KARYA TULIS AKHIR

PENGARUH EKSTRAK DAUN JAMBU BIJI (Psidium guajava L.) DALAM

MENCEGAH PENINGKATAN KADAR BILIRUBIN TOTAL SERUM

PADA TIKUS PUTIH JANTAN (Rattus novergicus strain wistar)

YANG DINDUKSI DENGAN PARASETAMOL

Oleh:

RR. GALUH AGUNG LUKITASARI

09020014

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2013

i

HASIL PENELITIAN

PENGARUH EKSTRAK DAUN JAMBU BIJI (Psidium guajava L.) DALAM

MENCEGAH PENINGKATAN KADAR BILIRUBIN TOTAL SERUM

PADA TIKUS PUTIH JANTAN (Rattus novergicus strain wistar)

YANG DINDUKSI DENGAN PARASETAMOL

KARYA TULIS AKHIR

Diajukan kepada

Universitas Muhammadiyah Malang

untuk Memenuhi Salah Satu Persyaratan

dalam Menyelesaikan Program Sarjana

Fakultas Kedokteran

Oleh:

RR. Galuh Agung Lukitasari

09020014

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2013

ii

LEMBAR PENGESAHAN

LAPORAN HASIL PENELITIAN

Telah disetujui sebagai hasil penelitian

Untuk memenuhi persyaratan

Pendidikan Sarjana Fakultas Kedokteran

Universitas Muhammadiyah Malang

Tanggal: 6 Pebruari 2013

Pembimbing I

dr. Diah Hermayanti, Sp.PK

NIP 196612162005012002

Pembimbing II

dr. Annisa Hanifwati

NIDN 0728117003

Mengetahui,

Fakultas Kedokteran

Dekan,

dr. Irma Suswati, M.Kes

NIP 11395010320

iii

LEMBAR PENGUJIAN

Karya Tulis Akhir oleh RR. Galuh Agung Lukitasari ini telah diuji dan

dipertahankan di depan Tim Penguji pada tanggal 6 Pebruari 2013

Tim Penguji

dr. Diah Hermayanti, Sp.PK Ketua

dr Annisa Hanifwati Anggota

dr. Sulistyo Mulyo Agustini, Sp.PK Anggota

iv

KATA PENGANTAR

Assalamu’alaikum Wr. Wbr.

Puji dan syukur ke hadirat Tuhan Yang Maha Kuasa atas limpahan berkat

dan kasih-Nya, sehingga penulis dapat menyelesaikan Karya Tulis Akhir dengan

judul ”Pengaruh Ekstrak Daun Jambu Biji (Psidium guajava L.) dalam Mencegah

Peningkatan Kadar Bilirubin Total Serum pada Tikus Putih Jantan (Rattus

novergicus strain winstar) yang diinduksi dengan Parasetamol” yang merupakan

salah satu syarat memperoleh gelar kesarjanaan di Fakultas Kedokteran

Universitas Muhammadiyah Malang.

Dengan ini penulis mengucapkan terima kasih kepada semua pihak yang

telah banyak membantu dalam pelaksanaan penelitian hingga penyusunan laporan

ini. Maka pada kesempatan ini, penulis mengucapkan terima kasih kepada:

1. dr Irma Suswati, Mkes, selaku Dekan Fakultas Kedokteran

Universitas Muhammadiyah Malang.

2. dr Meddy Setiawan, SpPD, selaku Pembantu Dekan 1 Fakultas

Kedokteran Universitas Muhammadiyah Malang.

3. dr Fathiyah Safitri, Mkes, selaku Pembantu Dekan 2 Fakultas

Kedokteran Universitas Muhammadiyah Malang.

4. dr Iwan Sys Indrawanto, SpKJ, selaku Pembantu Dekan 3 Fakultas

Kedokteran Universitas Muhammadiyah Malang.

5. dr Diah Hermayanti, SpPK, selaku Pembimbing 1 yang telah

meluangkan waktu dan tenaganya dalam memberikan bimbingan,

nasihat, dan motivasi bagi penulis.

v

6. dr Anisa Hanifwati selaku Pembimbing 2 yang telah meluangkan

waktu untuk memberikan bimbingan dan masukan bagi penelitian ini.

