The effects of safranal against bisphenol AF on some reproductive parameters in male new zealand rabbits

Öz

Bisphenol AF (BPAF) is used as an analog of the endocrine disruptor Bisphenol A (BPA), whereas safranal is a powerful antioxidant obtained from the saffron plant. In the current study, the possible effects of BPAF and Safranal on some spermatological parameters, reproductive hormones, oxidant/antioxidant enzymes, and histopathological parameters were investigated. A total of 24 male New Zealand rabbits were divided into 4 groups (n= 6 for each group). The groups and the treatments they received by oral gavage for 9 weeks are as follows: The control group received by oral gavage 1 ml/day of corn oil, the BPAF group received by oral gavage 20 mg/kg/day of bisphenol AF, the Safranal group received by oral gavage 100 mg/kg/day safranal, and the treatment group received by oral gavage 20 mg/kg/day bisphenol AF and 100 mg/kg/day safranal. Although the spermatological parameters (sperm concentration, ejaculate volume, progressive motility, ejaculate weight, seminal plasma total protein, and pH) prior to the experiment revealed no differences among the groups, BPAF treatment reduced sperm quantity and motility at the end of the study. BPAF treatments also had a negative impact on testicular MDA and GSH levels. It also caused seminiferous tubule degeneration in testicular tissue. On the other hand, the administration of safranal with BPAF decreased estrogen levels while increasing sperm concentration and motility to control group levels. Thus, the results suggested that safranal could have a beneficial effect in reducing BPAF-induced tissue damage. In conclusion, BPAF may have potentially harmful to the male reproductive system and safranal may exhibit a protective effect against BPAF exposure.

Anahtar Kelimeler

• Bisphenol AF
• male
• rabbit
• reproduction
• safranal

Kaynakça

1. Aebi, H. (1984). “[13] Catalase in vitro”, Methods in enzymology, 105, 121-126.
2. Alayunt, Ö.N., Lacine, A., Karafakıoğlu, Y.S., Sevimli, S. (2019). 'Assessment of Anti-inflammatory and Antioxidant Properties of Safranal on CCI4-Induced Oxidative Stress and Inflammation in Rats', Anais da Academia Brasileira de Ciências, 91.
3. Asadi, M.H., Fariba, Z., Arash, S., Mehdi, A., Majid, S., Morteza, K., Abazar, Y., Rafieh, A.M. 2014. 'Saffron improves epididymal sperm parameters in rats exposed to cadmium', Nephro-urology monthly, 6.
4. Ata, A., Yildiz-Gulay, O., Güngör, S., Balic, A., & Gulay, M. S. (2018). The effect of carob (Ceratonia siliqua) bean extract on male New Zealand White rabbit semen. World Rabbit Science, 26(3), 209-215.
5. Ataei, G., & Rahbarian, R. (2020). Investigating the effect of safranal on Bax and Bcl2 and oxidative stress levels in testis tissue of streptozotocin-induced diabetic rats. KAUMS Journal (FEYZ), 24(1), 10-20.
6. Ataei, G., Raheleh, R. 2020. 'Investigating the effect of safranal on Bax and Bcl2 and oxidative stress levels in testis tissue of streptozotocin-induced diabetic rats', KAUMS Journal (FEYZ), 24: 10-20.
7. Aydoğan, M., Korkmaz, A., Barlas, N., & Kolankaya, D. (2010). Pro-oxidant effect of vitamin C coadministration with bisphenol A, nonylphenol, and octylphenol on the reproductive tract of male rats. Drug and Chemical Toxicology, 33(2), 193-203.
8. Beutler, E. 1963. 'Improved method for the determination of blood glutathione', J. lab. clin. Med., 61: 882-88.

