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Protective effects of saffron against zearalenone-induced alterations in reproductive hormones in female mice (Mus musculus)

  • Ahmad, Bashir (Laboratory of Endocrinology, Department of Bioscience, Barkatullah University) ;
  • Shrivastava, Vinoy K. (Laboratory of Endocrinology, Department of Bioscience, Barkatullah University) ;
  • Saleh, Ramadan (Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University) ;
  • Henkel, Ralf (Department of Medical Bioscience, University of the Western Cape) ;
  • Agarwal, Ashok (American Center for Reproductive Medicine, Urological Institute, Cleveland Clinic)
  • 투고 : 2018.05.06
  • 심사 : 2018.10.16
  • 발행 : 2018.12.31

초록

Objective: Zearalenone (ZEA) is a mycotoxin with potent estrogenic effects. Saffron is an herbal product that has antioxidant activities. The objective of this study was to investigate the protective role of saffron against reproductive toxicity induced by ZEA in female mice. Methods: Ninety 8-week-old female mice were randomly allocated into three treatment groups. The first group received an intraperitoneal injection of ZEA (2.5 mg/kg) on alternate days. The second group received ZEA (2.5 mg/kg) on alternate days plus oral saffron daily (50 mg/kg). The third group was treated with a vehicle of 1% dimethyl sulfoxide (DMSO) on alternate days, as a control. Ten mice were euthanized from each group at 30, 60, and 90 days of treatment. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol ($E_2$), and progesterone (P) were assessed. The uterus and ovaries were examined for changes in size or morphology. Results: Serum levels of LH, FSH, $E_2$, and P in the female mice treated with ZEA plus saffron were significantly higher than in those treated with ZEA alone, and were not significantly different from those treated with 1% DMSO. The female mice treated with ZEA alone showed a reduction in size of the uterus and abnormal architecture of the ovaries. Conclusion: The administration of saffron to female mice resulted in a significant reduction in ZEA-induced alterations in reproductive hormone levels, the size of the uterus, and the morphology of the ovaries.

