KARYA TULIS AKHIR EFEK HEPATOPROTEKTIF EKSTRAK BIJI ANGGUR MERAH (Vitis vinifera L.) TERHADAP KADAR SGOT DAN SGPT PADA TIKUS PUTIH JANTAN (Rattus norvegicus strain wistar) YANG DIINDUKSI ALKOHOL SUBAKUT
Oleh : LINDA DWI SWASTIKA 201110330311090
UNIVERSITAS MUHAMMADIYAH MALANG FAKULTAS KEDOKTERAN 2015
KARYA TULIS AKHIR
EFEK HEPATOPROTEKTIF EKSTRAK BIJI ANGGUR MERAH (Vitis vinifera L.) TERHADAP KADAR SGOT DAN SGPT PADA TIKUS PUTIH JANTAN (Rattus norvegicus strain wistar) YANG DIINDUKSI ALKOHOL SUBAKUT
Diajukan kepada Universitas Muhammadiyah Malang Untuk Memenuhi Salah Satu Persyaratan Dalam Menyelesaikan Program Sarjana Fakultas Kedokteran
Oleh : LINDA DWI SWASTIKA 201110330311090
UNIVERSITAS MUHAMMADIYAH MALANG FAKULTAS KEDOKTERRAN 2015
KATA PENGANTAR
Assalamu’alaikum Wr. Wb. Puji syukur kehadirat Allah SWT Yang Maha Pengasih lagi Maha Penyayang, Yang Maha Pemberi semua nikmat, kebaikan, dan kekuatan selama proses pelaksanaan, Yang Maha Menyimpan rahasia hikmah di balik semua peristiwa, Yang Maha Memudahkan, dan atas karunia-Nya, penulisan tugas akhir ini dapat selesai dengan baik. Shalawat serta salam selalu tercurahkan kepada Rasulullah Muhammad shalallahu alaihi wasallam, keluarganya dan para sahabatnya yang telah berjasa membawa syiar dakwah Islam ke seluruh dunia. Penelitian tugas akhir ini berjudul “Efek Hepatoprotektif Ekstrak Biji Anggur Merah (Vitis vinifera L.) Terhadap Kadar SGOT dan SGPT Pada Tikus Putih Jantan (Rattus norvegicus strain wistar) yang Diinduksi Alkohol Subakut”. Tugas akhir ini diajukan untuk memenuhi persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas Muhammadiyah Malang. Pada kesempatan ini, penulis ingin menyampaikan terimakasih kepada : 1.
dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran Universitas Muhammadiyah Malang atas ilmu dan bimbingannya selama di Fakultas Kedokteran UMM.
2.
dr. Moch. Ma’roef, SpOG, selaku Pembantu Dekan I Fakultas Kedokteran UMM atas kesediaan waktu dan penyampaian ilmu yang sangat bermanfaat bagi masa depan para mahasiswa FK UMM.
iv
3.
dr. Rahayu, SpS, selaku Pembantu dekan II Fakultas Kedokteran UMM yang senantiasa bersabar dalam membimbing dan mengajarkan ilmunya kepada kami.
4.
dr. Iwan Sys Indrawanto, SpKJ selaku Pembantu Dekan III, yang penuh semangat dalam menyampaikan ilmu dan motivasi yang membangun semangat kami selama menjalani pendidikan di Fakultas Kedokteran.
5.
Prof. Dr. dr. Djoni Djunaedi, SpPD, KPTI, selaku pembimbing 1, atas kesabaran, kebaikan hati, serta kesediaan dalam meluangkan waktu dalam membimbing hingga dapat menyelesaikan penelitian ini dengan baik.
6.
dr. Fathiyah Safithri, M.Kes, selaku pembimbing 2, atas kesabaran, kebaikan
hati,
serta
kesediaan
dalam
meluangkan
waktu
dalam
membimbing penulis hingga dapat menyelesaikan penelitian ini dengan baik. 7.
dr. Bambang Widianto, SpOT, selaku penguji tugas akhir ini, atas segala masukan dan arahan yang sangat bermanfaat dalam pengerjaan tugas akhir ini dan kesediaan waktu, sehingga tugas ini dapat diselesaikan dengan baik.
8.