9. Beutler, E. 1975. 'Glutathione in red blood cell metabolism', A manual of biochemical methods: 112-14.
10. Cai, M., Li, Y. Y., Zhu, M., Li, J. B., & Qin, Z. F. (2020). Evaluation of the effects of low concentrations of bisphenol AF on gonadal development using the Xenopus laevis model: A finding of testicular differentiation inhibition coupled with feminization. Environmental Pollution, 260, 113980.
11. Feng, Y., Yin, J., Jiao, Z., Shi, J., Li, M., & Shao, B. (2012). Bisphenol AF may cause testosterone reduction by directly affecting testis function in adult male rats. Toxicology letters, 211(2), 201-209.
12. Fic, A., Mlakar, S. J., Juvan, P., Mlakar, V., Marc, J., Dolenc, M. S., Brober, K., & Mašič, L. P. (2015). Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicology in Vitro, 29(5), 1060-1069.
13. Gao, Z., Liu, S., Tan, L., Gao, X., Fan, W., Ding, C., Li, M., Tang, Z., Shi, X., Luo, Y., & Song, S. (2022). Testicular toxicity of bisphenol compounds: Homeostasis disruption of cholesterol/testosterone via PPARα activation. Science of The Total Environment, 836, 155628.
14. Gu, J., Wang, H., Zhou, L., Fan, D., Shi, L., Ji, G., & Gu, A. (2020). Oxidative stress in bisphenol AF-induced cardiotoxicity in zebrafish and the protective role of N-acetyl N-cysteine. Science of the Total Environment, 731, 139190.
15. Gules, O., Yildiz, M., Naseer, Z., & Tatar, M. (2019). Effects of folic acid on testicular toxicity induced by bisphenol-A in male Wistar rats. Biotechnic & Histochemistry, 94(1), 26-35.
16. Herath, C. B., Jin, W., Watanabe, G., Arai, K., Suzuki, A. K., & Taya, K. (2004). Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats. Endocrine, 25(2), 163-172.
17. Heydarı, M., Rezanezhadı, J.B., Bahram, D., Mehdi, B., Hossein, K., Soudabeh, G. 2008. 'Effect of saffron on semen parameters of infertile men'.
18. Hosseinzadeh, H., Gholarnreza, K., Maryam, N. 2003. "Antidepressant effect of Crocus sativus L. stigma extracts and their constituents, crocin and safranal, in mice." In I International Symposium on Saffron Biology and Biotechnology, 650, 435-45.
19. Hosseinzadeh, H., Hamid, R.S. 2005. 'Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus', J Pharm Pharm Sci, 8: 394-99.
20. Hosseinzadeh, H., Modaghegh, M. H., & Saffari, Z. (2009). Crocus sativus L.(Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evidence-Based Complementary and Alternative Medicine, 6(3), 343-350.
21. Huang, M., Liu, S., Fu, L., Jiang, X., & Yang, M. (2020). Bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF induce oxidative stress and biomacromolecular damage in human granulosa KGN cells. Chemosphere, 253, 126707.
22. Jagne, J., White, D., & Jefferson, F. (2016). Endocrine-disrupting chemicals: adverse effects of bisphenol A and parabens to women’s health. Water, Air, & Soil Pollution, 227(6), 1-10.
23. Karabulut, H., & Gulay, M. S. (2022). Investigation of BPA Toxicity in Male New Zealand White Rabbits. European Journal of Veterinary Medicine, 2(2), 6-12.
24. Khayyat, S., Eman, E. 2018. 'Safranal epoxide–A potential source for diverse therapeutic applications', Saudi pharmaceutical journal, 26: 115-19.
25. Kianbakht, S, Hajiaghaee, R. 2011. 'Anti-hyperglycemic effects of saffron and its active constituents, crocin and safranal, in alloxan-induced diabetic rats', Journal of Medicinal Plants, 3: 82-89.
26. Li, J., Nan, S., Ruina, C., Yixing, F., Bing, S., Xuejiang, G., Hongxia, Z., Jiayin, D. 2016. 'Gestational and lactational exposure to bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring', Chemosphere, 163: 552-61.
