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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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