KARYA TULIS AKHIR PERBANDINGAN EFEKTIVITAS … · SGPT Pada Tikus Putih Jantan Strain Wistar Yang...
-
Upload
nguyenkiet -
Category
Documents
-
view
228 -
download
0
Transcript of KARYA TULIS AKHIR PERBANDINGAN EFEKTIVITAS … · SGPT Pada Tikus Putih Jantan Strain Wistar Yang...
KARYA TULIS AKHIR
PERBANDINGAN EFEKTIVITAS EKSTRAK PROPOLIS DAN MADU
SEBAGAI ANTIOKSIDAN TERHADAP PERUBAHAN KADAR SGOT DAN
SGPT PADA TIKUS PUTIH JANTAN STRAIN WISTAR YANG DIINDUKSI
KARBON TETRAKLORIDA ( CCL4)
OLEH :
NAMA: WULAN DEWI FARICHAH
NIM : 201010330311075
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2014
ii
HASIL PENELITIAN
PERBANDINGAN EFEKTIVITAS EKSTRAK PROPOLIS DAN MADU
SEBAGAI ANTIOKSIDAN TERHADAP PERUBAHAN KADAR SGOT
DAN SGPT PADA TIKUS PUTIH JANTAN STRAIN WISTAR YANG
DIINDUKSI KARBON TETRAKLORIDA ( CCL4)
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
untuk Memenuhi Salah Satu Persyaratan
dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh :
WULN DEWI FARICHAH
201010330311O75
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2014
iii
LEMBAR PENGESAHAN
KARYA TULIS AKHIR
Telah disetujui sebagai hasil penelitian
untuk memenuhi persyaratan
Pendidikan Sarjana Fakultas Kedokteran
Universitas Muhammadiyah Malang
Tanggal : 10 Juli 2014
Pembimbing I,
dr. Sulistyo Mulyo Agustini, Sp.PK
Pembimbing II,
dr. Maryam Abdullah
Mengetahui,
Dekan Fakultas Kedokteran
Universitas Muhammadiyah Malang
dr. Irma Suswati, M.Kes
iv
LEMBAR PENGUJIAN
Karya Tulis Akhir oleh Wulan Dewi Farichah ini
telah diuji dan dipertahankan di depan tim penguji
pada hari Senin, tanggal 10 Juli 2014
Tim Penguji
dr. Sulistyo Mulyo Agustini, Sp.PK , Ketua
dr. Maryam Abdullah , Anggota
dr. Rubayat Indradi, MOH , Anggota
v
KATA PENGANTAR
Segala puji hanya bagi Allah SWT karena hanya dengan limpahan rahmat
serta karunia-Nya penulis mampu menyelesaikan tugas akhir yang berjudul
“Perbandinagn Efektivitas Ekstrak Propolis dan Madu Sebagai Antioksidan
Terhadap Perubahan Kadar SGOT dan SGPT Pada Tikus Putih (Rattus
novergicus) Strain Wistar yang Diinduksi Karbon Tetraklorida (CCl4)”
Dengan terselesaikannya tugas akhir ini, penulis mengucapkan terimakasih
kepada:
1. Allah SWT, Berkat rahmat dan petunjuk-Nya sehingga penulis dapat
menyelesaikan tugas akhir ini.
2. dr. Rubayat Indradi, MOH, selaku penguji yang telah memberikan saran
perbaikan untuk tugas akhir ini.
3. dr. Sulistyo Mulyo Agustini, Sp. PK, selaku pembimbing I yang telah
memberi bimbingan, saran, dan masukan sehingga saya dapat
menyelesaikan tugas akhir ini.
4. dr. Maryam Abdullah, selaku pembimbing II yang dengan sabar
membimbing dan senantiasa memberi semangat, sehingga saya dapat
menyelesaikan tugas akhir ini.
5. Keluarga saya, yang telah memberi dukungan baik moral ataupun materiil
dalam penyelesaian tugas akhir ini.
6. Genio Rachmadana (Cime) yang telah berkontribusi dalam berbagai hal
yang tidak bisa disebutkan semuanya dalam proses pengerjaan tugas akhir
ini.
vi
7. Devita Ari Pratiwi (Ipik), Nurul Atika Az-Zahra (Itik), Dywangga
Aulianisa (Didi/Miss Online Shop), Siti Khoirun Nisak (Enis), Nur Aisha
Ibrahimiyah (Ka Sha), selaku sahabat, orang terdekat dan teman
bimbingan yang setia menemani dan membantu memperbaiki kekurangan
dalam setiap proses pengerjaan tugas akhir ini.