7. dr. Sulistyo Mulyo Agustini, SpPK, selaku Penguji Utama yang telah

sabar menguji dan memberikan saran yang sangat berharga demi

kesempurnaan Karya Tulis Akhir ini.

Penulis sadar bahwa Karya Tulis Akhir ini masih jauh dari sempurna, oleh

karena itu penulis mengharapkan kritik serta sumbang saran di masa mendatang

untuk kesempurnaan dari tugas akhir ini.

Akhir kata semoga Karya Tulis Akhir ini bermanfaat bagi penulis,

pembaca, dan menjadi sumbangan berarti bagi perkembangan ilmu pengetahuan.

Amin.

Wassalamu’alaikum Wr. Wbr.

Malang, 30 Januari 2013

Penulis

vi

UCAPAN TERIMA KASIH

Pada penyusunan Karya Tulis Akhir ini, penulis banyak mendapatkan

bimbingan dan bantuan dari berbagai pihak. Oleh karena itu dalam kesempatan ini

penulis mengucapkan terima kasih kepada.

1. Allah SWT yang telah memberi rahmat, karunia kesehatan, kesabaran dan

lindungan-Nya sehingga penulis dapat menyelesaikan tugas akhir ini

2. Papa (Agung Andokoputro) dan mama (Hari Soeprihatiningsih) atas segala

dukungan baik moril maupun materiil. Kalian adalah cahaya kehidupan, tanpa

kalian saya tidak bisa seperti ini sekarang.

3. Adik Ayu dan Agi (cumil), eyang uti, keluarga besar papa dan mama atas

dukungan, doa, semangat, dan cinta kasih yang telah kalian berikan.

4. Seluruh dosen pengajar, staf TU, dan karyawan Fakultas Kedokteran

Universitas Muhammadiyah Malang yang telah memberikan bekal ilmu dan

pengetahuan serta segala fasilitas dalam penelitian ini.

5. Mas Didin, mbak Kiki beserta seluruh staf laboratorium Faal FK UB, Mbak

Susi dan staf laboratorium Kimia Farmasi UMM atas segala bantuan dan

bimbingannya dalam menjalankan penelitian.

6. Septika Purnastuti dan Heru Pratomo selaku partner kerja dalam penelitian

7. Teman-teman saya Diana, Ulfa, Ivo, Frida, Pras, Dewi, Harin, Winda, Devi,

Mbak Yulia, Ayu, Bella, Indah, Amel, Anggi, Danis, Mbak Mayang, Mbak

Nia, Latifa, Anita, Apip, Yudha, Fadhiel, keluarga besar SM khususnya Tya

dan Erlina, TBMM Nurul Qolbi, dan KKN 65 2012/2013 serta seluruh teman

FK UMM angkatan 2009/2010 yang tidak bisa saya sebutkan satu persatu,

terimakasih atas dukungan dan semangat yang diberikan kepada penulis.

vii

ABSTRAK

Lukitasari, RR Galuh Agung. 2013. Pengaruh Esktrak Daun Jambu Biji (Psidium

guajava L.) terhadap Pencegahan Peningkatan Kadar Bilirubin Total Serum

Tikus Putih Jantan (Rattus novergicus strain wistar) yang diinduksi

Parasetamol. Fakultas Kedokteran Universitas Muhammadiyah Malang.

Pembimbing: (I) Diah Hermayanti, (II) Annisa Hanifwati.

Latar Belakang: Daun jambu biji (Psidium guajava L.) mengandung tanin dan

quersetin yang berfungsi sebagai antioksidan dan detoksifikasi hepatotoksisitas

imbas obat. Parasetamol adalah obat yang sering menyebabkan heptotoksisitas

dengan mekanisme metabolit alkilasi minor NAPQI dan radikal bebas ion

superoksida.

Tujuan: Membuktikan pengaruh ekstrak daun jambu biji (Psidium guajava L.)

terhadap pencegahan peningkatan kadar bilirubin total serum tikus putih

Metode: Eksperimental murni, The Post Test Only Control Group Design.

