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KARYA TULIS AKHIR

Pengaruh Pemberian Ekstrak Cacing Tanah (Lumbricus rubellus) Peroral

Terhadap Kadar Enzim SOD dan Pertanda Inflamasi Kronis Esofagus Tikus

Putih Jantan Wistar yang Diinduksi oleh DMBA Sebagai Agen

Karsinogenik

Disusun oleh :

SISMI YUNIARTI

09020127

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2013

HASIL PENELITIAN

Pengaruh Pemberian Ekstrak Cacing Tanah (Lumbricus rubellus) Peroral

Terhadap Kadar Enzim SOD dan Pertanda Inflamasi Kronis Esofagus Tikus

Putih Jantan Wistar yang Diinduksi oleh DMBA Sebagai Agen

Karsinogenik

KARYA TULIS AKHIR

Diajukan kepada Universitas Muhammadiyah

Malang untuk Memenuhi Salah Satu

Persyaratan dalam Menyelesaikan Program

Sarjana Fakultas Kedokteran

Oleh :

Sismi Yuniarti

09020127

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2013

i

LEMBAR PENGESAHAN

LAPORAN HASIL PENELITIAN

Telah disetujui sebagai hasil penelitian

untuk memenuhi persyaratan

Pendidikan Sarjana Fakultas Kedokteran

Universitas Muhammadiyah Malang

Tanggal: 22 Maret 2013

Pembimbing I

dr. Fathiyah Safithri, M. Kes

Pembimbing II

dr. Maryam Abdullah

Mengetahui,

Fakultas Kedokteran

Dekan,

dr. Irma Suswati, M.Kes

ii

LEMBAR PENGUJIAN

Karya Tulis Akhir oleh Sismi Yuniarti ini

Telah diuji dan dipertahankan di depan Tim Penguji

Pada tanggal 03 Agustus 2013

Tim Penguji

dr. Fathiyah Safithri, M. Kes, Ketua

dr. Maryam Abdullah , Anggota

Prof. Dr.dr. Djoni Djunaedi, Sp.PD., KPTI Anggota

iii

KATA PENGANTAR

Bismillahirahmanirrahim. Alhamdulillahirabbil’alamin, puji syukur

penulis panjatkan kehadiran Allah SWT karena atas rahmat dan hidayah-Nya,

penulisan tugas akhir ini dapat diselesaikan dengan baik. Shalawat serta salam

selalu tercurahkan kepada Rasulullah SAW, keluarga, para sahabat dan pengikut

beliau hingga akhir zaman.

Penelitian dalam tugas akhir ini berjudul “Pengaruh Pemberian Ekstrak

Cacing Tanah (Lumbricus rubellus) Peroral Terhadap Kadar Enzim SOD dan

Pertanda Inflamasi Kronis Esofagus Tikus Putih Jantan Wistar yang Diinduksi

oleh DMBA Sebagai Agen Karsinogenik”. Tugas akhir ini diajukan untuk

memenuhi persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas

Muhammadiyah Malang.

Pada kesempatan ini, penulis menyampaikan terima kasih yang sebesar-

besarnya kepada:

1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran Universitas

Muhammadiyah Malang atas bimbingannya selama di FK UMM.

2. dr. Fathiyah Safithri selaku pembimbing I, atas bimbingan dan kesabarannya

serta semangatnya dari awal memasuki FK UMM hingga penulis dapat

menyelesaikan penelitian ini dengan baik.

3. dr. Maryam Abdullah selaku pembimbing II, atas bimbingan dan

kesabarannya sehingga saya dapat menyelesaikan penelitian ini dengan baik.

4. Prof. Dr.dr. Djoni Djunaedi, Sp.PD., KPTI, selaku dosen penguji yang

berkenan meluangkan waktu untuk menguji, membimbing, dan mengoreksi

iv

serta memberikan motivasi kepada penulis dalam menyelesaikan karya tulis

akhir ini.

5. Dr. Soebarkah, Sp.PA, selaku konsultan penelitian dalam menyelesaikan

karya tulis akhir.

