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JUDUL
KARYA TULIS AKHIR
PENGARUH EKSTRAK UBIJALAR UNGU (Ipomoea batatas) VARIETAS
ANTIN-3 TERHADAP PENURUNAN KADAR MALONDIALDEHIDA
(MDA) HEPAR TIKUS PUTIH JANTAN (Rattus novergicus) STRAIN
WISTAR YANG DIINDUKSI ISONIAZID DAN RIFAMPISIN
Oleh:
Farahiya Nabila
201010330311078
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG
2014
ii
HASIL PENELITIAN
PENGARUH EKSTRAK UBIJALAR UNGU (Ipomoea batatas) VARIETAS
ANTIN-3 TERHADAP PENURUNAN KADAR MALONDIALDEHIDA
(MDA) HEPAR TIKUS PUTIH JANTAN (Rattus novergicus) STRAIN
WISTAR YANG DIINDUKSI ISONIAZID DAN RIFAMPISIN
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
untuk Memenuhi Salah Satu Persyaratan
dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh:
Farahiya Nabila
201010330311078
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG
2014
iii
iv
v
KATA PENGANTAR
Syukur Alhamdulillah penulis panjatkan kepada Allah SWT atas rahmat
dan hidayah-Nya sehingga penulis dapat menyelesaikan tugas akhir yang berjudul
”Pengaruh Ekstrak Ubijalar Ungu (Ipomoea batatas) Varietas Antin-3
Terhadap Penurunan Kadar Malondialdehida (MDA) Hepar Tikus Putih
Jantan (Rattus novergicus) Strain Wistar Yang Diinduksi Isoniazid dan
Rifampisin” sebagai persyaratan untuk menyelesaikan studi Pendidikan Sarjana
Fakultas Kedokteran Universitas Muhammadiyah Malang.
Peneliti menyadari bahwa penulisan tugas akhir ini terselesaikan karena
adanya bantuan dari berbagai pihak, oleh karena itulah pada kesempatan ini
peneliti ingin menyampaikan ucapan terima kasih yang tak terhingga dan
penghargaan yang setinggi-tingginya kepada semua pihak yang telah membantu
dalam penulisan tugas akhir ini:
1. Allah SWT, Berkat rahmat dan petunjuk-Nya sehingga penulis dapat
menyelesaikan tugas akhir ini.
2. dr. Irma Suswati, M.Kes., selaku Dekan Fakultas Kedokteran Universitas
Muhammadiyah Malang atas bimbingannya selama di FK UMM.
3. dr. Meddy Setiawan, Sp.PD., selaku dosen pembimbing I yang telah
meluangkan waktu dan penuh kesabaran berkenan membimbing serta
mengarahkan penulis dalam menyelesaikan tugas akhir ini.
vi
4. dr. Nuryati, selaku dosen pembimbing II yang penuh kesabaran berkenan
meluangkan waktu serta penuh kesabaran untuk membimbing, mengarahkan,
dan memberi masukan dalam menyelesaikan tugas akhir ini.
5. dr. Mochammad Ma’roef, Sp.OG, selaku dosen penguji dan dosen
pembimbing akademik yang telah membantu dan memberi masukan dan
bimbingan yang sangat membantu penulis dalam penyelesaian tugas akhir ini.
6. Bapak Dr. Yusuf, MP selaku peneliti ubijalar ungu Klon MSU 03028-10
(Varietas Antin-3), yang bersedia memberikan sampel ubijalar ungu serta
membimbing penulis tentang deskripsi tanaman ubijalar ungu dengan baik.
7. Dr. H. M. Ramli, MA., dan Hj. Siti Nafi’ah, S.Pd., selaku orang tua penulis
yang telah bekerja keras untuk memberikan semua yang terbaik, dan selalu
memberikan doa, mengarahkan, membimbing, serta memberikan semangat
kepada penulis sehingga bisa menyelesaikan tugas akhir ini.
8. Fata Nugraha dan Raihan Akbar selaku adik-adik penulis, terima kasih atas
doa, semangat, saran, dan idenya dalam membantu kelancaran tugas akhir ini.
