Genistein To Decrease Matrix Metalloproteinase-2 (Mmp-2) And Matrix Metalloproteinase-9 (Mmp-9) Levels In Peritoneal Fluid Of Endometriosis On Mice Model

Latar Belakang: Matrix metalloproteinases (MMPs) mempengaruhi progesivitas endometriosis, dalam invasi, perkembangan dan metastasis endometriosis. Penururan kadar MMP-2 dan MMP-9 merupakan terapi yang tepat untuk kasus endometriosis menggunakan terapi hormonal alami yaitu genistein. Tujuan: Penelitian ini bertujuan untuk mengetahui pemberian genistein dapat menurunkan kadar MMP-2 dan MMP-9 dalam cairan peritoneal mencit (Mus musculus) model endometriosis. Metode: Penelitian ini merupakan penelitian eksperimental yang dilakukan di Laboratorium Fisiologi Reproduksi Embriologi Fakultas Kedokteran Hewan Universitas Airlangga Surabaya dan Laboratorium Fisiologi Fakultas Kedokteran Universitas Brawijaya Malang. Sampel menggunakan mencit (Mus musculus) model endometriosis. Penelitian dibagi menjadi 8 kelompok, yaitu : kontrol negatif, kontrol positif dan perlakuan pemberian genistein dosis 50 mg/hari, 100 mg/hari, 200 mg/hari, 300 mg/hari, 400 mg/hari, 500 mg/hari. Pengukuran kadar MMP-2 dan MMP-9 menggunakan ELISA kit. Data hasil pengamatan dianalisis dengan uji ANOVA, Tukey dan Regresi. Hasil: Genistein mampu menurunkan kadar MMP-2 terendah pada dosis 50 mg/hari (5.61±0.69 ng/mL), 100 mg/hari (4.91±0.59 ng/mL) dan 400 mg/hari (4.95±0.32 ng/mL) bila dibandingkan dengan perlakuan dosis yang lain. Genistein mampu menurunkan kadar MMP-9 terendah pada dosis 50 mg/hari (1.69±0.45 ng/mL), 100 mg/hari (1.29±0.32 ng/mL), 200 mg/hari (1.84±0.25 ng/mL) dan 400 mg/hari (1.42±0.11 ng/mL) bila dibaningkan dengan perlakuan dosis yang lain. Kesimpulan: Genistein dapat menurunkan kadar MMP-2 dan MMP-9 dalam cairan peritoneal mencit (Mus musculus) model endometriosis. Saran: Perlu studi lanjut untuk melihat pengaruh genistein pada hewan coba kelinci Kata Kunci: Endometriosis, Genistein, MMP-2, MMP-9

Background: Matrix metalloproteinases (MMPs) affect the progression of endometriosis, in the invasion , development , and metastasis of endometriosis. Reducing levels of MMP-2 and MMP-9 is an appropriate therapy for endometriosis cases using natural hormonal therapy, namely genistein. Purpose: To know the effect of genistein on the level of MMP-2 and MMP-9 in peritoneal fluid of endometriosis mice model.

The design of this study was experimental, had been performed in Reproductive Physiology and Embryology Laboratory, Veterinary Medical Faculty of Airlangga University Surabaya and Physiology Laboratory, Medical Faculty of Brawijaya University Malang. The animal model was divided the 8 groups: negative group ,positive group, and treated group with genistein doses of 50 mg/day, 100 mg/day, 200 mg/day, 300 mg/day, 400 mg/day, and 500 mg /day (human dose). The measurement of MMP-2 and MMP-9 levels using ELISA kits. The data were analyzed with ANOVA, Tukey, and Regression tests.