27. Lowry, O.H., Nira, J.R., Lewis, F., Rose, J.R. 1951. 'Protein measurement with the Folin phenol reagent', Journal of biological chemistry, 193: 265-75.
28. Luna LG (1968). Manuel of Histologic Staining Methods of the Armed Forces Institute of Pathology. McGraw-Hill Book Co. Newyork, p- 32. Ma, Y., Liu, H., Wu, J., Yuan, L., Wang, Y., Du, X., Wang, R., Marwa, P.W, Petlulu, P., Chen, X., & Zhang, H. (2019). The adverse health effects of bisphenol A and related toxicity mechanisms. Environmental research, 176, 108575.
29. Maleki, B.H., Bakhtyar, T., Frank, C.M., Fakhreddin, Y.N., Mehdi, Y. 2016. 'Saffron supplementation ameliorates oxidative damage to sperm DNA following a 16-week low-to-intensive cycling training in male road cyclists', Journal of Functional Foods, 21: 153-66. Mardani, M., Ahmad, V., Shahnaz, R. 2014. 'Effect of saffron on rat sperm chromatin integrity', Iranian journal of reproductive medicine, 12: 343.
30. Meng, Z., Tian, S., Yan, J., Jia, M., Yan, S., Li, R., ... & Zhou, Z. (2019). Effects of perinatal exposure to BPA, BPF and BPAF on liver function in male mouse offspring involving in oxidative damage and metabolic disorder. Environmental pollution, 247, 935-943.
31. Mentor, A., Wänn, M., Brunström, B., Jönsson, M., & Mattsson, A. (2020). Bisphenol AF and bisphenol F induce similar feminizing effects in chicken embryo testis as bisphenol A. Toxicological Sciences, 178(2), 239-250.
32. Moreman, J., Lee, O., Trznadel, M., David, A., Kudoh, T., & Tyler, C. R. (2017). Acute toxicity, teratogenic, and estrogenic effects of bisphenol A and its alternative replacements bisphenol S, bisphenol F, and bisphenol AF in zebrafish embryo-larvae. Environmental science & technology, 51(21), 12796-12805.
33. National Institute of Health, National Library of Medicine, National Center for Biotechnology Information, (2022). https://pubchem.ncbi.nlm.nih.gov/compound/70699969 Date of Access: 16.06.2022.
34. Ohkawa, H., Nobuko, O., Kunio, Y. 1979. 'Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction', Analytical biochemistry, 95: 351-58.
35. Pandey, K. B., & Rizvi, S. I. (2010). Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxidative medicine and cellular longevity, 3(1), 2-12.
36. Rahaiee, S., Moini, S., Hashemi, M., & Shojaosadati, S. A. (2015). Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review. Journal of Food Science and Technology, 52(4), 1881-1888.
37. Rehfeld, A., Andersson, A. M., & Skakkebæk, N. E. (2020). Bisphenol A diglycidyl ether (BADGE) and bisphenol analogs, but not bisphenol A (BPA), activate the CatSper Ca2+ channel in human sperm. Frontiers in Endocrinology, 11, 324.
38. Riaz, A., Pasha, I., Sharif, M. K., & Javaria, S. (2021). Bisphenol A and its Analogues: Human Exposure and Biological Effects-A Review. Pakistan Journal of Scientific & Industrial Research Series A: Physical Sciences, 64(2), 173-190.
39. Sadeghnia, H.R., Hamideh, S., Fatemeh, F., Hossein, H. 2017. 'Neuroprotective effect of safranal, an active ingredient of Crocus sativus, in a rat model of transient cerebral ischemia', Folia Neuropathol, 55: 206-13.
40. Samarghandian, S., Azimi-Nezhad, M., & Samini, F. (2015). Preventive effect of safranal against oxidative damage in aged male rat brain. Experimental Animals, 64(1), 65-71.
41. Sarangarajan, R., Meera, S., Rukkumani, R., Sankar, P., & Anuradha, G. (2017). Antioxidants: Friend or foe?. Asian Pacific Journal of Tropical Medicine, 10(12), 1111-1116.
42. Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., ... & Conrad, M. (2009). Mitochondrial glutathione peroxidase 4 disruption causes male infertility. The FASEB journal, 23(9), 3233-3242.