9. Tatok Hadi Kuswoyo, S.Ked., selaku kakak dan sahabat yang selalu
memberikan inspirasi, terima kasih atas doa, semangat, dan arahannya dalam
membantu kelancaran tugas akhir ini.
10. Devi Dewanti, Tantia Devi Iralawati, Adelia Pratiwi, Mirna Zulfa Arfiani, dan
Wien Hesthi Rahayu selaku sahabat terbaik dan orang terdekat yang selalu
setia menemani, memberi semangat, dan membantu memperbaiki kekurangan
dalam setiap proses pengerjaan tugas akhir ini.
vii
11. Pak Djoko, Mas Miftah, Pak Kus, Mas Nyono, Mbak Fat, serta semua laboran
FK UMM yang telah membantu dan membimbing melakukan tugas akhir ini
dengan penuh kesabaran.
12. Pak Yono, Bu Endah, Mas Didit dan Mas Faisal, selaku pegawai TU FK
UMM yang telah membantu dalam setiap proses demi kelancaran pengerjaan
tugas akhir ini.
13. Semua kontributor dan teman-teman lain yang tidak bisa penulis sebutkan satu
persatu disini.
Peneliti menyadari sepenuhnya bahwa masih banyak kekurangan pada
penyusunan tugas akhir ini. sehingga peneliti sangat mengharapkan masukan dari
berbagai pihak. Semoga tugas akhir ini dapat memberikan manfaat bagi penulis
dan pembaca, menjadi sumbangan yang berguna bagi perkembangan ilmu
pengetahuan serta dapat bermanfaat bagi semua pihak.
Malang, Agustus 2014
Penulis
viii
ABSTRAK
Nabila, Farahiya. 2014. Pengaruh Ekstrak Ubijalar Ungu (Ipomoea batatas)
Varietas Antin-3 Terhadap Penurunan Kadar Malondialdehida (MDA)
Hepar Tikus Putih Jantan (Rattus novergicus) Strain Wistar yang
Diinduksi Isoniazid dan Rifampisin. Karya Tulis Akhir, Fakultas
Kedokteran, Universitas Muhammadiyah Malang. Pembimbing: (1)
Meddy Setiawan* (2) Nuryati**
Latar Belakang: Terpaparnya hepar oleh berbagai senyawa menjadikan
probabilitas hepatotoksik semakin meningkat. Berbagai macam obat diketahui
dapat mengakibatkan hepatotoksisitas, salah satunya obat anti tuberkulosis yaitu
INH dan RIF. Ubijalar ungu varietas Antin-3 diduga mengandung banyak
antosianin yang dapat bersifat sebagai hepatoprotektif.
Tujuan Penelitian: Membuktikan pengaruh ekstrak ubijalar ungu varietas Antin-
3 terhadap penurunan kadar MDA hepar tikus putih jantan strain wistar yang
diinduksi INH dan RIF.
Metode Penelitian: The Post Test Only Control Group Design yang terbagi
dalam lima kelompok secara acak, masing-masing terdapat 6 hewan coba, dan
dilakukan selama 28 hari sebagai berikut. Kelompok I tanpa perlakuan, kelompok
II diberi INH dan RIF masing-masing 200 mg/kg bb/hari. Tiga kelompok lain (III,
IV, dan V) diberi INH dan RIF masing-masing 200 mg/kg bb/hari serta ekstrak
ubijalar ungu varietas Antin-3 dosis 200, 400, dan 800 mg/kg bb/hari. Analisis
data menggunakan One Way ANOVA, uji LSD, uji korelasi, dan uji regresi linier.
