Ekaputra, Aditya Airlangga and dr. Taufig Nur Budaya, Sp.U(k) and Dr., dr., Besut Daryanto, Sp.B, Sp.U(k) and dr. Kenty Wantri Anita, M.Kes, Sp.PA(k) (2022) Pengaruh 'Pemberian Selective Androgen Reseptor ' Modulator (Sarm' Rad140) terhadap Jumlah’ Osteoklas ‘dan Osteoblas pada Tikus Rattus Norvegicus Galur; Wistar dengan Orkidektomi.. Magister thesis, Universitas Brawijaya.
Abstract
Sekitar 174.650 ‘kasus-baru kanker di seluruh dunia pada tahun 2019 diperkirakan sebanyak 20% merupakan kanker prostat, sedangkan di Indonesia jumlah penderita“di- tiga RS pusat pendidikan'(Jakarta, Surabaya dan Bandung) selama’ 8 tahun terakhir adalah-1.102 ‘pasien dengan rerata usia 67,18 tahun: Laboratorium -Patologi - Anatomi RSSA) Malang periode -tahun -2015-2019 melaporkan-kasus -sebanyak -84 -(7,58%) kasus dengan rata-rata wsia 68 tahun; Modalitas kastrasi surgical, seperti orkidektomi dan kastrasi medical sama-sama efektif .dalam mencapai tingkat kastrasi testosteron (<50 ng/dL) dan memiliki efektifitas yang sama dalam mengendalikan kanker. (Garje et al., 2020). Telah diketahui ‘sebelumnya bahwa - osteoblas berperan penting dalam remodeling tulang, sedangkan osteoklas adalah sel yang mendegradasi tulang dan'memediasi pengeroposan- tulang- dalam kondisi patologis’ dengan' 'meningkatkan 'aktivitas resorptifnya. 'Selective Androgen: Receptor Modulator atau SARM adalah kelas ligan reseptor: androgen: yang mengikat reseptor: androgen- dan: mengaktivasi tissue-selective - androgenic. -signaling.-. Terapi-, SARM . RAD140. dipilih . pada penelitian ini untuk mencegah efek samping dari pemberian terapi ADT dengan metode orkidektomi. Desain penelitian ini menggunakan rancangan true ~experimental- randomized post test only control group design secara in vivo. Sampel penelitian yang digunakan yaitu-tikus putih (Rattus norvegicus)-jantan galur-Wistar, ‘usia 3 bulan dengan berat badan 200-250 gram. Osteoblas adalah sel pembentuk tulang khusus yang memiliki peran penting dalam remodeling tulang. Osteoklas adalah sel yang mendegradasi tulang dan memediasi pengeroposan tulang dalam kondisi patologis dengan meningkatkan aktivitas resorptifnya: Osteoblas secara histologis ditandai dengan adanya nukleus bulat di sel basal yang mengandung satu hingga tiga nucleolus, sedangkan osteoklas memiliki_ ciri-ciri morfologi sel yang besar serta memiliki inti yang banyak’(Aminatun et a/., 2019). Osteoblas dan osteoklas dievaluasi'dengan cara penghitungan jumlah sel-dari preparat histopatologi tulang femur tikus“pada“potongan' transversal. Penghitungan 'dilakukan ‘menggunakan mikroskop. cahaya dengan | perbesaran 400x dan’ dalam10x ' lapang -pandang (Syarif et al, 2020; Liu et al., 2017; Mohamed et al., 2016). Analisis data yang digunakan . dalam penelitian ini adalah analisis kuantitatif One: Way ANOVA.. Uji One Way ANOVA digunakan untuk mengetahui signifikansi jumlah osteoblast dan osteoklas setelah pemberian terapi SARM karena skala pengukurannya merupakan skala numerik, jenis hipotesis yang digunakan adalah komparatif, dan jumlah’kelompok ‘perlakuan yang digunakan lebih dari-dua kelompok.