8. Mbak Fat, Pak Kus, Mas Miftah, Mas Nyono, Mas Joko laboran FK UMM
yang telah membantu dan membimbing melakukan penelitian ini dengan
hasil yang maksimal dengan penuh kesabaran.
9. Mas Didit, Mas Faisal, Mbak Citra, Mbak Nuke, Pak Yono, dan Bu Endah
selaku pegawai TU FK UMM yang telah membantu dalam setiap proses
demi kelancaran pengerjaan tugas akhir ini.
10. Serta semua kontributor dan teman teman lain yang tidak bisa penulis
sebutkan satu per satu disini
Penulis menyadari bahwa penulisan ini masih jauh dari sempurna, oleh
karena itu penulis tetap membuka diri untuk kritik dan saran yang membangun.
Akhirnya, semoga tugas akhir ini dapat bermanfaat.
Malang, 6 Agustus 2014
Penulis
vii
ABSTRAK
Farichah, Wulan Dewi. 2014. Perbandingan Efektivitas Ekstrak Propolis Dan
Madu Sebagai Antioksidan Terhadap Perubahan Kadar SGOT Dan
SGPT Pada Tikus Putih Jantan Strain Wistar Yang Diinduksi Karbon
Tetraklorida (CCL4). Tugas Akhir, Fakultas Kedokteran Universitas
Muhammadiyah Malang. Pembimbing: (1)Sulistyo Mulyo Agustini*
(2) Maryam Abdullah**.
Latar Belakang: Hepatotoksik merupakan salah satu efek yang timbul akibat
penumpukan zat berbahaya seperti radikal bebas. Ekstrak propolis dan madu
mengandung flavonoid yang berfungsi sebagai antioksidan yang memiliki
kemampuan sebagai hepatoprotektif.
Tujuan: Mengetahui perbandingan efektivitas ekstrak propolis dan madu
terhadap perubahan kadar SGOT (Serum Glutamic Oxaloacetic Transaminase)
dan SGPT (Serum Glutamic Pyruvic Transaminase) pada tikus putih jantan
(Rattus Novergicus) Strain Wistar yang diinduksi Karbontetraklorida (CCl4).
Metode: Penelitian ini merupakan penelitian eksperimental dengan post test only
control group design. Sampel dibagi menjadi delapan kelompok yaitu kontrol
negatif, kontrol positif, tiga kelompok yang diberi ekstrak propolis masing-
masing dengan dosis 100 mg/kgBB/hari, 200 mg/kgBB/hari, dan 300
mg/kgBB/hari, dan tiga kelompok yang diberi madu masing-masing dengan dosis
100 mg/kgBB/hari, 200 mg/kgBB/hari, dan 300 mg/kgBB/hari. Semua kelompok
diinduksi karbon tetraklorida 1 ml/kgBB/3 hari kecuali kontrol negatif. Analisis
data menggunakan One Way ANOVA, uji TUKEY, uji korelasi Pearson, dan uji
regresi linier.
Hasil dan Pembahasan: Efek ekstrak propolis dan madu secara signifikan
mencegah terjadinya peningkatan kadar SGOT dan SGPT dengan nilai sig= 0,000
(p<0,05). Hasil rata-rata kadar SGOT dan SGPT kelompok propolis lebih
mendekati kontrol negatif dibandingkan kelompok madu. Hasil uji TUKEY
didapatkan notasi berbeda antar kelompok. Hasil uji korelasi didapatkan korelasi
negatif dan hubungan sangat kuat baik propolis maupun madu. Semakin tinggi
dosis ekstrak propolis dan madu maka semakin menurun kadar SGOT dan SGPT.
Kesimpulan: Ekstrak propolis memiliki efektivitas hepatoprotektif yang lebih
baik dibandingkan pemberian madu pada tikus yang diinduksi karbon tetraklorida.