Hasil Penelitian: Uji One Way ANOVA didapatkan nilai Sig (2-tailed) = 0,000 (p
< 0,05), terdapat pengaruh bermakna pada pemberian ekstrak ubijalar ungu
varietas Antin-3 terhadap penurunan kadar MDA hepar. Uji korelasi didapatkan
Sig (2-tailed) = 0,000 (p < 0,05) dan Pearson Correlation = -0,825, terdapat
korelasi yang berbanding terbalik dan sangat kuat antara dosis pemberian ekstrak
ubijalar ungu varietas Antin-3 dan penurunan kadar MDA hepar. Uji regresi linier
didapatkan nilai R2 = 0,681, penurunan kadar MDA hepar dipengaruhi oleh dosis
pemberian ekstrak ubijalar ungu varietas Antin-3 sebesar 68,1%.
Kesimpulan: Ekstrak ubijalar ungu varietas Antin-3 dapat menurunkan kadar
MDA hepar tikus yang diinduksi INH dan RIF.
Kata Kunci: ekstrak ubijalar ungu varietas Antin-3, INH, RIF, kadar MDA hepar
*Staf Pengajar FK UMM, Spesialis Penyakit Dalam.
**Staf Pengajar FK UMM
ix
ABSTRACT
Nabila, Farahiya. 2014. The Influence of Extract Purple Sweet Potato (Ipomoea
batatas) Variety Antin-3 Toward Liver Decrease Levels of
Malondialdehyde (MDA) in White-Male Albino Rats (Rattus novergicus)
Strain Wistar that Induced by Isoniazid and Rifampicin. Final
Assignment, Medical Faculty, University of Muhammadiyah Malang.
Advisors: (1) Meddy Setiawan* (2) Nuryati**
Background: The liver exposure by various compounds can increase the
probability of hepatotoxicity itself. One of them is antitubercular drugs, such as
INH and RIF. Purple sweet potato variety Antin-3 expected contain much
anthocyanin that have hepatoprotective effect.
Objective: This research was aimed to determine the influence of extract purple
sweet potato (Ipomoea batatas) variety Antin-3 toward liver decrease levels of
MDA in white-male albino rats (Rattus novergicus) strain wistar that induced by
INH and RIF.
Methods: The Post Test Only Control Group Design, were randomly divided into
five groups, each group containg 6 animals and treated for 28 days, as follows.
Group I was negative control, group II was induced INH and RIF each 200 mg/kg
bw/day. The other three groups (III, IV, and V) were induced INH and RIF each
200 mg/kg bw/day together with extract purple sweet potato (Ipomoea batatas)
variety Antin-3 doses 200, 400, and 800 mg/kg bw/day. The data was analized by
One Way ANOVA, LSD, correlation, and linear regression tests.
Results: One Way ANOVA test revealed of value Sig (2-tailed) = 0.000 (p < 0,05),
there were a significant influence of the extract purple sweet potato (Ipomoea
batatas) variety Antin-3 toward liver decrease levels of MDA. The correlation test
revealed Sig (2-tailed) = 0.000 (p < 0,05) with the value of Pearson Correlation =
-0,825, there were an obviously and strongly correlation between the extract
purple sweet potato (Ipomoea batatas) variety Antin-3 doses and liver decrease
levels of MDA. In regression test result was R2 = 0,681, which meant that liver
decrease levels of MDA can be affected by the extract purple sweet potato
(Ipomoea batatas) variety Antin-3 doses in 68,1%.
Conclusion: The extract purple sweet potato (Ipomoea batatas) variety Antin-3
can reduce liver decrease levels of MDA in white-male albino rats (Rattus
novergicus) strain wistar that induced by INH and RIF.
Keywords: Extract purple sweet potato variety Antin-3, INH, RIF, liver decrease
levels of MDA
* Lecturer of FK UMM, Internist.