English Abstract
Around 174,650 new cancer cases worldwide in 2019, an estimated 20% are prostate cancer, while in Indonesia the number of sufferers in three educational center hospitals (Jakarta, ‘Surabaya and Bandung) for the past 8 years'is 1,102 patients With an average age of 67.18 years . RSSA Malang Anatomical Pathology Laboratory for-the 2015-2019 period reported 84 cases (7.58%) with an:average age of 68 years. Surgical castration modalities, such as orchidectomy'and medical castration, are-equally: effective in achieving.testosterone, castration-levels (<50 ng/dL) and equally_effective in controlling cancer. (Garje et al., 2020).. It is. known previously that osteoblasts play an important role in bone remodeling, while osteoclasts are cells that degrade bone and mediate bone loss under pathological conditions’ by “increasing 'its resorptive activity. Selective Androgen ‘Receptor Modulators or" SARMs are a class of ‘androgen receptor- ligands that bind to androgen ‘receptors and 'activate tissue-selective androgenic' signaling. SARM RAD140 therapy was chosen in this study to prevent side effects from ADT therapy. using the orchidectomy method. The design of this study used a true experimental-randomized post test only control, group. design.-in vivo. The research sample used was male Wistar rats (Rattus norvegicus), 3 months old, weighing 200-250 grams. Osteoblasts are specialized bone-forming cells-that have an important role in bone remodeling. Osteoclasts are cells that degrade bone and mediate bone loss under pathological conditions' by ‘increasing their resorptive activity. Osteoblasts are histologically characterized by the presence of a rounded nucleus in'the basal cells containing oneto three nucleoli, while osteoclasts have morphological characteristics of large cells and have many nuclei (Aminatun-et al.,-2019). Osteoblasts and osteoclasts were evaluated by counting the number of cells from histopathological preparations of the rat femur on transverse sections. The calculation was carried out using a light microscope with a magnification of 400x and in a field of view of 10x (Syarif et al.,’2020; Liu et'al., 2017, Mohamed et al.. 2016). Data analysis used in this research is One Way ANOVA quantitative analysis. The One Way ANOVA test was used to “determine 'the ' significance of 'the, number 'of ' osteoblasts and osteoclasts after SARM therapy because the: measurement scaleis a numerical scale, the types of hypotheses used are comparative, and the;number of treatment groups used. is more than two groups. Based on the results of the study in the form of the number of osteoblast cells and osteoclast cells using one way analysis of ANOVA (Analysis of Variance), each treatment group obtained a significance value of 0.000 (p <0.05), which means that there is a difference in data on the number of osteoblast cells and osteoclast cells in'mice between treatment groups. . The average number of rat osteoclasts tends UNIVERSITAS 2 & v < w = = =UNIVERSITAS to'increase ‘and the average number of osteoclasts tends to-decrease when given higher doses, ‘so-based on a descriptive ‘assessment of the average number of osteoblast cells and the number of osteoclasts!in rats/at graded doses of SARM RAD140 0.03 mg/day kg, 0.1 mg/kg, 1 mg/kg; 3 mg/kg and 10 mg/kg show,different effects or effects. The: higher.the dose given. will further, increase the number of osteoblast cells, otherwise decrease the number of osteoclast cells. This mechanism involves several cells in the bone, one of which is osteoblasts which can emit androgen receptors and are target cells for testosterone (de Paiva Gongalves ‘et al.; 2021). Almost all studies show that androgens regulate AR expression in osteoblasts. Stromal cells (osteoblast precursors), megakaryocytes, and'endothelial cells in'the bone marrow express/AR: Androgens have been shown torsuppress apoptotic osteoblasts. Androgens stimulate interleukin-18 production and enhance the mitogenic effect of fibroblast growth factor in cultured osteoblasts. General. evidence shows, that _androgens. stimulate osteoblast. differentiation (Mohamad et al., 2016). Based on research by Kearby, et al (2007) which examined the effect of SARM S-4 on preventing bone loss and reducing body fat in ‘ovariectomized rats, it was found that treating cells with SARM S-4 significantly reduced the number of induced multinucleated osteoclasts. by RANK-L-and GM- CSF stimulation. (Kearby: et al;, 2007)
| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | 0422060198 |
| Uncontrolled Keywords: | Osteoblast; Osteoclast, SARM-RAD140 |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.8 Diseases of nervous system and mental disorders |
| Divisions: | Profesi Kedokteran > Spesialis Neurologi, Fakultas Kedokteran |
| Depositing User: | Endang Susworini |
| Date Deposited: | 02 Nov 2023 02:26 |
| Last Modified: | 02 Nov 2023 02:26 |
| URI: | http://repository.ub.ac.id/id/eprint/204209 |
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