키워드

참고문헌

  1. Bergman A, Heindel JJ, Jobling S, Kidd KA, Zoeller RT. State of the science of endocrine disrupting chemicals 2012: summary for decision-makers. Geneva: World Health Organization; 2013.
  2. Escriva L, Font G, Manyes L. In vivo toxicity studies of Fusarium mycotoxins in the last decade: a review. Food Chem Toxicol 2015;78:185-206. https://doi.org/10.1016/j.fct.2015.02.005
  3. Gallo D, Cantelmo F, Distefano M, Ferlini C, Zannoni GF, Riva A, et al. Reproductive effects of dietary soy in female Wistar rats. Food Chem Toxicol 1999;37:493-502. https://doi.org/10.1016/S0278-6915(99)00033-2
  4. Rosselli M, Reinhart K, Imthurn B, Keller PJ, Dubey RK. Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function. Hum Reprod Update 2000;6:332-50. https://doi.org/10.1093/humupd/6.4.332
  5. Whitten PL, Patisaul HB. Cross-species and interassay comparisons of phytoestrogen action. Environ Health Perspect 2001;109 Suppl 1:5-20.
  6. Tapiero H, Ba GN, Tew KD. Estrogens and environmental estrogens. Biomed Pharmacother 2002;56:36-44. https://doi.org/10.1016/S0753-3322(01)00155-X
  7. Malekinejad H, Maas-Bakker RF, Fink-Gremmels J. Bioactivation of zearalenone by porcine hepatic biotransformation. Vet Res 2005;36:799-810. https://doi.org/10.1051/vetres:2005034
  8. Dusza L, Ciereszko R, Skarzynski DJ, Nogowski L, Opalka M, Kaminska B, et al. Mechanism of phytoestrogens action in reproductive processes of mammals and birds. Reprod Biol 2006;6 Suppl 1:151-74.
  9. Abbes S, Salah-Abbes JB, Ouanes Z, Houas Z, Othman O, Bacha H, et al. Preventive role of phyllosilicate clay on the immunological and biochemical toxicity of zearalenone in Balb/c mice. Int Immunopharmacol 2006;6:1251-8. https://doi.org/10.1016/j.intimp.2006.03.012
  10. Benassayag C, Perrot-Applanat M, Ferre F. Phytoestrogens as modulators of steroid action in target cells. J Chromatogr B Analyt Technol Biomed Life Sci 2002;777:233-48. https://doi.org/10.1016/S1570-0232(02)00340-9
  11. Poor M, Kunsagi-Mate S, Balint M, Hetenyi C, Gerner Z, Lemli B. Interaction of mycotoxin zearalenone with human serum albumin. J Photochem Photobiol B 2017;170:16-24. https://doi.org/10.1016/j.jphotobiol.2017.03.016
  12. Hou YJ, Zhao YY, Xiong B, Cui XS, Kim NH, Xu YX, et al. Mycotoxincontaining diet causes oxidative stress in the mouse. PLoS One 2013;8:e60374. https://doi.org/10.1371/journal.pone.0060374
  13. National Toxicology Program. Carcinogenesis bioassay of zearalenone (CAS No. 17924-92-4) in F344/N rats and B6C3F1 mice (FEED study). Natl Toxicol Program Tech Rep Ser 1982;235:1-155.
  14. Zinedine A, Soriano JM, Molto JC, Manes J. Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food Chem Toxicol 2007;45:1-18. https://doi.org/10.1016/j.fct.2006.07.030
  15. Ahmad B, Chouhan S, Shrivastava VK. Effect of zearalenone (Mycoestrogen) on morphometrics of female mice and ameliorative role of saffron. Egypt Acad J Biol Sci B Zool 2015;7:1-12.
  16. Nakamura U, Rudolf FO, Pandey K, Kadokawa H. The non-steroidal mycoestrogen zeranol suppresses luteinizing hormone secretion from the anterior pituitary of cattle via the estradiol receptor GPR30 in a rapid, non-genomic manner. Anim Reprod Sci 2015;156:118-27. https://doi.org/10.1016/j.anireprosci.2015.03.009
  17. Kim IH, Son HY, Cho SW, Ha CS, Kang BH. Zearalenone induces male germ cell apoptosis in rats. Toxicol Lett 2003;138:185-92. https://doi.org/10.1016/S0378-4274(02)00405-8
  18. Sambuu R, Takagi M, Namula Z, Nii M, Taniguchi M, Uno S, et al. Effects of long-term in vitro exposure of ejaculated boar sperm to zearalenone and ${\alpha}$-zearalenol in sperm liquid storage medium. Anim Sci J 2013;84:28-34. https://doi.org/10.1111/j.1740-0929.2012.01033.x
  19. Asai A, Nakano T, Takahashi M, Nagao A. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem 2005;53:7302-6. https://doi.org/10.1021/jf0509355
  20. Giaccio M. Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr 2004;44:155-72. https://doi.org/10.1080/10408690490441433
  21. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother 2018;98:333-7. https://doi.org/10.1016/j.biopha.2017.12.077
  22. Mokhtari M, Sharifi E, Daneshi A. Effects of hydro-alcoholic extract of red dried stigmas of Crocus sativus L. flowers (saffron) on the levels of pituitary-ovary hormones and folliculogenesis in rats. Int J Fertil Steril 2010;3:185-90.