**Lecturer of FK UMM
x
DAFTAR ISI
Halaman
HALAMAN JUDUL ............................................................................................... i
LEMBAR PENGESAHAN LAPORAN HASIL PENELITIAN .......................... iii
KATA PENGANTAR ............................................................................................ v
ABSTRAK ........................................................................................................... viii
ABSTRACT ........................................................................................................... ix
DAFTAR ISI .......................................................................................................... x
DAFTAR GAMBAR .......................................................................................... xiii
DAFTAR TABEL ............................................................................................... xiv
DAFTAR SINGKATAN ..................................................................................... xv
DAFTAR LAMPIRAN ...................................................................................... xvii
BAB 1 PENDAHULUAN ...................................................................................... 1
1.1 Latar Belakang ........................................................................................ 1
1.2 Rumusan Masalah................................................................................... 3
1.3 Tujuan Penelitian .................................................................................... 4
1.3.1 Tujuan Umum ............................................................................... 4
1.3.2 Tujuan Khusus .............................................................................. 4
1.4 Manfaat Penelitian ................................................................................... 4
1.4.1 Klinis ............................................................................................. 4
1.4.2 Akademis ...................................................................................... 4
1.4.2 Masyarakat .................................................................................... 4
BAB 2 TINJAUAN PUSTAKA ............................................................................. 5
2.1 Ubijalar Ungu .......................................................................................... 5
2.1.1 Taksonomi Ubijalar Ungu ............................................................. 5
2.1.2 Morfologi Ubijalar Ungu .............................................................. 5
2.1.3 Varietas Ubijalar Ungu ................................................................. 6
2.1.4 Kandungan Antosianin pada Ubijalar Ungu ................................. 7
2.1.5 Potensi Antosianin pada Ubijalar Ungu ...................................... 10
2.2 Hepar .................................................................................................... 15
2.2.1 Anatomi Hepar ............................................................................ 15
xi
2.2.2 Histologi Hepar ........................................................................... 16
2.2.3 Fisiologi Hepar ............................................................................ 18
2.2.4 Proses Biotransformasi Obat di Hepar ........................................ 18
2.3 Isoniazid (INH) dan Rifampisin (RIF) ................................................. 20
2.3.1 Isoniazid (INH) ........................................................................... 20
2.3.2 Rifampisin (RIF) ......................................................................... 22
2.4 Mekanisme Hepatotoksisitas INH dan RIF ......................................... 23
2.5 Radikal Bebas, Stres Oksidatif, dan Malondialdehida (MDA) ............ 28
2.5.1 Radikal Bebas dan Stres Oksidatif .............................................. 28
2.5.2 Malondialdehida (MDA) ............................................................. 30
BAB 3 KERANGKA KONSEP DAN HIPOTESIS PENELITIAN .................... 34
3.1 Kerangka Konsep ................................................................................. 34
3.2 Hipotesis Penelitian .............................................................................. 37
BAB 4 METODE PENELITIAN.......................................................................... 38
4.1 Jenis Penelitian ..................................................................................... 38
4.2 Lokasi dan Waktu Penelitian ................................................................ 38
4.3 Populasi dan Sampel Penelitian ............................................................ 38
4.3.1 Populasi Penelitian ................................................................... 38
