The effect of cyclophosphamide combined with zinc on male mice Mus musculus spermatozoa
Abstract
Background: The usage of cyclophosphamide leads to infertility of reproductive system caused by acrolein. Acrolein can itself cause oxidative damage by depletion of cellular glutathione (GSH) by conjugation, leading to membrane disruption, DNA and mitochondrial damage and can exacerbate apoptosis, which may affect spermatogenesis. Zinc (Zn) which is constituents of superoxide dismutase, has a protective effect towards free radicals from physiological or pathologic effects to minimize the cell’s damage.
Objective: The purpose of this research was to know the effect of Zn on the spermatozoa count of Mus musculus that was given cyclophosphamide intraperitoneally.
Methods: In the present study, cyclophosphamide was administered in saline 200 mg/kg 1x weekly for 5 weeks by ip route, whereas Zn was supplemented by oral route with doses of 25, 50, 100 mg/Kg/day for 5 weeks. The data were analyzed with Anova and followed by Bonferroni Test at a significant level of 5%.
Results: The result of this research revealed that high Zn diet and Cp administration decrease sperm count simultaneously. It showed by the decrease of sperm count from 1490 (1 x 103)/ml sperm in the control group becomes 240 (1 x 103)/ml sperm in treatment group with 100 mg/kg of oral Zn and 200 mg/kg of cyclophosphamide.
Conclusion: This research shows that Zn supplement to prevent cyclophosphamide toxic effect in spermatogenesis does not have a protective effect, in fact its reduce sperm count by excess of Methallothine production and alter the spermatogenesis by reduce Cu intake from intestine.
References
Maremanda KP, Khan S, Jena G. Zinc protects cyclophosphamide-induced testicular damage in rat: Involvement of metallothionein, tesmin and Nrf2. Biochem Biophys Res Commun. 2014;445(3):591-6. https://doi.org/10.1016/j.bbrc.2014.02.055
Luberda Z. The role of glutathione in mammalian gametes. Reprod Biol. 2005;5(1):5-17.
Guerriero G, Trocchia S, Abdel-Gawad FK, Ciarcia G. Roles of reactive oxygen species in the spermatogenesis regulation. Front Endocrinol (Lausanne). 2014;5(56):10-3. https://doi.org/10.3389/fendo.2014.00056
De Jonge ME. Clinical pharmacokinetics of cyclophosphamide. Vol. 44, Clinical Pharmacokinetics. 2005. https://doi.org/10.2165/00003088-200544110-00003
Moghe A, Ghare S, Lamoreau B, Mohammad M, Barve S, McClain C, et al. Molecular mechanisms of acrolein toxicity: Relevance to human disease. Toxicol Sci. 2015;143(2):242-55. https://doi.org/10.1093/toxsci/kfu233
Ruttkay-Nedecky B, Nejdl L, Gumulec J, Zitka O, Masarik M, Eckschlager T, et al. The role of metallothionein in oxidative stress. Int J Mol Sci. 2013;14(3):6044-66. https://doi.org/10.3390/ijms14036044
Chasapis CT, Spiliopoulou CA, Loutsidou AC, Stefanidou ME. The Antioxidant Properties of Zinc. Arch Toxicol. 2012;86(4):521-34. https://doi.org/10.1007/s00204-011-0775-1
Powell SR. The Antioxidant Properties of Zinc1. Am Soc Nutr Sci. 2000;130(5):1344S-1349S. https://doi.org/10.1093/jn/130.5.1344S
Kanno TYN, Sensiate LA, De Paula NA, Salles MJS. Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice. Brazilian J Pharm Sci. 2009;45(2):313-9. https://doi.org/10.1590/S1984-82502009000200017
Adler ID. Spermatogenesis and mutagenicity of environmental hazards: Extrapolation of genetic risk from mouse to man. Andrologia. 2000;32(4-5):233-7. https://doi.org/10.1046/j.1439-0272.2000.00390.x
Imade GE, Towobola OA, Sagay AS, Otubu JAM. Discrepancies in sperm count using improved Neubauer, Makler, and Horwells counting chambers. Syst Biol Reprod Med. 1993;31(1):17-22. https://doi.org/10.3109/01485019308988375
Payaran KO, Wantouw B, Tendean L. Pengaruh pemberian zink terhadap kualitas spermatozoa pada mencit jantan (Mus musculus). J e-Biomedik. 2014;2(2):496-500. https://doi.org/10.35790/ebm.2.2.2014.5044
Kerns K, Zigo M, Sutovsky P. Zinc: A necessary ion for mammalian sperm fertilization competency. Int J Mol Sci. 2018;19(12):1-18. https://doi.org/10.3390/ijms19124097
Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins WD, Levinson BS, et al. Zinc-induced copper deficiency: A report of three cases initially recognized on bone marrow examination. Am J Clin Pathol. 2005;123(1):125-31. https://doi.org/10.1309/V6GVYW2QTYD5C5PJ
Tvrda E, Peer R, Sikka SC, Agarwal A. Iron and copper in male reproduction: a double-edged sword. J Assist Reprod Genet. 2014;32(1):3-16. https://doi.org/10.1007/s10815-014-0344-7
Beaudoin J, Ioannoni R, Labbé S. Mfc1 is a novel copper transporter during meiosis. Commun Integr Biol. 2012;5(2):118-21. https://doi.org/10.4161/cib.18716

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