6. Staff TU yang telah membantu alam kelancaran ujian karya tulis akhir.

7. Semua pihak yang tidak dapat penulis sebutkan satu persatu.

Penulis menyadari sepenuhnya bahwa tidak ada sesuatu yang sempurna di

dunia ini sehingga penulis sangat mengharapkan masukan dari berbagai pihak.

Semoga tugas akhir ini sebagai suatu karya tulis ilmiah dapat bermanfaat bagi

semua pihak.

Malang, Agustus 2013

Penulis

v

ABSTRAK

Yuniarti, Sismi 2013. Pengaruh Pemberian Ekstrak Cacing Tanah (Lumbricus

rubellus) terhadap Kadar Enzim SOD dan Pertanda Inflamasi Kronik

pada Tikus Wistar Jantan yang Diinduksi DMBA. Tugas Akhir.

Fakultas Kedokteran, Universitas Muhammadiyah Malang.

Pembimbing: (I) Fathiyah Safithri * (II) Maryam Abdullah**

Latar Belakang:Kanker Esofagus merupakan keganasan dengan prognosis buruk.

DMBA merupakan salah agen karsinogen dari golongan PAH, yang dapat

menyebabkan reaksi inflamasi pada epitel esofagus. Cacing tanah (Lumbricus

rubellus) yang mengandung polifenol sebagai antiinflamasi dan antioksidan untuk

mencegah kanker esofagus.

Tujuan: Membuktikan adanya pengaruh pemberian ekstrak cacing tanah

(Lumbricus rubellus) terhadap pertanda inflamasi kronik dan kadar enzim SOD

esofagus tikus wistar jantan yang diinduksi oleh agen karsinogen DMBA.

Metode: Eksperimental dengan rancangan the post test only control group design.

Sampel terbagi dalam 5 kelompok yaitu kelompok 1 (tanpa perlakuan); kelompok

2 (DMBA 20 mg/kgBB); kelompok 3, kelompok 4, dan kelompok 5 dinduksi

DMBA 20 mg/kgBB dan ekstrak cacing tanah (150, 300, dan 600 mg/kgBB).

Penelitian ini dilakukan selama ±4 bulan. Analisis data menggunakan uji one way

ANOVA, uji Post Hoc Tukey-HSD, uji korelasi Pearson.

Hasil Penelitian dan Diskusi: Uji one way ANOVA diperoleh p=0,000 (p<0,05),

terdapat perbedaan efek pemberian ekstrak cacing tanah (Lumbricus rubellus)

yang signifikan terhadap kadar enzim SOD dan jumlah sel MN esofagus tikus

putih jantan wistar. Hal ini karena kandungan polifenol dalam ektrak cacing tanah

(Lumbricus rubellus).

Kesimpulan: Ekstrak cacing tanah (Lumbricus rubellus) dapat menurunkan

jumlah sel MN dan menigkatkan kadar enzim SOD dengan menginduksi enzim

SOD endogen dan menghambat COX2.

Kata Kunci: Kanker esofagus, inflamasi kronik, SOD, DMBA, Lumbricus

rubellus.

*Staff pengajar Farmakologi FK UMM

**Staff pengajar FK UMM

vi

ABSTRACT

Yuniarti, Sismi 2013. The Influence of Earthworm Extract (Lumbricus rubellus)

toward the SOD Enzyme Level and Sign of Chronic Inflammation

in Male White Wistar Rat that Induced by DMBA. Final

Assignment, Medical Faculty, University of Muhammadiyah

Malang, (I) Advisor: Fathiyah Safithri * (II) Maryam Abdullah**.

Background: Esophageal Cancer is a malignance with fatal prognosis. DMBA is

carcinogenic agent from PAH group, it causes an inflammation reaction at

esophageal epithelial. Earthworm (Lumbricus rubellus) contains polyphenolic as

antiinflamatory and antioxidant to prevent esophageal cancer.

Objective: Determine the effect of Earthworm extract (Lumbricus rubellus)

toward the Sign of Chronic Inflammation and SOD Enzyme Level in Male

Wistar Rat that Induced by DMBA.