Kata Kunci: Ekstrak propolis, madu, SGOT, SGPT
* : Staff pengajar Patologi Klinik FK UMM
** : Staff pengajar FK UMM
viii
ABSTRACT
Farichah, Wulan Dewi. 2014. Comparison Effectivity of Propolis Extract and
Honey as Antioxidant on SGOT and SGPT Level in Male Rat Strain
Wistar Induced by Carbon Tetrachloride (CCl4). Final Assignment,
Medical Faculty of University of Muhammadiyah Malang. Advisor: (1)
Sulistyo Mulyo Agustini* (2) Maryam Abdullah**.
Background: Hepatotoxicity is one of the effect caused by accumulation of
dangerous substances such as free radicals. Propolis extract and honey contain
flavonoid which function as antioxidant for hepatoprotective.
Objective: To compare effectivity of propolis extract and honey as antioxidant in
SGOT and SGPT levels in male rat (Rattus novergicus) Strain wistar induced by
carbon tetrachloride (CCl4).
Method: This research was true experimental using post test only control group
design. Samples were divided into eight groups. The negative control, positive
control, three experimental groups received propolis extract at dose 100
mg/kgBW/day, 200 mg/kgBW/day, and 300 mg/kgBW/day, and three
experimental groups received honey at dose 100 mg/kgBW/day, 200
mg/kgBW/day, and 300 mg/kgBW/day. All groups except negative control group
were induced by carbon tetrachloride 1 ml/kgBW/3 day. Data were analyzed
using One Way ANOVA, TUKEY test, pearson correlation test, and linier
regression.
Result and discussion: Propolis extract and honey significantly prevented the
increases in the SGOT and SGPT levels with sig value = 0,000 (p<0,05). The
mean value SGOT and SGPT levels in propolis extract group approached the
value in negative control. TUKEY test showed different notation between groups.
Correlation test showed strong negative correlation either in propolis or honey.
The higher dose of propolis extract and honey is associated with lower SGOT and
SGPT levels.
Conclusion: Propolis extract had better hepatoprotective effect than honey in rat
induced by carbon tetrachloride.
Keyword: Propolis extract, honey, SGOT, SGPT
* : Teaching Staff of Clinical Pathology in Medical Faculty of UMM
** :Teaching Staff in Medical Faculty of UMM
ix
DAFTAR ISI
HALAMAN JUDUL .............................................................................................ii
LEMBAR PENGESAHAN...................................................................................iii
LEMBAR PENGUJIAN........................................................................................iv
KATA PENGANTAR........................ ...................................................... ............v
ABSTRAK.............................................................................................................vi
ABSTRACT........................ ...................................................................... ...........vii
DAFTAR ISI .......................................................................................................viii
DAFTAR GAMBAR.............................................................................................xi
DAFTAR TABEL ................................................................................................xii
DAFTAR SINGKATAN ......................................................................... ...........xiii
DAFTAR LAMPIRAN…....................................................................................xiv
BAB I PENDAHULUAN
1.1 Latar Belakang .................................................................................... ............1
1.2 Rumusan Masalah .............................................................................. ............2
1.3 Tujuan Penelitian ............................................................................................ 2
1.3.1 Tujuan Umum .................................................................................. 2
1.3.2 Tujuan Khusus .................................................................................. 3
1.4 Manfaat Penelitian .......................................................................................... 3
1.4.1 Manfaat Akademis .............................................................................. 3
1.4.2 Manfaat Klinis .................................................................................... 4
1.4.3 Manfaat Untuk Masyarakat ............................................................... 4
BAB II TINJAUAN PUSTAKA..........................................................................5
2.1 Propolis ........................................................................................................... 5
2.1.1 Pengertian ........................................................................................... 5
2.1.2 Kandungan Propolis ........................................................................... 6
2.1.3 Keamanan Penggunaan Propolis..........................................................8
2.1.4 Pengaruh Propolis sebagai Antioksidan..............................................9
2.2 Madu ............................................................................................................11
2.2.1 Definisi Madu ...................................................................................11
2.2.2 Kandungan Madu..............................................................................12
2.2.3 Pengaruh Madu sebagai Antioksidan ...............................................15
x
2.3 Antioksidan dalam Melawan Radikal Bebas ................................................16
2.3.1 Flavonoid sebagai Antioksidan.........................................................19
2.4 Hepar .............................................................................................................21
2.4.1 Anatomi Hepar..................................................................................21
2.4.2 Fisiologi Hepar .................................................................................23
2.5 Peran Enzim Transaminase pada Kerusakan Hepar......................................25
2.5.1 Serum Glutamic Oxaloasetic Transaminase (SGOT) .......................25
2.5.2 Serum Glutamic Pyruvat Transaminase (SGPT) ..............................26
2.6 Karbon Tetraklorida (CCL4) .........................................................................27
2.6.1 Definisi dan Penggunaan Karbon Tetraklorida ................................27
2.4.2 Mekanisme Hepatotoksik CCL4 .......................................................28
BAB III KERANGKA KONSEP .......................................................................32
