PENGARUH PAPARAN GENISTEIN TERHADAP MOTORIK ZEBRAFISH (Danio rerio) MELALUI PENGAMATAN EKSPRESI TIROSIN HIDROKSILASE DAN RESEPTOR ESTROGEN

Authors

  • Hanif Hanif Fakultas Kedokteran, Universitas Brawijaya
  • Habiba Aurora Universitas Brawijaya

DOI:

https://doi.org/10.21776/ub.majalahkesehatan.2021.008.01.1

Keywords:

genistein, motorik, reseptor estrogen, tirosin hidroksilase, zebrafish

Abstract

Motorik dipengaruhi oleh neuron dopaminergik pada otak, yang maturasi fungsi dan morfologi pada masa awal pembentukan dipengaruhi oleh kadar estrogen. Pemberian genistein sebagai fitoestrogen dengan dosis tinggi pada masa awal perkembangan menyebabkan hambatan perkembangan motorik pada zebrafish. Penelitian ini bertujuan membuktikan mekanisme kerja genistein pada neuron dopaminergik, melalui pengamatan ekspresi tirosin hidroksilase (TH), respons taktil, dan tes lokomotor pada embrio zebrafish. Embrio zebrafish dibagi menjadi enam kelompok, yaitu kontrol (DMSO 0,05%), paparan genistein 5 µM, paparan genistein 10 µM, paparan ICI 182.780 10 µM, paparan genistein 5 µM + ICI 182.780 10 µM, paparan genistein 10 µM + ICI 182.780 10 µM dan diamati pada 2, 24,48, 72,120 dan 144 hpf (hours post fertilization). Pengamatan ekspresi TH dilakukan pada 48 hpf, respons taktil pada 72 hpf dan tes lokomotor pada 144 hpf. Hasil penelitian ini menunjukkan bahwa pemberian antagonis estrogen ICI 182.780 memperbaiki ekspresi TH, respon taktil dan kemampuan lokomotor embrio zebrafish secara optimal pada zebrafish yang dipapar genistein 5 µM.

 

Author Biographies

Hanif Hanif, Fakultas Kedokteran, Universitas Brawijaya

departemen anestesiologi dan terapi intensif,

Habiba Aurora, Universitas Brawijaya

Departemen Radiologi, Fakultas Kedokteran

References

Gore AC, Krishnan K, Reilly MP. Endocrine-Disrupting Chemicals: Effects on Neuroendocrine Systems and the Neurobiology of Social Behavior. Hormones and Behaviour. 2019; 111:7-22. DOI: 10.1016/j.yhbeh.2018.11.006.

Balaguer P, Delfosse V, Grimaldi M, Bourguet W, Structural and Functional Evidences for the Interactions between Nuclear Hormone Receptors and Endocrine Disruptors at Low Doses. Comptes Rendus Biologies. 2017; 340:412-420.

Schiller V, Wichmann A, Kriehuber R, Muth-Kohne E, Giesy JP, Hecker M, Fenske M. Studying the Effects of Genistein on Gene Expression of Fish Embryos as an Alternative Testing Approach for Endocrine Disruption. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology. 2013; 157:41-53.

Licata P, Tardugno R, Pergolizzi S, Capillo G, Aragona M, Colombo A, Gervasi T, Pellizzeri V, Cicero N, Calo M. In Vivo Effects of PCB-126 and Genistein on Vitellogenin Expression in Zebrafish. Natural Product Research. 2019; 33(17):2507-2514. DOI: 10.1080/14786419.2018.1455048.

Zielinska KA., The Influence of Environmental Estrogens on Early-Life Stage Zebrafish Development. Doctoral Thesis. Galway Ireland: National University of Ireland. 2013. Retrieved from http://hdl.handle.net/10379/3569.

Notch EG & Mayer GD. Efficacy of Pharmacological Estrogen Receptor Antagonists in Blocking Activation of Zebrafish Estrogen Receptors. General and Comparative Endocrinology. 2011; 173:183–189.

Aurora H, Lyrawati D. Efek Waktu Paparan Genistein terhadap Pembentukan Jantung Embrio Zebrafish. Jurnal Kedokteran Brawijaya. 2014; 28(1):22-25.

Lam SH, Lee SGP, Lin CY, Thomsen JS, Fu PY, Murthy KRK, Li H, Govindarajan KR, Nick LCH, Bourque G, Gong Z, Lufkin T, Liu ET, Mathavan S. Molecular Conservation of Estrogen-Response Associated with Cell Cycle Regulation, Hormonal Carcinogenesis and Cancer in Zebrafish and Human Cancer Cell Lines. BMC Medical Genomics. 2011; 4(41):1-15.

Sarasquete C, Úbeda-Manzanaro M & Ortiz-Delgado JB. Effects of the Isoflavone Genistein in Early Life Stages of the Senegalesesole, Solea senegalensis: Role of the Surviving and Proliferation Versus Apoptosis Pathways. BMC Vet Res. 2018; 14:16. DOI: doi.org/10.1186/s12917-018-1333-3.

Sassi-Messai S, Gibert Y, Bernard L, Nishio S, Ferri Lagneau KF, Molina J, Andersson-Lendahl M, Benoit G, Balaguer P, & Laudet V. The Phytoestrogen Genistein Affects Zebrafish Development through Two Different Pathways. PloS One. 2009; 4(3):e4935. DOI: doi.org/10.1371/journal.pone.0004935.

Kim DJ, Seok SH, Baek MW, Lee HY, Na YR, Park SH, Lee HK, Dutta NK, Kawakami K, Park JH. Developmental Toxicity and Brain Aromatase Induction by High Genistein Concentrations in Zebrafish Embryos. Toxicology Mechanisms and Methods. 2009; 19(3):251256, DOI: 10.1080/1537651080253330.

Bakkiyanathan A, Joseph AM, Tharani L, Malathi R. Genistein, the Phytoestrogen Induces Heart-and-Soul (has) Phenotypes in Zebrafish Embryo. Journal of Developmental Biology and Tissue Engineering. 2010; 2(2):18-22.

Brown AC, Stevenson LM, Leonard HM, Nieves-Puigdoller K, Clotfelter ED. Phytoestrogens β-Sitosterol and Genistein have Limited Effects on Reproductive Endpoints in a Female Fish, Betta Splendens. Biomed Res Int. 2014; 2014:681396.

Vosges M, Kah O, Hinfray N, Chadili E, Le Page Y, Combarnous Y, Porcher JM, Brion F. 17α-Ethinylestradiol and Nonylphenol Affect the Development of Forebrain GnRH Neurons through an Estrogen Receptor-Dependent Pathway. Reprod. Toxicol. 2012; 33 (2):198–204.

Bertotto LB, Dasgupta S, Vliet S, Dudley S, Gan J, Voiz DC, Schlenk D. Evaluation of the Estrogen Receptor Alpha as a Possible Target of Bifenthrin Effects in the Estrogenic and Dopaminergic Signaling Pathways in Zebrafish Embryos. Sci Total Environ. 2019; 651 (2): 2424-2431.

Kyuhou S. Preventive Effects of Genistein on Motor Dysfunction Following 6-Hydroxydopamine Injection in Ovariectomized Rats. Neuroscience Letters. 2008; 448:10–14.

Song Z, Yang H, Peckham EM, Becker JB. Estradiol-Induced Potentiation of Dopamine Release in Dorsal Striatum Following Amphetamine Administration Requires Estradiol Receptors and mGlu5. ENeuro. 2019; 6(1): e0446-18.2019 1–8.

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Published

2021-04-06