10.1016/j.bbrc.2016.10.086.Search in Google Scholar

41. Groopman, JE, Itri, LM. Chemotherapy-induced anemia in adults: incidence and treatment. JNCI J Natl Canc Inst. 1999;91:1616–34. https://doi.org/10.1093/jnci/91.19.1616.Search in Google Scholar

42. Huang, J-q, Pang, M-r, Li, G-y, Wang, N, Jin, L, Zhang, Y. Alleviation of cyclophosphamide-induced immunosuppression in mice by naturally acetylated hemicellulose from bamboo shavings. Food Agric Immunol. 2017;28:328–42. https://doi.org/10.1080/09540105.2016.1272553.Search in Google Scholar

43. Diotallevi, M, Checconi, P, Palamara, AT, Celestino, I, Coppo, L, Holmgren, A, et al.. Glutathione fine-tunes the innate immune response toward antiviral pathways in a macrophage cell line independently of its antioxidant properties. Front Immunol. 2017;8. https://doi.org/10.3389/fimmu.2017.01239.Search in Google Scholar

44. Oyagbemi, A, Omobowale, O, Asenuga, E, Akinleye, A, Ogunsanwo, R, Saba, A. Cyclophosphamide-induced hepatotoxicity in wistar rats: the modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical. Int J Prev Med. 2016;7:51. https://doi.org/10.4103/2008-7802.177898.Search in Google Scholar

45. Temel, Y, Kucukler, S, Yıldırım, S, Caglayan, C, Kandemir, FM. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. N Schmied Arch Pharmacol. 2019;393:325–37. https://doi.org/10.1007/s00210-019-01741-z.Search in Google Scholar

46. Dentico, P, Volpe, A, Buongiorno, R, Grattagliano, I, Altomare, E, Tantimonaco, G, et al.. Glutathione in the treatment of chronic fatty liver diseases. Recent Prog Med. 1995;86:290–3.Search in Google Scholar

47. Honda, Y, Kessoku, T, Sumida, Y, Kobayashi, T, Kato, T, Ogawa, Y, et al.. Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study. BMC Gastroenterol. 2017;17. https://doi.org/10.1186/s12876-017-0652-3.Search in Google Scholar

48. Ray, S, Pandit, B, Das, S, Chakraborty, S. Cyclophosphamide-induced lipid peroxidation and changes in cholesterol content: protective role of reduced glutathione. Iran J Pharm Sci. 2011;7: 255–67.Search in Google Scholar

Received: 2020-09-11
Accepted: 2020-12-22
Published Online: 2021-02-09

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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