3.1 Kerangka Konsep .........................................................................................32
3.2 Hipotesis penelitian .......................................................................................34
BAB IV METODOLOGI PENELITIAN..........................................................35
4.1 Rancangan Penelitian ....................................................................................35
4.2 Lokasi dan Waktu Penelitian ........................................................................35
4.3 Populasi dan Sampel .....................................................................................35
4.3.1 Populasi ............................................................................................35
4.3.2 Sampel ..............................................................................................35
4.3.3 Besar Sampel ....................................................................................35
4.3.4 Karakteristik Sampel Penelitian .......................................................36
4.4 Variabel Penelitian dan Definisi Operasional ...............................................37
4.4.1 Variabel Bebas ..................................................................................37
4.4.2 Variabel Terikat ................................................................................37
4.4.3 Definisi Operasional .........................................................................37
4.5 Alat dan Bahan ..............................................................................................38
4.5.1 Alat ...................................................................................................38
4.5.2 Bahan ................................................................................................39
4.6 Alur Penelitian ..............................................................................................41
4.7 Prosedur Penelitian........................................................................................42
4.7.1 Persiapan hewan coba .......................................................................42
xi
4.7.2 Ekstrak Propolis ................................................................................42
4.7.3 Pembuatan Larutan Madu .................................................................44
4.7.4 Pembagian Kelompok Tikus ............................................................44
4.7.5 Proses Anastesi dan Pembedahan .....................................................45
4.7.6 Proses Penyuntikan Intraperitoneal ..................................................45
4.7.7 Perhitungan SGOT dan SGPT ..........................................................46
4.8 Analisis Data .................................................................................................47
BAB V HASIL PENELITIAN DAN ANALISIS DATA ..................................48
5.1 Hasil Pemeriksaan kadar SGOT....................................................................48
5.2 Hasil Pemeriksaan kadar SGPT ....................................................................49
5.3 Analisis Data .................................................................................................50
5.3.1 Uji Normalitas dan Homogenitas .....................................................50
5.3.2 Uji ANOVA ......................................................................................51
5.3.3 Uji Tukey ..........................................................................................51
5.3.4 Uji Korelasi .......................................................................................52
5.3.5 Uji Regresi ........................................................................................53
BAB VI PEMBAHASAN..................................................................................55
BAB VII KESIMPULAN DAN SARAN ...........................................................60
7.1 Kesimpulan ...................................................................................................60
7.2 Saran ..............................................................................................................60
Daftar Pustaka......................................................................................................61
Lampiran..............................................................................................................67
xii
DAFTAR GAMBAR
Gambar Halaman
2.1 Penampang Melintang Sarang Lebah Madu di dalam Rongga Pohon ....... 6
2.2 Madu .......................................................................................................... 11
2.3 Struktur Kimia Flavonoid .......................................................................... 19
2.4 Makroskopis Hepar Manusia ..................................................................... 21
5.1 Grafik Rata-rata kadar SGOT pada tikus putih jantan ............................... 48
5.2 Grafik Rata-rata kadar SGPT pada tikus putih jantan ................................ 50
xiii
DAFTAR TABEL
Tabel Halaman
2.1 Komposisi Madu per 100 gram.............................................................13
2.2 Komposisi Mineral dan Vitamin dalam Madu......................................14
2.3 Komposisi Kandungan Kimia dalam Madu..........................................14
5.1 Rerata Kadar SGOT..............................................................................48
5.2 Rerata Kadar SGPT...............................................................................49
xiv
DAFTAR SINGKATAN
ATP : Adenosin-5-triphosphat
Ca : Calcium
CAPE : Caffeic acid phenethyl ester
CCl3 O2 : Triklorometilperoxida
CCl3 : Triklorometil
CCL4 : Karbon tetrklorida
HDL : High density lipoprotein
IL-1 : Interleukin -1
IL-6 : Interleukin -6
LDL : Low Density Lipoprotein
MDA : Malonaldehyde
NO : Nitric oxide
NOS : Nitric oxide synthase
SGOT : Serum Glutamic Oxaloacetic Transaminase
SGPT : Serum Glutamic Piruvic Transaminase
TG : Triglyceride
TNF-α : Tumor nekrosis factor- α
VLDL : Very low density lipoprotein
xv
DAFTAR LAMPIRAN
Lampiran 1: Data Hasil Penelitian ................................................................... 67
Lampiran 2: Analisis Data ............................................................................... 68
Lampiran 3: Dokumentasi Kegiatan ................................................................ 76
Lampiran 4: Surat keterangan penelitian ......................................................... 78
xvi
DAFTAR PUSTAKA
Abbouds G, Kaplowitz N, 2007, ‘Pathogenesis of drug induced hepatitis’, Drug
Safety, vol.30, no. 4,pp.286-290.