Ibu, bapak, atas doa yang diberikan dari pagi hingga pagi lagi, serta dukungan moril dan materil yang tak pernah putus agar tugas ini dapat selesai dengan baik. Kakak Dian, terimakasih sudah menjadi kakak terbaik yang membuat penulis selalu semangat dalam menyelesaikan tugas akhir ini.
9.
Seluruh staf TU dan laboran, Mas Miftah dan Pak Joko yang bersedia membantu setiap tahapan proses penelitian hingga penyelesaian tugas akhir ini.
v
10.
Sejawat FK UMM angkatan 2011, Adorables, atas dukungan, bantuan, dan kerjasamanya. Semoga kelak dapat menjadi dokter-dokter profesional yang barokah, sukses dunia akhirat, dan senantiasa dalam ketaatan kepada Allah SWT.
11.
Kawan seperjuangan “Grup Biji Anggur Merah” Ayu Desi Prabawati dan Dea Saraswati.
12.
Sahabat-sahabat terbaik yang menjadi keluarga selama di Malang, Erfian, Tari, lili, Ani, Imaniyah, Muqsit, Fatur, Rofwiun, Putri, Laksita, Jeanny, Putrinda, Mariyah, terimakasih atas kebersamaan yang sederhana, bantuan, kesabaran, motivasi, dukungan, dan semua yang telah diberikan.
13.
Semua pihak yang terlibat secara langsung maupun tidak langsung, terimakasih atas bantuan dan dukungannya. Penulis menyadari bahwa tugas akhir ini masih jauh dari kata sempurna. Oleh karena itu, penulis sangat mengharapkan saran dan masukan yang membangun. Dengan mengharapkan Keridhaan-Nya, semoga karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi semua pihak.
Malang, 13 Agustus 2015
Penulis
vi
DAFTAR ISI JUDUL ............................................................................................................... i LEMBAR PENGESAHAN ............................................................................... ii LEMBAR PENGUJIAN .................................................................................... iii KATA PENGANTAR ....................................................................................... iv ABSTRAK ......................................................................................................... vii DAFTAR ISI ...................................................................................................... ix 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 ............................................................................. 3 1.3.1 Tujuan umum .......................................................................... 3 1.3.2 Tujuan khusus ......................................................................... 3 1.4 Manfaat Penelitian ........................................................................... 4 1.4.1 Manfaat akademi ..................................................................... 4 1.4.2 Manfaat klinis .......................................................................... 4 1.4.3 Manfaat masyarakat ................................................................ 4 BAB 2 TINJAUAN PUSTAKA ....................................................................... 5 2.1 Hati ................................................................................................... 5 2.1.1 Anatomi dan histologi hati ...................................................... 5
ix
2.1.2 Fisiologi hati .......................................................................... 8 2.1.3 Enzim hati .............................................................................. 9 2.2 Kerusakan Hati ................................................................................. 11 2.2.1 Penyebab kerusakan hati ......................................................... 11 2.2.2 Toksikologi ............................................................................. 11 2.2.3 Alkohol sebagai penyebab kerusakan hati ............................... 12 2.2.3.1 Definisi alkohol ........................................................... 12 2.2.3.2 Farmakokinetik ........................................................... 14 2.2.3.3 Regenerasi hati ............................................................ 19 2.2.3.4 Efek alkohol ke hati .................................................... 22 2.2.4 Tes faal hati ............................................................................. 23 2.3 Radikal Bebas ................................................................................... 25 2.3.1 Mekanisme pembentukan ........................................................ 26 2.3.2 Sumber radikal bebas .............................................................. 26 2.3.3 Reaksi perusakan oleh radikal bebas ...................................... 27 2.4 Antioksidan ...................................................................................... 28 2.5 Anggur Merah Sebagai Sumber Antioksidan .................................. 30 2.5.1 Taksonomi ............................................................................... 30 2.5.2 Morfologi ................................................................................ 31 2.5.3 Kandungan dan manfaat anggur merah ................................... 31 2.5.4 Proantosianidin ........................................................................ 33 BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS PENELITIAN .. 36 3.1 Kerangka Konseptual Penelitian ...................................................... 36 3.2 Hipotesis Penelitian ......................................................................... 38