4.3.2 Sampel Penelitian .................................................................... 38
4.3.3 Besar Sampel Penelitian .......................................................... 38
4.3.4 Teknik Pengambilan Sampel Penelitian .................................. 39
4.3.5 Karakteristik Sampel Penelitian ............................................... 39
4.3.5.1 Kriteria Inklusi ............................................................ 39
4.3.5.2 Kriteria Eksklusi .......................................................... 40
4.3.5.3 Kriteria Drop Out ........................................................ 40
4.3.6 Variabel Penelitian ................................................................... 40
4.3.6.1 Variabel Bebas ............................................................ 40
4.3.6.2 Variabel Tergantung .................................................... 40
4.3.7 Definisi Operasional Variabel Penelitian ................................ 40
4.4 Alat dan Bahan Penelitian .................................................................... 41
4.4.1 Alat ........................................................................................... 41
4.4.2 Bahan ....................................................................................... 42
xii
4.5 Alur Penelitian ...................................................................................... 43
4.6 Prosedur Penelitian ............................................................................... 43
4.6.1 Pembagian Kelompok Hewan Coba ........................................ 43
4.6.2 Adaptasi Sampel Penelitian ..................................................... 44
4.6.3 Penentuan Dosis ....................................................................... 44
4.6.3.1 Ekstrak Ubijalar Ungu ................................................ 44
4.6.3.2 Dosis INH dan RIF ...................................................... 45
4.6.4 Ekstraksi Ubijalar Ungu Varietas Antin-3 ............................... 45
4.6.5 Preparansi Sampel dan Prosedur Pengukuran MDA Hepar ... 46
4.6.5.1 Preparansi Sampel ..................................................... 46
4.6.5.2 Prosedur Pengukuran MDA Hepar ............................ 47
4.7 Analisis Data......................................................................................... 48
BAB 5 HASIL DAN ANALISIS DATA PENELITIAN ..................................... 49
5.1 Hasil Penelitian ..................................................................................... 49
5.2 Analisis Data Penelitian ........................................................................ 51
5.2.1 Analisis Normalitas dan Homogenitas ................................... 51
5.2.2 Analisis One Way ANOVA ...................................................... 51
5.2.3 Analisis Post Hoc .................................................................... 52
5.2.4 Analisis Uji Korelasi ................................................................ 53
5.2.5 Analisis Uji Regresi Linier ..................................................... 53
BAB 6 PEMBAHASAN ....................................................................................... 55
BAB 7 KESIMPULAN DAN SARAN ................................................................ 60
7.1 Kesimpulan ........................................................................................... 60
7.2 Saran ..................................................................................................... 60
DAFTAR PUSTAKA ........................................................................................... 62
LAMPIRAN .......................................................................................................... 67
xiii
DAFTAR GAMBAR
Halaman
Gambar 2.1 Ubijalar Ungu (Ipomoea batatas) ....................................................... 5
Gambar 2.2 Rumus Bangun Kimia Antosianin ...................................................... 8
Gambar 2.3 Rumus Bangun Kimia Antosianidin ................................................... 9
Gambar 2.4 Mekanisme Pengikatan ONOO- oleh Pelagornidin ........................... 11
Gambar 2.5 Mekanisme Antioxidant Response Element (ARE) ........................... 12
Gambar 2.6 Pencegahan Formasi Radikal Bebas Metal-Induced ......................... 13
Gambar 2.7 Posisi Hepar di Abdomen .................................................................. 15
Gambar 2.8 Struktur Makroskopik Hepar Anterior dan Posterior ........................ 16
Gambar 2.9 Struktur Mikroskopik Hepar ............................................................. 17
Gambar 2.10 Rumus Bangun Kimia INH ............................................................. 20
Gambar 2.11 Mekanisme Metabolisme INH ........................................................ 21