Genistein was able to decrease the MMP-2 level in the lowest dose 50 mg/day (5.61±0.69 ng/mL), 100 mg/day (4.91±0.59 ng/mL) and 400 mg/day (4.95±0.32 ng/mL) when compared with other treatment dose. Genistein was able to decrease the MMP-9 level in the lowest dose 50 mg/day (1.69±0.45 ng/mL), 100 mg/day (1.29±0.32 ng/mL), 200 mg/day (1.84±0.25 ng/ mL) and 400 mg/day (1.42±0.11 ng/mL) when compared with other treatment doses.

Genistein may decrease MMP-2 and MMP-9 levels in peritoneal fluid of endometriosis mice model. Suggestion: Further study is needed to see the effect of genistein on rabbit experimental animals.

Endometriosis, Genistein, MMP-2, MMP-9

Full Text: PDFReferences Adamyan, LV, Manukyan, LM, Loginova, ON, Arslanyan, KN, & Zayratyants, VO(2020). The role of matrix metalloproteinases in the pathogenesis of endometriosis (Literature review). In Russian Journal of Human Reproduction (Vol. 26, Issue 2, pp. 95–103). https://doi.org/10.17116/repro20202602195 Banerjee, S., Li, Y., Wang, Z., & Sarkar, FH (2008). Multi-targeted therapy of cancer by genistein. Cancer Letters , 269 (2), 226–242. https://doi.org/10.1016/j.canlet.2008.03.052 Brinckerhoff, CE (2017). Regulation of Matrix Metalloproteinase (MMP) Gene Expression. In Matrix Metalloproteinases in Health and Disease (pp. 31–63). https://doi.org/10.1142/9789813207554_0003 Collette, T., Maheux, R., Mailloux, J., & Akoum, A. (2006). Increased expression of matrix metalloproteinase-9 in the eutopic endometrial tissue of women with endometriosis. Human Reproduction , 21 (12), 3059–3067. https://doi.org/10.1093/humrep/del297 Fassbender, A., Dorien, O., De Moor, B., Waelkens, E., Meuleman, C., Tomassetti, C., Peeraer, K., & D'Hooghe, T. (2014). Biomarkers of endometriosis. Endometriosis: Pathogenesis and Treatment , 99 (4), 321–339. https://doi.org/10.1007/978-4-431-54421-0_20 Kayisli, UA, Aksu, CAH, Berkkanoglu, M., & Arici, A. (2002). Estrogenicity of isoflavones on human endometrial stromal and glandular cells. In Journal of Clinical Endocrinology and Metabolism (Vol. 87, Issue 12, pp. 5539–5544). https://doi.org/10.1210/jc.2002-020716 Lakshman, M., Xu, L., Ananthanarayanan, V., Cooper, J., Takimoto, CH, Helenowski, I., Pelling, JC, & Bergan, RC (2008). Dietary genistein inhibits metastasis of human prostate cancer in mice. In Cancer Research (Vol. 68, Issue 6, pp. 2024–2032). https://doi.org/10.1158/0008-5472.CAN-07-1246 Leyland, N., Casper, R., Laberge, P., Singh, SS, Allen, L., Arendas, K., Allaire, C., Awadalla, A., Best, C., Contestabile, E., Dunn , S., Heywood, M., Leroux, N., Potestio, F., Rittenberg, DA, Soucy, R., Wolfman, WL, & Senikas, V. (2010). Endometriosis: Diagnosis and Management. Journal of Obstetrics and Gynecology Canada , 32 (7), S1–S3. https://doi.org/10.1016/S1701-2163(16)34589-3 Mendis, E., Kim, MM, Rajapakse, N., & Kim, SK (2009). The inhibitory mechanism of a novel cationic glucosamine derivative against MMP-2 and MMP-9 expressions. In Bioorganic and Medicinal Chemistry Letters (Vol. 19, Issue 10, pp. 2755–2759). https://doi.org/10.1016/j.bmcl.2009.03.126 Noori-Daloii, MR, Saffari, M., Saydi Dinekabodi, O., Rahmani, B., Noori-Daloii, AR, Salehi, AH, & Ghazarian, A. (2012). Study