x
BAB 4 METODE PENELITIAN .................................................................... 39 4.1 Jenis Penelitian ................................................................................. 39 4.2 Lokasi dan Waktu Penelitian ........................................................... 39 4.2.1 Lokasi penelitian ..................................................................... 39 4.2.2 Waktu penelitian ..................................................................... 39 4.3 Populasi dan Sampel Penelitian ....................................................... 39 4.3.1 Populasi ................................................................................... 39 4.3.2 Sampel ..................................................................................... 39 4.3.3 Estimasi besar sampel ............................................................. 39 4.3.4 Teknik pengambilan sampel ................................................... 41 4.3.5 Karateristik sampel penelitian ................................................. 41 4.3.5.1 Kriteria inklusi ............................................................ 41 4.3.5.2 Kriteria eksklusi .......................................................... 41 4.3.5.3 Kriteria drop out .......................................................... 41 4.4 Variabel Penelitian ........................................................................... 42 4.4.1 Variabel bebas ......................................................................... 42 4.4.2 Variabel tergantung ................................................................. 42 4.5 Definisi Operasional Penelitian ........................................................ 42 4.6 Alat dan Bahan Penelitian ................................................................ 43 4.6.2 Alat penelitian ......................................................................... 43 4.6.2 Bahan penelitian ....................................................................... 44 4.7 Prosedur Penelitian ........................................................................... 45 4.7.1 Pembagian kelompok tikus ...................................................... 45 4.7.2 Proses adaptasi ........................................................................ 45
xi
4.7.3 Penentuan dosis ekstrak biji anggur ........................................ 46 4.7.4 Penentuan dosis dan pengenceran alkohol .............................. 47 4.7.5 Perlakuan ................................................................................. 47 4.7.6 Tahap pengamatan .................................................................. 48 4.7.7 Penguburan tikus percobaan ................................................... 50 4.7.8 Analisis data ............................................................................ 50 4.7.9 Alur penelitian ......................................................................... 51 BAB 5 HASIL PENELITIAN DAN ANALISA DATA ................................ 52 5.1 Hasil Penelitian ................................................................................ 52 5.1.1 Hasil pengukuran kadar SGOT pada tikus putih jantan (Rattus norvegicus strain wistar) yang diinduksi dengan alkohol subakut ...................................................................... 52 5.1.2 Hasil pengukuran kadar SGPT pada tikus putih jantan (Rattus norvegicus strain wistar) yang diinduksi dengan alkohol subakut ................................................................................... 53 5.2 Analisa Data ..................................................................................... 55 5.2.1 Nilai SGOT ............................................................................. 55 5.2.2 Nilai SGPT .............................................................................. 58 BAB 6 PEMBAHASAN ................................................................................... 62 BAB 7 KESIMPULAN DAN SARAN ............................................................ 67 7.1 Kesimpulan ...................................................................................... 67 7.2 Saran ................................................................................................. 67 DAFTAR PUSTAKA ....................................................................................... 69 LAMPIRAN ...................................................................................................... 77