Abdelsameea, Ahmed A , Laila A. et al. 2013 „Study of The Possible
Hepatoprotective Effect of Propolis against The Hepatotoxic Effect of
Atorvastatin in Albino Rats‟. Study of The Possible Hepatoprotective Effect
of, 15(5) : 388-396.
Ajibola A, Chammunorwa, Joseph P.et al. 2012 „Nutraceutical values of natural
honey and its contribution to human health and wealth‟. Nutrition &
Metabolism, 9(61). Available at: http://www.nutritionandmetabolism.com/
(accessed 27 Februari 2014).
Alagammal, M. Lincy, M.Packia. et al. 2013 „ Hepatoprotective and Antioxidant
effect of Polygala rosmarinifolia Wight & Arn against CCL4 induced
hepatotoxicity in rats‟. Journal of Pharmacognosy and Phytochemistry,
2(1): 118-124.
Al-Waili N. S. 2003. Effects of daily consumption of honey solution on
hematological indices and blood levels of minerals and enzymes in normal
individuals. Journal Of Medicinal Food. Vol 6. No 2. p: 135.
Amirudin, Rifai. 2009 „Fisiologi dan Biokimia Hati‟. In: Sudoyo, Aru W. et al.
eds. Buku Ajar Ilmu Penyakit Dalam. Jakarta:Interna Publishing.
Andrade, R. J., Robles, M., Castener et al.,2007. Assessment of drug-induced
hepatotoxicity in clinical practice : A challenge for gastroenterologist.
World Jornal of Gastroenterol 21: 13 (3): 329-340.
Andriani, Y. 2008. Toksisitas Fraksi Aktif Steroid Ekstrak Daun Jati Belanda (
Guazama Ulmifolia Lamk.) Terhadap Aktivitas AGOT dan SGPT Pada
Tikus Putih. Jurnal Gradien 4(2):365-371.
Bankova V, Trusheva B, dan Popova M, 2008, New developments in propolis
chemical diversity studies (since 2000), In: Orsolich N dan Basic I (eds),
Scientific Evidence of Use of Propolis in Ethnomedicine, Transworld
Research Network, Trivandrum, pp 1-13.
Bogdanov, Stefan. 2012 „Propolis: Composition, Health, Medicine: A Review‟.
Bee Product Science. Available at: www.bee-hexagon.net (diakses 25
Februari 2014) Current Status and Future Prospect‟. International Journal
of Pharmaceutical Sciences Review and Research, 3(1): 91-100.
Crawford, JM 2005, „Liver and biliary tract‟ , in Kumar, Robbins, Cotran (eds.),
Phatologic basis of disease, 7th cdn, Elsevier, New York.
xvii
Depkes RI. 2007. Profil Kesehatan Indonesia. Available at: www.depkes.go.id
(diakses 2 Maret 2014)
El-Beltagi, Hossam. and Mohamed, Heba I. 2013 „Reactive Oxygen Species,
Lipid Peroxidation and Antioxidative Defense Mechanism. Notulae
Botanicae Horti Agrobotanici Cluj-Napoca, 41(1): 44-57.
El-Khayat, Z., Ezzat, A., Arbid, M., Rasheed, W, and Elias,T. 2010. Potential
Effect of Bee Honey and Propolis Against the Toxicity of Ochratoxin A in
Rats. Macedonian Journal of Medical Sciences 2:311-318.