Sampel dibagi 5 kelompok. Kelompok 1 (kontrol negatif), kelompok 2 (kontrol

positif) diberi parasetamol 200 mg/ekor pada hari ke 10, dan 3 kelompok diberi

ekstrak daun jambu biji (Psidium guajava L.) dosis 250 mg/kgBB, 500 mg/kgB,

750 mg/kgBB selama 9 hari. Dianalisis dengan uji Kruskall-Wallis, uji korelasi,

dan uji regresi.

Hasil penelitian dan diskusi: Uji Kruskall-Wallis, tidak ada perbedaan (p>0,05).

Analisis korelasi (p=0,018) dan (r=-0,601), kenaikan dosis ekstrak daun jambu

biji (Psidium guajava L.) dapat mencegah peningkatan kadar bilirubin total serum.

Hasil analisis regresi, pemberian ekstrak daun jambu biji (Psidium guajava L.)

berpengaruh terhadap pencegahan peningkatan kadar bilirubin total serum

(R2=0,361)

Kesimpulan: Pemberian ekstrak daun jambu biji (Psidium guajava L.) dapat

mencegah peningkatan kadar bilirubin total serum tikus putih jantan (Rattus

novergicus strain wistar) yang diinduksi parasetamol.

Kata kunci: Ekstrak Daun Jambu Biji, Bilirubin total serum, Parasetamol

viii

ABSTRACT

Lukitasari, RR Galuh Agung. 2013. Effect of Extract Guava Leaf (Psidium

guajava L.) for Improved Prevention Total Serum Bilirubin Levels of White

Male Rat (Rattus novergicus strain wistar) Paracetamol-induced. Medical

Faculty Muhammadiyah University of Malang. Advisors: (I) Diah

Hermayanti, (II) Annisa Hanifwati.

Background: Guava leaf (Psidium guajava L.) contains of tannin and quercetin

that have function as antioxidant and detoxcification drug induced hepatotoxic.

Paracetamol is a drug that often cause hepatotoxicity by mechanism of minor

alcylating metabolit NAPQI and free radical superoxide ions.

Objective: Proving the influence Psidium guajava leaf extract for increased

prevention total serum bilirubin levels white male rats (Rattus novergicus strain

wistar)

Methode: True experimental, The Post Test Only Control Group Design. The

sample was divided into 5 groups. Group 1 (negative control), Group 2 (postive

control) were given paracetamol 200 mg/tail in the 10th

day, and 3 other groups

were given Psidium guajava leaf extract dose 250 mg/weight, 500 mg/weight 750

mg/weight during 9 days. Analyzed using Kruskal-Wallis, correlation and

regression test.

Result and discussion: Kruskall-Wallis test, not significant (p>0.05). Correlation

analysis, (p=0.018) and (r=-0.601) does increased dose Psidium guajava leaf

extract to prevent an increase in total serum bilirubin levels. Regression analysis,

guava leaf extract (Psidium guajava L.) prevent an increase in total serum

bilirubin levels (R2= 0.361)

Conclusion: The extract of guava leaves (Psidium guajava L.) prevent an

increase in total serum bilirubin levels of male white rats (Rattus novergicus

wistar strain) paracetamol-induced

Keywords: Guava Leaf Extract, Total Serum Bilirubin, Paracetamol

ix

DAFTAR ISI

LEMBAR PENGESAHAN.................................................................................... ii

LEMBAR PENGUJIAN........................................................................................ iii

KATA PENGANTAR........................................................................................... iv

UCAPAN TERIMA KASIH.................................................................................. vi

ABSTRAK............................................................................................................ vii

ABSTRACT........................................................................................................... viii

DAFTAR ISI.......................................................................................................... ix

DAFTAR TABEL................................................................................................. xii

DAFTAR GAMBAR........................................................................................... xiii

DAFTAR SINGKATAN..................................................................................... xiv

DAFTAR LAMPIRAN........................................................................................ xvi

BAB 1. PENDAHULUAN..................................................................................... 1

1.1 Latar Belakang.................................................................................... 1

1.2 Rumusan Masalah............................................................................... 2

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 klinis........................................................................... 3

