i

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

DAFTAR PUSTAKA

Aishah B, Nursabrina M, Noriham A, et al 2013, Anthocyanins from Hibiscus

sabdariffa, Melastoma malabathricum and Ipomoea batatas and Its Color

Properties, International Food Research Journal, vol.20(2), pp.827-834.

Ali ZY, 2012, Biochemical Evaluation of Some Natural Products Against

Toxicity Induced by Anti-Tubercular Drugs in Rats, New York Science

Journal, vol.5(10), pp. 69-80.

Andrawulan N, Fadilla FRH, 2012, Merah-Ungu Antosianin, In: Pewarna Alami

untuk Pangan, South East Asian Food and Agricultural Science and

Technology (SEAFAST) Center, Institut Pertanian Bogor, Bogor-

Indonesia, hal.23-29.

Basini J, Mohanalakshmi S, Anitha K, 2013, Antihepatotoxic Effect of Barleria

montana Leaves Against Anti-TB Drugs Induced Hepatotoxicity,

International Research Journal of Pharmacy, vol.4(6), pp.97-101.

Balitkabi, 2013, ANTIN-2 dan ANTIN-3, Generasi Baru Ubi Jalar Ungu, viewed

18 January 2014, <http://pangan.litbang.deptan.go.id/berita-103-antin-2-

dan-antin-3-generasi-baru-ubi-jalar-ungu.html>.

CCRC Farmasi UGM, 2014, Cancer Chemoprevention Research Center Fakultas

Farmasi UGM: Prosedur Tetap Pembedahan Hewan Uji, viewed 6 January

2014, <http://ccrc.farmasi.ugm.ac.id/wp-content/uploads/sop-bedah-tikus.

p >.

Chambers HF, 2007, Antimycobacterium Drugs, in Katzung BG (ed.), Basic and

Clinical Pharmacology, 10th

edn, McGraw-Hill, London-United Kingdom,

pp.771-780.

Dahlan MS, 2012, Statistik untuk Kedokteran dan Kesehatan: Deskriptif, Bivariat,

dan Multivariat dilengkapi Aplikasi dengan Menggunakan SPSS, Edisi 5,

Salemba Medika, Jakarta-Indonesia, hal.87-231.

Dai J, Mumper RJ, 2010, Plant Phenolics: Extraction, Analysis and Their

Antioxidant and Anticancer Properties, Molecules, pp.7313-7352, viewed

10 January 2014, <http://www.mdpi.com/journal/molecules>.

Eroschenko VP, 2010, Sistem Pencernaan: Hepar, Kandung Empedu, dan

Pankreas, In: Atlas Histologi Di Fiore dengan Korelasi Fungsional, Edisi

11, Penerbit Buku Kedokteran EGC, Jakarta-Indonesia, hal.215-223.

Ginting E, Utomo JS, Yulifianti R, dkk, 2011, Potensi Ubi Jalar Ungu sebagai

Pangan Fungsional, IPTEK Tanaman Pangan, vol.6, no.1, hal.116-138.

63

Goodman, Gilman, 2007, Dasar Farmakologi Terapi, Edisi 10, Penerbit Buku

Kedokteran EGC, Jakarta-Indonesia, hal.201-222.

Grattagliano I, Bonfrate L, Diogo CV, et al, 2009, Biochemical Mechanisms in

Drug-Induced Liver Injury: Certainties and Doubts, World Journal of

Gastroenterology, vol.15(39), pp.4865-4876.

Gray H, Drake R, Vogl W, et al, 2010, Gray's Anatomy for Students,

Elsevier/Churchill Livingstone, Philadelphia-United States of America,

pp.226-230.

Guyton AC, Hall JE, 2008, Liver as An Organ, Textbook of Medical Physiology,

11th

edn, Elsevier, Singapore, pp.902-908.

Hussain T, Gupta RK, Sweety K, et al, 2012, Evaluation of Antihepatotoxic

Potential of Solanum xanthocarpum Fruit Extract Against Antitubercular

Drugs Induced Hepatopathy In Experimental Rodents, Asian Pacific

Journal of Tropical Biomedicine, vol.2(6), pp.454-460.

Istiantoro YH, Setiabudy R, 2009, Tuberkulostatik dan Leprostatik, In: Gunawan

SG, Setiabudy R, Nafriadi, dkk (eds.), Farmakologi dan Terapi FK UI,

Edisi 5, Balai Penerbit Fakultas Kedokteran Universitas Indonesia,

Jakarta-Indonesia, hal.613-617.