of antimetastatic effect of genistein through inhibition of expression of matrix metalloproteinase in A-549 cell line. Journal of Sciences, Islamic Republic of Iran , 23 (2), 115–122. Prakash, D., & Gupta, C. (2011). Role of phytoestrogens as nutraceuticals in human health: A review. BioTechnology: An Indian Journal , 5 (3), 171–178. Sha, GH, & Lin, SQ (2008). Genistein inhibits proliferation of human endometrial endothelial cells in vitro. Chinese Medical Sciences Journal , 23 (1), 49–53. https://doi.org/10.1016/S1001-9294(09)60010-9 Shaco-Levy, R., Sharabi, S., Benharroch, D., Piura, B., & Sion-Vardy, N. (2008). Matrix metalloproteinases 2 and 9, E-cadherin, and -catenin expression in endometriosis, lowgrade endometrial carcinoma and nonneoplastic eutopic endometrium. In European Journal of Obstetrics and Gynecology and Reproductive Biology (Vol. , Issue 2, pp. 226–232). https://doi.org/10.1016/j.ejogrb.2008.01.004 Soares, SR, Martínez-Varea, A., Hidalgo-Mora, J. J., & Pellicer, A. (2012). Pharmacologic therapies in endometriosis: A systematic review. Fertility and Sterility , 98 (3), 529–555. https://doi.org/10.1016/j.fertnstert.2012.07.1120 Sutrisno. 2014. The Effect of Implant Origin on the Incidence of Peritoneal Endometriosis, A Study to Design a Mice Model of Endometriosis. Laboratory of Obstetrics and Gynecology FK Brawijaya University, Malang Sutrisno, S., Mastryagung, D., Khairiyah, R. , Tridiyawati , F., Dewi, N., Hidayati, D., Noorhamdani, N., Santoso, S., 2014. The effects of genistein on estrogen receptor expression , cell proliferation and apoptosis in endometriosis cell culture. Journal of Experimental and Integrative Medicine. 4 (3 ) : 1-6 Sutrisno, S., Mariyani, M., Herawati I., Rinata, E. , Jehanara , J., Yueniwati, Y., Nurdiana, N., Noorhamdani, N., Santoso, S., 2014. The effects of genistein as inflammatory and antiangiogenesis in primary endometriosis cell culture. Asian Pacific Journal of Reproduction . 3 (4 ) : 1-6 Weigel, MT, Krämer, J., Schem, C., Wenners, A. , Alkatout , I., Jonat, W., Maass, N., & Mundhenke, C. (2012). Differential expression of MMP-2, MMP-9 and PCNA in endometriosis and endometrial carcinoma. European Journal of Obstetrics Gynecology and Reproductive Biology , 160 (1), 74–78. https://doi.org/10.1016/j.ejogrb.2011.09.040 Yavuz, E., Oktem, M., Ensiler, I., Toru, SA, and Zeyneloglu, HB, 2006. Genistein Causes Regression of Endometriotic Implants in the Rat Model. Fertility and Sterility . 88(2 ) : 1129-1134 Zhang, H., Li, M., Wang, F., Liu, S., Li, J., Wen, Z. , & Zhao, X. (2010). Endometriotic epithelial cells induce MMPs expression in endometrial stromal cells via an NFB-dependent pathway. In Gynecological Endocrinology (Vol. 26, Issue 6, pp. 456–467). https://doi.org/10.3109/09513590903366988 DOI: https://doi.org/10.33024/jkm.v8i1.5847 Refbacks - There are currently no refbacks. Copyright (c) 2022 Jurnal Kebidanan Malahayati Policies | Submissions | Other | | Focus and Scope Section Policies Peer Review Process Publication Frequency Open Access Policy | Online Submissions Author Guidelines Copyright Notice Privacy Statement Author Fees | Journal Sponsorship Journal History Site Map About this Publishing System |