1.4.2 Manfaat akademis..................................................................... 3

1.4.3 Manfaat masyarakat.................................................................. 4

BAB 2. TINJAUAN PUSTAKA............................................................................ 5

2.1 Hepar................................................................................................... 5

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

2.1.2 Anatomi sistem bilier dan kandung empedu............................. 6

2.1.3 Fisiologi hepar.......................................................................... 8

2.1.4 Metabolisme bilirubin............................................................. 10

2.1.5 Patofisiologi ikterus................................................................ 13

2.1.6 Hepatotoksisitas imbas obat.................................................... 17

2.1.6.1 Metabolisme obat....................................................... 17

x

2.1.6.2 Mekanisme hepatotoksisitas....................................... 20

2.2 Parasetamol....................................................................................... 25

2.2.1 Sifat farmakologis................................................................... 25

2.2.2 Farmakokinetik parasetamol................................................... 25

2.2.3 Indikasi dan dosis.................................................................... 26

2.2.4 Hepatotoksisitas parasetamol.................................................. 27

2.3 Mekanisme Hepatotoksisitas Parasetamol........................................ 28

2.4 Daun Jambu Biji............................................................................... 31

2.2.1 Taksonomi............................................................................... 31

2.2.2 Morfologi daun jambu biji...................................................... 31

2.2.3. Kandungan kimia dan manfaat.............................................. 32

2.5 Mekanisme Daun Jambu Biji (Psidium guajava L) dalam

Menurunkan Kadar Total Bilirubin Serum….....…....….......…........ 34

BAB 3. Kerangka Konseptual dan Hipotesis Penelitian....................................... 35

3.1 Kerangka Konseptual........................................................................ 35

3.2 Hipotesis Penelitian.......................................................................... 39

BAB 4. METODE PENELITIAN ........................................................................ 40

4.1 Jenis Penelitian.................................................................................. 40

4.2 Waktu dan Tempat Penelitian........................................................... 40

4.3 Populasi dan Sampel......................................................................... 40

4.3.1 Populasi.................................................................................... 40

4.3.2 Sampel...................................................................................... 40

4.3.3 Estimasi besar sampel.............................................................. 41

4.3.4 Teknik pengambilan sampel.................................................... 42

4.3.5 Karakteristik sampel penelitian................................................ 42

4.3.5.1 Kriteria inklusi............................................................ 42

4.3.5.2 Kriteria eksklusi.......................................................... 43

4.3.6 Variabel penelitian.................................................................. 43

4.3.6.1 Variabel bebas............................................................ 43

4.3.6.2 Variabel terikat........................................................... 43

4.3.7 Definisi operasional variabel.................................................. 43

4.4 Alat dan Bahan Penelitian................................................................. 44

xi

4.5 Prosedur Penelitian........................................................................... 47

4.6 Analisis Data..................................................................................... 55

4.7 Alur Penelitian.................................................................................. 56

BAB 5. HASIL PENELITIAN DAN ANALISIS DATA.................................... 57

5.1 Hasil Penelitian................................................................................. 57

5.1.1 Bilirubin total serum................................................................ 57

5.2 Analisis Data..................................................................................... 58

5.2.1 Analisis data kadar bilirubin total serum

dengan uji Kruskall Wallis....................................................... 58