Jawi IM, Budiasa K, 2011, Ekstrak Air Umbi Ubi Jalar Ungu Menurunkan Total

Kolesterol serta Meningkatkan Total Antioksidan Darah Kelinci, Jurnal

Veteriner, vol.12, no.2, hal.120-125.

Jehangir A, Nagi AH, Shahzad M, et al, 2010, The Hepato-Protective Effect of

Cassia fistula (Amaltas) Leaves in Isoniazid and Rifampicin Induced

Hepatotoxicity in Rodents, Biomedica, vol.26, pp.25-29.

Jiao Y, Jiang Y, Zhai W, et al, 2012, Studies on Antioxidant Capacity of

Anthocyanin Extract From Purple Sweet Potato (Ipomoea batatas L.),

African Journal of Biotechnology, vol.11(27), pp.7046-7054.

Jusuf M, Rahayuningsih SA, Ginting E, 2008, Ubi Jalar Ungu, Warta Penelitian

dan Pengembangan Pertanian, vol.30, no.4, pp.13-14.

Kementrian Kesehatan RI, 2013, Pedoman Nasional Pelayanan Kedokteran: Tata

Laksana Tuberkulosis, Kementrian Kesehatan RI, viewed 6 January 2014,

<http://kncv.or.id/images/xplod/publication/pedomannasionaltuberkulosa.

pdf>.

Kumar GS, Krishna BRB, Kumar GV, et al, 2010, Hepatoprotective and

Antioxidant Activity of The Alcoholic Extract of Ipomoea turpetnm

Against Anti-TB Drugs Induced Hepatotoxicity in Rats, Journal of

Advances in Drug Research, vol.1, no.1, pp.10-19.

64

Lazuardi RNM, 2010, Mempelajari Ekstraksi Pigmen Antosianin dari Kulit

Manggis (Garcinia mangostana L.) dengan Berbagai Jenis Pelarut,

Skripsi, Fakultas Teknik Jurusan Teknologi Pangan, Universitas Pasundan,

Bandung-Indonesia, hal.12-14.

Li T, Chiang JYL, 2006, Rifampicin Induction of CYP3A4 Requires Pregnane X

Receptor Cross Talk with Hepatocyte Nuclear Factor 4 and Coactivators,

and Suppression of Small Heterodimer Partner Gene Expression, Drug

Metabolism and Disposition, vol.34, pp.756-764.

Lima MFS, Melo HRL, 2012, Hepatotoxicity Induce by Antituberculosis Drugs

among Patients Coinfected with HIV and Tuberculosis, Cad Saude

Publica, vol.28(4), pp.698-708.

Ma X, Idle JR, Gonzales FJ, 2008, The Pregnane X Receptor: From Bench to

Bedside, Expert Opin Drug Metabolisme of Toxicology, vol.4(7), pp.895-

908.

Melawaty L, 2010, Ekstraksi Pigmen Antosianin Paprika Merah (Capsicum

anuum) dengan Menggunakan Asam Tartarat, Indonesian Scientific

Journal Database, vol.4(2), hal.7-11.

Miguel MG, 2011, Anthocyanins: Antioxidant and/or Anti-Inflammatory

Activities, Journal of Pharmaceutical Science, vol.1(6), pp.7-15.

Montilla EC, Hillebrand S, Winterhalter P, 2011, Anthocyanins in Purple Sweet

Potato (Ipomoea batatas L.) Varieties, Fruit, Vegetable, and Cereal

Science and Biotechnology, vol.5(2), pp.19-24.

Porceddu M, Buron N, Roussel C, et al, 2012, Prediction of Liver Injury Induced

by Chemicals in Human with a Multiparametric Assay on Isolated Mouse

Liver Mitochondria, Toxicological Sciences, vol.129(2), pp.332–345.

Putz R, Pabst R, 2007, Atlas Anatomi Manusia Sobotta Jilid 2: Batang Badan,

Panggul, Ekstremitas Bawah, Edisi 22, Penerbit Buku Kedokteran EGC,

Jakarta-Indonesia, hal.142-143.

Richanna N, 2013, Menggali Potensi Ubi Kayu dan Ubu Jalar, Penerbit Nuansa

Cendikia, Bandung-Indonesia, hal.9-28.

Setiawan B, Suhartono E, 2007, Peroksidasi Lipid dan Penyakit Terkait Stres

Oksidatif pada Bayi Prematur, Majalah Kedokteran Indonesia, vol.57,

no.1, hal.10-14.