Gambar 2.12 Rumus Bangun Kimia RIF .............................................................. 22
Gambar 2.13 Mekanisme INH yang Menginduksi Kerusakan Hepar .................. 24
Gambar 2.14 Kerusakan Sel .................................................................................. 25
Gambar 2.15 Mekanisme Kerusakan Hepar ......................................................... 26
Gambar 2.16 Kondisi Hepatosit Akibat Kerusakan Mitokondria ......................... 27
Gambar 2.17 Mekanisme RIF yang Menginduksi Kerusakan Hepar ................... 28
Gambar 2.18 Hasil dari Stres Oksidatif ................................................................ 29
Gambar 2.19 Rumus Bangun Kimia MDA ........................................................... 30
Gambar 2.20 Tiga Fase Pembentukan LPO .......................................................... 30
Gambar 2.21 Hasil dari Tiga Fase Pembentukan LPO ......................................... 32
Gambar 3.1 Kerangka Konsep .............................................................................. 34
Gambar 4.1 Alur Penelitian................................................................................... 43
Gambar 4.2 Pembedahan Tikus ............................................................................ 47
Gambar 5.1 Grafik Rata-rata Kadar MDA (ng/ml) ............................................... 49
Gambar 5.2 Grafik Regresi Kadar MDA (ng/ml) ................................................. 54
xiv
DAFTAR TABEL
Halaman
Tabel 2.1 Nilai Gizi Ubijalar Ungu (Ipomoea batatas) .......................................... 6
Tabel 4.1 Pembagian Kelompok Hewan Coba ..................................................... 44
Tabel 5.1 Hasil Pengukuran Kadar MDA (ng/ml) ................................................ 49
Tabel 5.2 Resume Tabel Uji Analisis Post Hoc: LSD .......................................... 52
xv
DAFTAR SINGKATAN
AP-1 : Activator Protein 1
ARE : Antioxidant Response Element
ATP : Adenosine-5’-triphosphate
C/EBP : CCAAT/Enhancer-Binding Protein
Ca : Calcium
CAT : Catalase
COX : Cyclooxygenase
COX-1 : Cyclooxygenase-1
COX-2 : Cyclooxygenase-2
CREB : CRE-binding protein
CYP : Cytochrome
CYP1A2 : Cytochrome 1A2
CYP2E1 : Cytochrome 2E1
CYP450 : Cytochrome P-450
DNA : Deoxyribonucleic Acid
EBP : Enhancer-Binding Protein
Fe : Ferrum
GPX : Glutathione Peroxidase
GR : Glutathione Reductase
GSH : Glutathione
GSSG : Glutathione Disulfide
GST : Glutathione S-Transferase
HNE : Hydroxynonenal
HOCl : Hypochlorous Acid
HPLC : High Performance Liquid Chromatography
H2O2 : Hydrogen Peroxide
INH : Isoniazid
K : Kalium
KLT : Kromatografi Lapis Tipis
LPO : Lipid Peroxidation
MAPK : Mitogen-Activated Protein Kinase
MDA : Malondialdehyde
MFO : Mixed-Function Oksidase
Mg : Magnesium
Mn : Mangan
MOMP : Mitochondrial Outer Membrane Permeabilisation
mPT : mitochondrial Permeability Transition
mPTPs : mitochondrial Permeability Transition Pores
MT : Metil Transferase
mtDNA : mitochondrial Deoxyribonucleic Acid
Na : Natrium
NADPH : Nikotinamide Adenine Dinukleotide Phosphate Oxidase
NAT : N-Asetil Transferase
NAT-1 : N- Asetil Transferase 1
NAT-2 : N- Asetil Transferase 2
xvi
NF-κB : Nuclear Factor-kappa B
NO : Nitrite Oxide
OAT : Obat Anti Tuberkulosis
OH : Hydroxyl
OH. : Hydroxyl Radical
ONOO-
: Peroxinitrite
O2.-
: Radical Superoxide
‘O2 : Singlet Oxygen
PARP : Poly-ADP Ribose Polymerase
pH : The Power of Hydrogen
PUFA : Poly Unsaturated Fatty Acid
PXR : Preganane X Receptor
RIF : Rifampisin
RNS : Reactive Nitrogen Species
ROO− : Peroxide
ROS : Reactive Oxygen Species
rRNA : ribosomal Ribonucleic Acid
RXR : Retinoid X Receptor
S : Sulphur
SOD : Superoxida Dismutase
SULT : Sulfotransferase
TB : Tuberculosis
TBARS : Thiobarbituric Acid Reactive Substance
UGT : UDP-Glukuronil-Transferase
xvii
DAFTAR LAMPIRAN
Halaman
Lampiran 1. Hasil Pengukuran MDA ................................................................... 67
Lampiran 2. Hasil Analisis Data Penelitian .......................................................... 69
Lampiran 3. Dokumentasi Penelitian .................................................................... 72
Lampiran 4. Kartu Konsultasi Pembimbing I ....................................................... 77
Lampiran 5. Kartu Konsultasi Pembimbing II ...................................................... 78
Lampiran 6. Surat Keterangan Laboratorium Biomedik FK UMM ..................... 79
Lampiran 7. Surat Keterangan UPT Balai Konservasi Tumbuhan ....................... 80
Lampiran 8. Surat Keterangan Keputusan Menteri Pertanian RI ......................... 81
Lampiran 9. Deskripsi Ubijalar Varietas Antin-3 ................................................. 83
62
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