5.2.2 Hasil uji lanjut Mann-Whitney................................................. 59

5.2.3 Hasil uji korelasi...................................................................... 60

5.2.4 Hasil uji regresi........................................................................ 60

BAB 6. PEMBAHASAN...................................................................................... 62

BAB 7. KESIMPULAN DAN SARAN................................................................ 69

7.1 Kesimpulan....................................................................................... 69

7.2 Saran................................................................................................. 69

DAFTAR PUSTAKA........................................................................................... 70

LAMPIRAN.......................................................................................................... 74

xii

DAFTAR TABEL

Tabel Halaman

2.1 Taksonomi Daun Jambu Biji (Psidium guajava L.)........................................ 31

2.2 Kandungan Hasil Ekstraksi Daun Jambu Biji (Psidium guajava L.).............. 33

5.1 Kadar Serum Bilirubin Total (mg/dl) Tikus Putih.......................................... 57

5.2 Hasil Analisis Data Kadar Bilirubin Total dengan Uji Kruskall Wallis......... 58

5.3 Hasil Uji Lanjut Mann-Whitney Bilirubin....................................................... 59

5.4 Tabel Notasi Berdasarkan Uji Mann-Whitney................................................ 59

5.5 Hasil Analisis Data Kadar Bilirubin Total dengan Uji Korelasi.................... 60

xiii

DAFTAR GAMBAR

Gambar Halaman

2.1 Anatomi Hepar Permukaan Inferior............................................................ 5

2.2 Anatomi Kandung Empedu dan Sistem Biliaris......................................... 6

2.3 Metabolisme Bilirubin.............................................................................. 10

2.4 Jalur Detoksifikasi..................................................................................... 17

2.5 Mekanisme Hepatotoksisitas..................................................................... 21

2.6 Mekanisme Hepatotoksisitas Parasetamol................................................ 28

2.7 Mekanisme Pertahanan Tubuh.................................................................. 30

2.8 Daun Jambu Biji (Psidium guajava L.)..................................................... 31

3.1 Skema Kerangka Konseptual.................................................................... 35

4.1 Bagan Alur Penelitian............................................................................... 56

5.1 Tomografik Hasil Penelitian Kadar Bilirubin Total................................. 58

5.2 Kurva Hubungan antara Dosis Ekstrak Daun Jambu Biji dengan Kadar

Bilirubin Total........................................................................................... 61

xiv

DAFTAR SINGKATAN

AALSD : American Association for the Study of Liver Disease

ALP : Alkaline Phosphatase

ALT : Alanine Transferase

ANOVA : ANalysis Of VAriance between groups

AST : Asparte Aminotransferase

ATP : Adenosine Triphosphat

BB : Berat Badan

BM : Berat Molekul

BR 1 : Broiler 1

CBD : Common Bile Duct

CCl4 : Carbon TetraChloride

CD : Cystic Duct

CHD : Common Hepatic Duct

Cl- : Chloride

CN-I : Crigel Najar I

CN-II : Crigel Najar II

CYP1A2 : Cytochrome P1A2

CYP2A6 : Cytochrome P2A6

CYP2D6 : Cytochrome P2D6

CYP2E1 : Cytochrome P2E1

CYP3A4 : Cytochrome P3A4

DNA : Deoxyrybo Nuclei Acid

FDA : Food and Drug Administration

GSH : Glutamate Systein Glysin

GST : Gluthathione S Transferase

HA : Hepatic Artery

IL-1β : Interleukin-1β

IU : International Unit

IVC : Inferior Vena Cava

LHA : Left Hepatic Artery

xv

LHD : Left Hepatic Duct

LHV : Left Hepatic Vein

LPV : Left Portal Vein

MHV : Middle Hepatic Vein

MMP9 : Matrix Metalloproteinase-9

mRNA : messenger-Ribonuclei Acid

MRP3 : Multi Drug Resitance Accociated Protein 3

Na+ : Natrium

NADH : Nicotinamide Adenine Dinucleotide Oxidase

NADPH : Nicotinamide Adenine Dinucleotide Phosphate-Oxidase

NAPQI : N- Acetyl-P-benzoquionon-Imin

NQO1 : NAD(P)H quione oxidoreductase

NSAID : Non Steroid Anti Inflamation Drug

OAINS : Obat Anti Inflamasi Non Steroid

PV : Portal Vein

RES : Reticuloendothelial System

RHA : Right Hepatic Artery

RHD : Right Hepatic Duct

RHV : Right Hepatic Vein

RNA : Ribonuclei Acid

RPV : Right Portal Vein

ROS : Reactive Oxygen Species

SH : Sulfhydryl

TGF-β : Transforming Growth Factor-β

TNF : Tumor Necrosis Factor

TNF α : Tumor Necrosis Factor α

xvi

DAFTAR LAMPIRAN

Lampiran Halaman

1. Output Statistik.......................................................................................... 74

2. Dokumentasi Penelitian............................................................................. 80

3. Hasil Laboratorium Kadar Bilirubin......................................................... 82

4. Surat Keterangan Penelitian...................................................................... 83

5. Kartu Konsultasi Tugas Akhir................................................................... 84

6. Kartu Mengikuti Seminar Proposal........................................................... 86

xvii

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