Methods: This study is the posttest only control group design, using five groups

wistar rats. Group 1 untreated ; Group 2 (DMBA 20 mg/kgBW); Group 3, Group

4, and Group 5 induced by DMBA 20 mg/kgBW and earthworm extract (150,

300, and 600 mg/kgBW). The research has done for ±4 months. Analized by one

way ANOVA, Post Hoc Tukey-HSD, Pearson correlation test.

Result and Discussion: One way ANOVA obtained p=0,000 (p<0,05), which

mean there were significant differences in the effects of earthworm (Lumbricus

rubellus) extract to SOD enzyme level and number MN cell in white male rats

esophagus. It caused by the polyphenolic compound in the earthworm extract.

Conclusion : The earthworm (Lumbricus rubellus) extract can increase SOD

enzyme level and decrease the number of MN cell in esophageal epithelial by

induce endogenous SOD enzyme and inhibit COX2.

Keywords: Esophageal cancer, chronic inflammation, SOD, DMBA, Lumbricus

rubellus.

* Lecturer of Pharmacology, Medical Faculty of Muhammadiyah Malang

University

** Lecturer, Medical Faculty of Muhammadiyah Malang University

vii

DAFTAR ISI

Halaman

LEMBAR PENGESAHAN ............................................................................. i

LEMBAR PENGUJIAN ................................................................................. ii

KATA PENGANTAR .................................................................................... iii

ABSTRAK ..................................................................................................... v

ABSTRACT ................................................................................................... vi

DAFTAR ISI ................................................................................................. vii

DAFTAR TABEL .......................................................................................... xi

DAFTAR GAMBAR ...................................................................................... xii

DAFTAR SINGKATAN ................................................................................ xiii

DAFTAR LAMPIRAN .................................................................................. xv

BAB I PENDAHULUAN

1.1 Latar Belakang Masalah .......................................................... 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 .................................................................. 3