xii
DAFTAR GAMBAR 2.1 Gambar Hati yang Terlihat dari Depan ........................................................ 5 2.2 Histologi Hati ................................................................................................ 6 2.3 Mikroskopik Sel Hati Normal ...................................................................... 8 2.4 Gambaran Demografi Konsumsi Alkohol Global ........................................ 14 2.5 Jalur Oksidatif Metabolisme Alkohol .......................................................... 15 2.6 Metabolisme Etanol dan Kerusakan Sel Hati ............................................... 17 2.7 Pengaturan Sinyal Transduksi dan Peran Trombosit dalam Regenerasi Hati 21 2.8 Perkembangan ALD Akibat Mengkonsumsi Alkohol ................................. 23 2.9 Buah Anggur Merah ..................................................................................... 30 2.10 Klasifikasi Polifenol ................................................................................... 33 2.11 Konsentrasi Proantosianidin di Dalam Makanan ....................................... 35 3.1 Skema Kerangka Konseptual ....................................................................... 36 5.1 Grafik Perbedaan Kadar SGOT Tikus pada setiap Kelompok ..................... 53 5.2 Grafik Perbedaan Kadar SGPT Tikus pada setiap Kelompok ..................... 55 5.3 Kurva Hubungan antara Dosis Ekstrak Biji Anggur Merah terhadap Kadar Enzim SGOT ................................................................................................ 58 5.4 Kurva Hubungan antara Dosis Ekstrak Biji Anggur Merah terhadap Kadar Enzim SGPT ................................................................................................ 61
xiii
DAFTAR TABEL 2.1 Marker Biokimia akibat Hepatotoksik dalam Plasma Darah dan Serum ..... 24 2.2 Kandungan Gizi Anggur Merah atau Hijau per 100 g ................................. 32 5.1 Efek Ekstrak Biji Anggur Merah terhadap Kadar SGOT (IU/L) pada Tikus yang diinduksi Alkohol Subakut .................................................................. 52 5.2 Efek Ekstrak Biji Anggur Merah terhadap Kadar SGPT (IU/L) pada Tikus yang diinduksi Alkohol Subakut .................................................................. 54
xiv
DAFTAR SINGKATAN AcAc
:
Asam Asetoasetat
ADH
:
Alcohol Dehidrogenase
ALD
:
Alcoholic Liver Disease
ALP
:
Alkaline Phosphatase
ALT
:
Alanine Aminotransferase
AST
:
Aspartate Aminotransferase
BMI
:
Body Mass Index
CAT
:
Catalase
CYP2E1 :
Cytochrome P450 2E1
DNA
:
Deoxyribonucleic Acid
EGF
:
Epidermal Growth Factor
FEAAs
:
Fatty Acid Ethyl Esters
GPx
:
Glutathione Peroxidase
GR
:
Glutathione Reductase
GSH
:
Gluthathion Sulfur Hidroksil
GSK3β
:
Glycogen Synthase Kinase 3-Beta
GSSG
:
Glutathione Disulfide
H₂O₂
:
Hydrogen Peroxide
HCC
:
Hepatocellular Carcinoma
HGF
:
Hepatocyte Growth Factor
IGF
:
Insulin Like Growth Factor
IL-1
:
Interleukin-1
IL-6
:
Interleukin-6
LPS
:
Lipopolysaccharide
MDA
:
Malondialdehyde
NAD⁺ :
Nikotinamida Adenin Dinukleotida
NADH
:
Nikotinamida Adenosin Dinukleotida Hidrogen
NADPH
:
Nikotinamida Adenin Dinukleotida Fosfat Hidrogen
NF-kB
:
Nuclear Factor Kappa B
IκB
:
Inhibitor Kappa B
NO
:
Nitric Oksida
xv
PDGF
:
Platelet Derived Growth Factor
PI3K
:
Phosphatidylinositol 3-Kinase
ROS
:
Reactive Oxygen Species
S1P
:
Sphingosin-1-Fosfat
SLTA
:
Sekolah Lanjut Tingkat Atas
SLTP
:
Sekolah Lanjut Tingkat Pertama
SGOT
:
Serum Glutamic Oksaloasetat Transaminase
SGPT
:
Serum Glutamic Pyruvat Transaminase
SOD
:
Superoxide Dismutase
SPSS
:
Statistical Product and Service Solutions
STAT3
:
Signal Transducer and Activator of Transkripsi 3
TGF-β
:
Transforming Growth Factor-β
TLR 4
:
Toll-Like Receptor 4
TNF-α
:
Tumor Necrosis Factor Alpha
TNFR1
:
Tumor Necrosis Factor Receptor 1
VEGF
:
Vascular Endothelial Growth Factor
WHO
:
World Health Organization
xvi
DAFTAR LAMPIRAN Lampiran 1: Hasil Pengamatan .......................................................................... 77 Lampiran 2: Hasil Analisis SGOT ..................................................................... 79 Lampiran 3: Hasil Analisis SGPT ...................................................................... 83 Lampiran 4: Dokumentasi Penelitian ................................................................. 87 Lampiran 5: Determinasi Tanaman Biji Anggur Merah .................................... 89 Lampiran 6: Surat Keterangan Ektrak Biji Anggur Merah ................................ 90 Lampiran 7: Surat Keterangan Penelitian .......................................................... 91 Lampiran 8: Surat Keterangan Kelaikan Etik .................................................... 92 Lampiran 9: Kartu Konsultasi Tugas Akhir ....................................................... 93
xvii
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