DOI QR코드

DOI QR Code

Safety effect of fermented oyster extract on the endocrine disruptor assay in vitro and in vivo

  • Lee, Hyesook (Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Hwangbo, Hyun (Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Ji, Seon Yeong (Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Oh, Seyeon (Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Byun, Kyung-A (Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Park, Joung-Hyun (Ocean Fisheries & Biology Center, Marine Bioprocess Co., Ltd.) ;
  • Lee, Bae-Jin (Ocean Fisheries & Biology Center, Marine Bioprocess Co., Ltd.) ;
  • Kim, Gi-Young (Department of Marine Life Science, Jeju National University) ;
  • Choi, Yung Hyun (Department of Biochemistry, College of Korean Medicine, Dong-eui University)
  • 투고 : 2021.09.17
  • 심사 : 2021.09.28
  • 발행 : 2021.10.31

초록

Oyster (Crassostrea gigas) is a marine bivalve mollusk widely distributed in coastal areas, and have been long widely used in industrial resources. Several studies demonstrated that fermented oyster (FO) extract attribute to bone health, but whether administration of FO play as an endocrine disruptor has not been studied. Therefore, in the present study, we investigated the effect of FO on the endocrine system in vitro and in vivo. As the results of the competitive estrogen receptor (ER) and androgen receptor (AR) binding affinities, FO was not combined with ER-α, ER-β, and AR. However, 17β-estradiol and testosterone, used as positive control, were interacted with ER and AR, respectively. Meanwhile, oral administration of 100 mg/kg and 200 mg/kg of FO doesn't have any harmful effect on the body weight, androgen-dependent sex accessory organs, estrogen-dependent-sex accessory organs, kidney, and liver in immature rats. In addition, FO supplementation has no effect on the serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and 17β-estradiol. However, the relative weight of androgen- and estrogen-dependent organs were significantly increased by subcutaneously injection of 4.0 mg/kg of testosterone propionate (TP) and by orally administration of 1.0 ㎍ of 17α-ethynyl estradiol (EE) in immature male and female rats, respectively. Furthermore, TP and EE administration markedly decreased the serum LH and FSH levels, which are similar those of mature Sprague-Dawley (SD) rat. Furthermore, the testosterone and 17β-estradiol levels were significantly enhanced in TP and EE-treated immature rats. Taken together, our findings showed that FO does not interact with ER and AR, suggesting consequentially FO does not play as a ligand for ER and AR. Furthermore, oral administration of FO did not act as an endocrine disruptor including androgenic activity, estrogenic activity, and abnormal levels of sex hormone, indicating FO may ensure the safety on endocrine system to develop dietary supplement for bone health.

키워드

과제정보

This research was part of the project titled "Development of functional food products with natural materials derived from marine resources" funded by the Ministry of Oceans and Fisheries, Korea (grant no.:20170285).