1.4.1 Manfaat Akademik ......................................................... 3

1.4.2 Manfaat Klinis ............................................................... 4

viii

BAB II TINJAUAN PUSTAKA

2.1 Esofagus Normal ..................................................................... 5

2.1.1 Anatomi ......................................................................... 5

2.1.2 Fisiologi Pertahanan Mukosa Esofagus .......................... 6

2.1.3 Perbaikan Epitel ............................................................. 7

2.1.4 Histologi ........................................................................ 8

2.1.5 Faktor Yang Mempengaruhi Kerusakan Esofagus .......... 11

2.2 Kanker Esofagus ..................................................................... 13

2.2.1 Etiologi .......................................................................... 13

2.2.2 Patofisiologi ................................................................... 15

2.3 7,12-dimetilbenz(a) antrasen (DMBA) .................................... 34

2.4 Senyawa Kemopreventif ......................................................... 38

2.5 Cacing Tanah Lumbricus rubellus ........................................... 40

2.5.1 Taksonomi ..................................................................... 40

2.5.2 Kandungan Kimia Lumbricus rubellus .......................... 41

2.5.3 Karakteristik Lumbrokinase ........................................... 42

2.5.4 Efek Farmakologis Ekstrak Lumbricus rubellus ............. 42

BAB III KERANGKA KONSEP DAN HIPOTESIS PENELITIAN

3.1 Kerangka Konsep .................................................................... 45

3.2 Hipotesis ................................................................................. 47

BAB IV METODOLOGI PENELITIAN

4.1 Rancangan Penelitian .............................................................. 48

ix

4.2 Lokasi dan Waktu Penelitian ................................................... 48

4.3 Populasi dan Sampel Penelitian ............................................... 48

4.3.1 Populasi ......................................................................... 48

4.3.2 Sampel .......................................................................... 48

4.3.3 Estimasi Besar Sampel ................................................... 48

4.3.4 Karakteristik Sampel Penelitian ...................................... 49

4.4 Variabel Penelitian .................................................................. 49

4.4.1 Variabel Bebas ............................................................... 49

4.4.2 Variabel Tergantung ...................................................... 50

4.4.3 Variabel Kontrol ............................................................ 50

4.4.4 Definisi Operasional Variabel ........................................ 50

4.5 Alat dan Bahan Penelitian ....................................................... 51

4.6 Alur Penelitian ........................................................................ 54

4.7 Prosedur Penelitian................................................................... 55

4.7.1 Adaptasi Hewan Coba .................................................... 55

4.7.2 Pemberian Ekstrak cacing tanah ..................................... 55

4.7.3 Induksi DMBA .............................................................. 56

4.7.4 Perlakuan pada Hewan Coba .......................................... 56

4.7.5 Pemeriksaan Histopatologi dengan Metode Pengecatan

Hematoksilin Eosin (HE) ............................................... 58

4.7.6 Pengamatan Hasil ........................................................... 60

4.8 Analisis Data ........................................................................... 60

4.9 Jadwal Penelitian ..................................................................... 61

x

BAB 5 HASIL PENELITIAN DAN ANALISIS DATA ................................. 62

BAB 6 PEMBAHASAN ................................................................................. 72

BAB 7 KESIMPULAN DAN SARAN ........................................................... 79

DAFTAR PUSTAKA .................................................................................... 80

LAMPIRAN ................................................................................................... ....... 94

xi

DAFTAR TABEL

Halaman

Tabel 4.1 Jadwal Penelitian............................................................................. 61

xii

DAFTAR GAMBAR

Halaman

Gambar 2.1 Lapisan Epitel Esofagus ........................................................... 9

Gambar 2.2 Lapisan Esofagus ....................................................................... 10

Gambar 2.3 Model Perkembangan Kanker .................................................. 21

Gambar 2.4 Patogenesis Karsinoma Esofagus ............................................. 23

Gambar 2.5 Peran Inflamasi dalam perkembangan karsinoma ..................... 27

Gambar 2.6 Reaksi Haber-Weiss ................................................................ 29

Gambar 2.7 Pembentukan H2O2 pada Reduksi O2 Menjadi H2O ................. 30

Gambar 2.8 Jalur metabolisme DMBA ........................................................ 36

Gambar 2.9 Lumbricus rubellus................................................................... 40

xiii

DAFTAR SINGKATAN

5-HT : 5-Hydroxytryptamine

ADC : Adenocarcinoma

CaMP : Cyclic Adenosine Monophosphate

CYP1A1 : Cytochrome P450 Family 1 Subfamily A Polypeptide 1

CYP1B1 : Cytochrome P450 Family 1 Subfamily B Polypeptide 1

CMC-Na : Carboxymethylcellulose- Natrium

CAT : Catalase

COX : Cyclooxygenase

COX-2 : Cyclooxygenase -2

DMBA : 7,12-Dimethylbenz(a) anthracene

DNA : Deoxyribo Nucleic Acid

ECT : Ekstrak cacing tanah

EFE : Earthworm Fibrinolytic Enzime

EGF : Endothelial Growth Factor

GERD : Gastroesophageal Reflux Disease

Gpx : Gluthathione Peroxidase

GSH : Glutation Sulfur Hidroksil

GST : Gluthatione S-Transferase

HE : Hematoxylin and Eosin

IFN- : Interferon-Gamma

IL-1 : Interleukin-1 Beta

xiv

LES : Lower Esophageal Sphincter

LP : Lapang Pandang

MN : Mononuklear

MTT : Methylthiazol Tetrazolium

NADPH : Nicotinamide Adenine Dinucleotide Phosphate

NBT : Nitroblue Tetrazolium

Nf-kB : Nuclear Factor-Kappa B

NO : Nitric Oxide

PAH : Polycyclic Aromatic Hydrocarbon

ROS : Reactive Oxygen Species

SCC : Squamous Cell Carcinoma

TBARS : Thiobarbituric Acid Reactive Substance

TNF-α : Tumor Necrosis Factor Alpha

xv

DAFTAR LAMPIRAN

Halaman

Lampiran Penelitian Pendahuluan.................................................................... .. 75

80

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