Setiawati A, Suyatna FD, Gan S, 2009, Pengantar Farmakologi, In: Gunawan SG,

Setiabudy R, Nafriadi, dkk (eds.), Farmakologi dan Terapi FK UI, Edisi 5,

65

Balai Penerbit Fakultas Kedokteran Universitas Indonesia, Jakarta-

Indonesia, hal.8-10.

Siswonoto S, 2008, Hubungan Kadar Malondialdehid Plasma dengan Keluaran

Klinis Stroke Iskemik Akut, Thesis, Program Pasca Sarjana Magister Ilmu

Biomedik dan PPDS Ilmu Penyakit Saraf, Universitas Diponegoro,

Semarang-Indonesia.

Soemardhini, Kapti RE, Trishinta SM, 2012, Pengaruh Pemberian Bentonite

Terhadap Penurunan Kadar Malondialdehyde (MDA) Jaringan Hepar

Rattus novergicus yang Dipapar Herbisida Paraquat, Artikel Tugas Akhir

FKUB, viewed 22 December 2013, <http://old.fk.ub.ac.id/artikel/id/

kedokteran.php?module=home>.

Soewandhi SN, Kosasih, Mauludin R, dkk, 2007, Pengaruh Energi Mekanik dan

Termik Terhadap Senyawa Rifampisin, Majalah Farmasi Indonesia,

vol.18(3), hal.124–132.

Stirnimann G, Kessebohm K, Lauterburg B, 2010, Liver Injury Caused by Drugs:

An Update, Swiss Medical Weekly, The European Journal of Medical

Science, vol.140, viewed 22 December 2013,

<http://www.uptodate.com/contents/drugs-and-the-liver-pattern-of-drug-

induced-liver-injury/abstracts/23>.

Suarsana IN, Utama IH, Agung IG, dkk, 2011, Pengaruh Hiperglikemia dan

Vitamin E pada Kadar Malondialdehida dan Enzim Antioksidan Intrasel

Jaringan Pankreas Tikus, MKB, vol.43, no.2, hal.72-76.

Supranto J, 2007, Teknik Sampling Untuk Survei dan Eksperimen, PT Rineka

Cipta, Jakarta.

Syamsudin, Darmono, 2011, Farmakologi Eksperimental, Penerbit Universitas

Indonesia (UI-Press), Jakarta-Indonesia, hal.7-11.

Tayal V, Kalra BS, Agarwal S, et al, 2007, Hepatoprotective Effect of Tocopherol

Against Isoniazid and Rifampicin Induced Hepatotoxicity in Albino

Rabbits, Indian Journal of Experimental Biology, vol.45, pp.1031-1036.

Texeira RLDF, Morato RG, Cabello PH, et al, 2011, Genetic Polymorphisms or

NAT2, CYP2E1, and GST Enzymes and The Occurrence of

Antituberculosis Drug-induced Hepatitis in Brazilian TB Patients, Mem

Inst Oswldo Cruz, vol.106, no.6, pp.716-724.

UFAW, 2006, The UFAW Handbook on The Care and Management of

Laboratorium Animals, 5th

edn, Edinburgh Churchil Livingstone, pp.257-

302.

66

Wang LS, Stoner GD, 2008, Anthocyanins and Their Role In Cancer Prevention,

Cancer Lett, vol.269(2), pp.281–290.

World Health Organization, 2013, Global Tuberculosis Report 2013, viewed 6

January 2014, <apps.who.int/iris/bitstream/10665/91355/1/978924156465

6_eng.pdf>.

Yustika AR, Aulanni’am, Prasetyawan S, 2013, Ka ar Malon ial ehi (MDA)

dan Gambaran Histologi pada Ginjal Tikus Putih (Rattus novergicus)

Pasca Induksi Cylosprine-A, Kimia Student Journal, vol.1, no.2, hal.222-

228.

Zainuri M, Wanandi SI, 2012, Aktivitas Spesifik Manganese Superoxide

Dismutase (MnSOD) dan Katalase Pada Hati Tikus yang Diinduksi

Hipoksia Sistemik: Hubungannya Dengan Kerusakan Oksidatif, Media

Litbang Kesehatan, vol.22, no.2, hal.87-92.

Zhao CL, Guo HC, Dong ZY, et al, 2009, Pharmacological and Nutritional

Activities of Potato Anthocyanins, African Journal of Pharmacy and

Pharmacology, vol.2(10), pp.463-468.

Zozio S, Pallet D, Dornier M, 2011, Evaluation of Anthocyanin Stability During

Storage of Coloured Drink Made from Extracts of The Andean Blackberry

(Rubus glaucus Benth.), Acai (Euterpe oloracea Mart.) and Black Carrot

(Daucus carota L.), Fruits, vol.66, pp.203-215.