참고문헌

  1. Argente J. Challenges in the management of short stature. Horm Res Paediatr. 2016;85:2-10. https://doi.org/10.1159/000442350
  2. Billon-Gales A, Krust A, Fontaine C, Abot A, Flouriot G, Toutain C, et al. Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing. Proc Natl Acad Sci USA. 2011;108:13311-6. https://doi.org/10.1073/pnas.1105632108
  3. Calafat AM, Needham LL. Human exposures and body burdens of endocrine-disrupting chemicals. In: Gore AC, editor. Endocrine-disrupting chemicals: from basic research to clinical practice. Totowa, NJ: Humana Press; 2007. p.253-68.
  4. Coringa R, de Sousa EM, Botelho JN, Diniz RS, de Sa JC, da Cruz MCFN, et al. Bone substitute made from a Brazilian oyster shell functions as a fast stimulator for bone-forming cells in an animal model. PLOS ONE. 2018;13:e0198697. https://doi.org/10.1371/journal.pone.0198697
  5. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocr Rev. 2009;30:293-342. https://doi.org/10.1210/er.2009-0002
  6. Dickerson SM, Gore AC. Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle. Rev Endocr Metab Disord. 2007;8:143-59. https://doi.org/10.1007/s11154-007-9048-y
  7. Huh K, Nah WH, Xu Y, Park MJ, Gye MC. Effects of recombinant human growth hormone on the onset of puberty, leydig cell differentiation, spermatogenesis and hypothalamic KISS1 expression in immature male rats. World J Mens Health. 2021;39:381-8. https://doi.org/10.5534/wjmh.200152
  8. Ihn HJ, Kim JA, Lim S, Nam SH, Hwang SH, Lim J, et al. Fermented oyster extract prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis. Nutrients. 2019;11:1392. https://doi.org/10.3390/nu11061392
  9. Jeong A, Park BC, Kim HY, Choi JY, Cheon J, Park JH, et al. Efficacy and safety of fermented oyster extract for height of children with short stature: a randomized placebo-controlled trial. Integr Med Res. 2021;10:100691. https://doi.org/10.1016/j.imr.2020.100691
  10. Jeong JW, Choi SH, Han MH, Kim GY, Park C, Hong SH, et al. Protective effects of fermented oyster extract against RANKL-induced osteoclastogenesis through scavenging ROS generation in RAW 264.7 cells. Int J Mol Sci. 2019;20:1439. https://doi.org/10.3390/ijms20061439
  11. Kanno J, Onyon L, Peddada S, Ashby J, Jacob E, Owens W. The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies. Environ Health Perspect. 2003;111:1530-49. https://doi.org/10.1289/ehp.5780
  12. Kamp GA, Waelkens JJJ, de Muinck Keizer-Schrama SMPF, Delemarre-Van de Waal HA, Verhoeven-Wind L, Zwinderman AH, et al. High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature. Arch Dis Child. 2002;87:215-20. https://doi.org/10.1136/adc.87.3.215
  13. Kleinstreuer NC, Ceger PC, Allen DG, Strickland J, Chang X, Hamm JT, et al. A curated database of rodent uterotrophic bioactivity. Environ Health Perspect. 2016;124:556-62. https://doi.org/10.1289/ehp.1510183
  14. Lee H, Hwangbo H, Ji SY, Kim MY, Kim SY, Kim DH, et al. Gamma aminobutyric acid-enriched fermented oyster (Crassostrea gigas) increases the length of the growth plate on the proximal tibia bone in Sprague-Dawley rats. Molecules. 2020a;25:4375. https://doi.org/10.3390/molecules25194375
  15. Lee H, Hwang-Bo H, Ji SY, Kim MY, Kim SY, Woo M, et al. Effect of fermented oyster extract on growth promotion in Sprague-Dawley rats. Integr Med Res. 2020b;9:100412. https://doi.org/10.1016/j.imr.2020.100412
  16. Lee YK, Jung SK, Chang YH, Kwak HS. Highly bioavailable nanocalcium from oyster shell for preventing osteoporosis in rats. Int J Food Sci Nutr. 2017;68:931-40. https://doi.org/10.1080/09637486.2017.1307948
  17. Molagoda IMN, Karunarathne WAHM, Choi YH, Park EK, Jeon YJ, Lee BJ, et al. Fermented oyster extract promotes osteoblast differentiation by activating the Wnt/β-catenin signaling pathway, leading to bone formation. Biomolecules. 2019;9:711. https://doi.org/10.3390/biom9110711
  18. OECD. Test No. 441: Hershberger bioassay in rats. Paris, France: OECD; 2009a.
  19. OECD. Test No. 440: Uterotrophic bioassay in rats. Paris, France: OECD; 2009b.
  20. OECD. Hershberger bioassay in rats (H assay) (OECD TG 441) (including OECD GD 115 on the weanling Hershberger bioassay: revised guidance document 150 on standardised test guidelines for evaluating chemicals for endocrine disruption. Paris, France: OECD; 2018. p.463-76.
  21. Owens W, Koeter HBWM. The OECD program to validate the rat uterotrophic bioassay: an overview. Environ Health Perspect. 2003;111:1527-9. https://doi.org/10.1289/ehp.6413
  22. Rosenfeld RG. Insulin-like growth factors and the basis of growth. N Engl J Med. 2003;349:2184-6. https://doi.org/10.1056/NEJMp038156
  23. Souza FM, Collett-Solberg PF. Adverse effects of growth hormone replacement therapy in children. Arq Bras Endocrinol Metabol. 2011;55:559-65. https://doi.org/10.1590/S0004-27302011000800009
  24. US Environmental Protection Agency. Standard evaluation procedure hershberger assay OCSPP 890.1400. Washington, DC: US Environmental Protection Agency; 2011.
  25. Wit JM, Rekers-Mombarg LTM, Dutch Growth Hormone Advisory Group. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab. 2002;87:604-11. https://doi.org/10.1210/jc.87.2.604
  26. Wit JM, Rekers-Mombarg LTM, Cutler GB Jr, Crowe B, Beck TJ, Roberts K, et al. Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect. J Pediatr. 2005;146:45-53. https://doi.org/10.1016/j.jpeds.2004.08.055
  27. Xiang XW, Zheng HZ, Wang R, Chen H, Xiao JX, Zheng B, et al. Ameliorative effects of peptides derived from oyster (Crassostrea gigas) on immunomodulatory function and gut microbiota structure in cyclophosphamide-treated mice. Mar Drugs. 2021;19:456. https://doi.org/10.3390/md19080456
  28. Yamasaki K, Sawaki M, Ohta R, Okuda H, Katayama S, Yamada T, et al. OECD validation of the Hershberger assay in Japan: phase 2 dose response of methyltestosterone, vinclozolin, and p,p'-DDE. Environ Health Perspect. 2003;111:1912-9. https://doi.org/10.1289/ehp.6357
  29. Zhao Y, Zheng HX, Xu Y, Lin N. Estrogenic effect of the extract of QingYan formula on reproductive tissues in immature mice. Evid Based Complement Alternat Med. 2019;2019:5493714.
  30. Zhang W, Wei Y, Cao X, Guo K, Wang Q, Xiao X, et al. Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production. J Ethnopharmacol. 2021;264:113382. https://doi.org/10.1016/j.jep.2020.113382