  23. Szafranska B, Ziecik A, Okrasa S. Primary antisera against selected steroids or proteins and secondary antisera against gammaglobulins: an available tool for studies of reproductive processes. Reprod Biol 2002;2:187-204.
  24. Wu J, Shao S, Zhou F, Wen S, Chen F, Han X. Reproductive toxicity on female mice induced by microcystin-LR. Environ Toxicol Pharmacol 2014;37:1-6. https://doi.org/10.1016/j.etap.2013.10.012
  25. Guney M, Demirin H, Oral B, Ozguner M, Bayhan G, Altuntas I. Ovarian toxicity in rats caused by methidathion and ameliorating effect of vitamins E and C. Hum Exp Toxicol 2007;26:491-8. https://doi.org/10.1177/0960327106077505
  26. Milano GD, Becu-Villalobos D, Tapia MO. Effects of long-term zearalenone administration on spermatogenesis and serum luteinizing hormone, follicle-stimulating hormone, and prolactin values in male rats. Am J Vet Res 1995;56:954-8.
  27. Collins TF, Sprando RL, Black TN, Olejnik N, Eppley RM, Alam HZ, et al. Effects of zearalenone on in utero development in rats. Food Chem Toxicol 2006;44:1455-65. https://doi.org/10.1016/j.fct.2006.04.015
  28. Whitten PL, Naftolin F. Reproductive actions of phytoestrogens. Baillieres Clin Endocrinol Metab 1998;12:667-90. https://doi.org/10.1016/S0950-351X(98)80010-4
  29. Goldman JM, Cooper RL, Edwards TL, Rehnberg GL, McElroy WK, Hein JF. Suppression of the luteinizing hormone surge by chlordimeform in ovariectomized, steroid-primed female rats. Pharmacol Toxicol 1991;68:131-6. https://doi.org/10.1111/j.1600-0773.1991.tb02050.x
  30. Hooshmandi Z, Rohani AH, Eidi A, Fatahi Z, Golmanesh L, Sahraei H. Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal. Pharm Biol 2011;49:947-54. https://doi.org/10.3109/13880209.2011.558103
  31. Hemmati M, Asghari S, Zohoori E, Karamian M. Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: correlation with serum adiponectin level. Pak J Pharm Sci 2015;28:2095-9.
  32. Dehghan F, Hajiaghaalipour F, Yusof A, Muniandy S, Hosseini SA, Heydari S, et al. Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo. Sci Rep 2016;6:25139. https://doi.org/10.1038/srep25139
  33. Amin B, Nakhsaz A, Hosseinzadeh H. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice. Avicenna J Phytomed 2015;5:458-68.
  34. Hashimova UF, Kamilova NK, Babaev KF, Shukurova PA, Hasanova SI, Abbasov RY. Effects of saffron (Crocus sativus l. iridaceae) on blood level of follicle-stimulating hormone, and number and dynamics of body weight of offspring in female rats. Adv Gerontol 2017;30:436-41.
  35. Groothuis PG, Dassen HH, Romano A, Punyadeera C. Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human. Hum Reprod Update 2007;13:405-17. https://doi.org/10.1093/humupd/dmm009
  36. Nelson JF, Felicio LS, Osterburg HH, Finch CE. Altered profiles of estradiol and progesterone associated with prolonged estrous cycles and persistent vaginal cornification in aging C57bl/6J mice. Biol Reprod 1981;24:784-94. https://doi.org/10.1095/biolreprod24.4.784

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  1. Detoxification Strategies for Zearalenone Using Microorganisms: A Review vol.7, pp.7, 2018, https://doi.org/10.3390/microorganisms7070208
  2. Effects of zearalenone on genital organ development, serum immunoglobulin, antioxidant capacity, sex hormones and liver function of prepubertal gilts vol.189, pp.None, 2018, https://doi.org/10.1016/j.toxicon.2020.11.005
  3. Scutellarin protects mouse ovarian granulosa cells from injury induced by the toxin zearalenone vol.12, pp.3, 2018, https://doi.org/10.1039/d0fo02711a
  4. Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review vol.13, pp.6, 2018, https://doi.org/10.3390/toxins13060373
  5. The Effects of a Saffron Extract (affron®) on Menopausal Symptoms in Women during Perimenopause: A Randomised, Double-Blind, Placebo-Controlled Study vol.27, pp.2, 2021, https://doi.org/10.6118/jmm.21002
  6. Food Mycotoxins: Dietary Interventions Implicated in the Prevention of Mycotoxicosis vol.1, pp.10, 2018, https://doi.org/10.1021/acsfoodscitech.1c00220
  7. Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury vol.227, pp.None, 2018, https://doi.org/10.1016/j.ecoenv.2021.112865