43. Shi, J., Zhihao, J., Sai, Z., Ming, Li., Jing, Z., Yixing, F., Jie, Y., Bing, S. 2015. 'Long-term effects of bisphenol AF (BİSFENOL AF) on hormonal balance and genes of hypothalamus-pituitary-gonad axis and liver of zebra (Danio rerio), and the impact on offspring', Chemosphere, 128: 252-57.
44. Siracusa, J.S., Lei, Y., Emily, M., Shenuxan, L., Xiaozhong, Y. 2018. 'Effects of bisphenol A and its analogs on reproductive health: A mini review', Reproductive toxicology, 79: 96-123.
45. Song, M., Liang, D., Liang, Y., Chen, M., Wang, F., Wang, H., & Jiang, G. (2014). Assessing developmental toxicity and estrogenic activity of halogenated bisphenol A on zebrafish (Danio rerio). Chemosphere, 112, 275-281.
46. Sutherland, V. L., Johnson, C. L., McIntyre, B., Cunny, H., Turner, K., Foster, P. M., & Elmore, S. A. (2019). Reproductive and pathology assessment of bisphenol AF. Reproductive Toxicology, 88, 19-20.
47. Tian, F., Li, Q., Shi, L., Li, J., Shi, M., Zhu, Y., ... & Ge, R. S. (2022). In utero bisphenol AF exposure causes fetal Leydig cell dysfunction and induces multinucleated gonocytes by generating oxidative stress and reducing the SIRT1/PGC1α signals. Toxicology and Applied Pharmacology, 116069.
48. Ullah, A., Pirzada, M., Jahan, S., Ullah, H., & Khan, M. J. (2019). Bisphenol A analogues bisphenol B, bisphenol F, and bisphenol S induce oxidative stress, disrupt daily sperm production, and damage DNA in rat spermatozoa: A comparative in vitro and in vivo study. Toxicology and Industrial Health, 35(4), 294-303.
49. United States Environmental Protection Agency (EPA), (22 April, 2010). Toxicological Priority Index (ToxPi) as a Platform for Incorporation of Exposure Data for Chemical Prioritization. https://www.epa.gov/chemical-research/toxicological-priority-index-platform-incorporation-exposure-data-chemical
50. Vaez, A., Mohammad, M., Shahnaz, R. 2014. 'Impact of saffron on rat sperm membrane integrity and spermatogenesis status', Advanced biomedical research, 3.
51. Wang, H. F., Liu, M., Li, N., Luo, T., Zheng, L. P., & Zeng, X. H. (2016). Bisphenol a impairs mature sperm functions by a CatSper-relevant mechanism. Toxicological Sciences, 152(1), 145-154.
52. Wu, Di., Chun-Jie, H., Xiao-Fei, J., Zhi-Ming, D., Shou-Xin, Z., Yi-Liang, M., Li-Jun, H. 2019. 'Bisphenol AF compromises blood-testis barrier integrity and sperm quality in mice', Chemosphere, 237: 124410.
53. Xiao, X., Mruk, D. D., Wong, C. K., & Yan Cheng, C. (2014). Germ cell transport across the seminiferous epithelium during spermatogenesis. Physiology, 29(4), 286-298.
54. Yang, X., Yuchen, L., Jia, L., Minjie, C., Di, P., Yong, L., Maoyong, S., Jie, Z., Guibin, J. 2016. 'Exposure to Bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebra', Environmental toxicology, 31: 285-94.
55. Ye, L., Su, Z. J., & Ge, R. S. (2011). Inhibitors of testosterone biosynthetic and metabolic activation enzymes. Molecules, 16(12), 9983-10001. Yu, Y., Xin, X., Ma, F., Li, X., Wang, Y., Zhu, Q., Chen, H., Li, H., & Ge, R. S. (2022). Bisphenol AF blocks Leydig cell regeneration from stem cells in male rats. Environmental Pollution, 298, 118825.
56. Yusoff, N. A., Budin, S. B., & Taib, I. S. (2017). Pesticide exposures induce male-mediated reproductive toxicity: A review. J. Agric. Sci, 9, 122-135.
57. Zhang, Y., Yong, Z., Jianyou, G., Haifeng, C., Sha, L. 2018. 'Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway', Journal of BU ON.: official journal of the Balkan Union of Oncology, 23: 574.