Erguder B. I., Kilicoglu S. S., Namuslu M.,et al. 2008. Honey prevent hepatic
damage induced by obstruction of the common bile duct. World J
Gastroenterol. 14(23): 3729-3732.
European Commision. 2009. Recommendation from the Scientific Committee on
Occupational Exposure Limits for carbon tetrachloride. Luxemburg: Office
for Official Publications of the European Communities.
http://ec.europa.eu/social/ 22 Februari 2014 (11.23).
Fattah A. B. A. 2004. Pengobatan dan Penyembuhan menurut Wahyu Nabi. Alih
Bahasa: Kathur Suhardi. Jakarta: Pustaka As-Sabil, pp: 247-55.
Finstrom, M.S and Spivak, M. 2010 ‘Propolis and bee health: the natural history
and significance of resin use by honey bees’. EDP Science 41(2010): 295-
311.
Galal, Reem M. 2012 ‘Potential Protective Effect of Honey Against Paracetamol-
induced Hepatotoxicity’. Potential Protective Effect of Honey, 15 (1) : 674-
680.
Guo, Shijin. 2011 ‘Chemical composition, biological activity and application in
animal science of propolis- A review’. Advances in Biomedical
Engineering, 1-2: 98-101.
Guyton, AC & Hall, JE 2008, ‘Liver as an organ’ , in Guyton AC & Hall JE
(eds), textbook of medical physiology, 11th edn, Elseveir, Singapore.
Jain, Anshu et al., 2012. ‘Silymarin and naringenin protects nicotine induced
oxidative stress in young rats‟. Oxidants and Antioxidants in Medical
Science, 1(1): 41-49.
Kilicoglu B., Kismet K., Kilicoglu S. S.et al. 2008. Effects of honey as a
scolicidal agent n the hepatobilliary system. World J Gastroenterol. 14(13):
2085-2088.
Kiso, K. Ueno, S., dan Fukuda, Mana, 2012. The Role of Kupffer Cells in Carbon
Tetrachloride Intoxication in Mice. Biological and Pharmaceutical Bulletin
35(6): 980-983.
xviii
Kolankaya, D., Guldeniz, S., Kandriye, S., et al. 2002. Protective effect of turkish
Propolis on alcohol-induced serum lipid changes and liver injury in male
rats. Food chemistry Journal 78:213-21.
Kumar, V. Abbas, A.K. Fausto,N.et al.(Ed.). 2012. Robbins Basic Pathology.
Edisi 9. Philadelphia: Saunders Elsevier.
Kumazawa, S., Usui, Y., Nakamura, J., et al, 2007, Antioxidant activity and
constituents of propolis collected in various areas of China, Food
Chemistry, Vol. 18, 1400-1409.
Kuropatnicki, A.K., Szliszka, E., dan Krol, W. 2013. Historical Aspects of
Propolis Research in Modern Times. Evidence-Based Complementary and
Alternative Medicine, 2013. http://www.hindawi.com/ 24 Februari 2014
(14.03).
Lotfy, Mahmoud. 2006 „ Biological Activity of Bee Propolis in Health and
Disease‟. Asian Pasific Journal of Cancer Prevention, 7: (22-31)
Manibusan, M., J. Jennifer, dan Kopylev, L. 2010. Toxicological Review of
Carbon Tetrachloride. Washington DC: National Center for Environmental
Assessment. www.epa.gov/iris 22 Februari 2014 (12.09).
Martos, M. Viuda., Navajas, Y.R., dan Lopez J. Fernandez. 2008. Functional
Properties of Honey, Propolis, and Royal Jelly. Journal of Food Science
73(9): 117-124.
Mescher, Al . 2010, Junqueira’s basic histology text & atlas, McGraw Hill,
London
Moruk A.K.O., Wigunaningsih. W., Salam A.et al. 2006. Madu Obat dan
Suplemen. Bali: Pak Oles Centre.
Musa, Tariq N., Salih, Nidhal M., dan Ulaiwi, Wisam S. 2012. Detection of Some
Active Compounds in Aquous and Ethanolic Extract of Iraqi Propolis and
Examine Their Antibacterial Effects. Pakistan Journal of Nutrition 11(1):
83-87.
Neil E. F, Paul S P, David C.2005. Cardiovascular Pharmacology. In : Ronald.D.
Miller. ed. Anesthesia. 9th ed. Philadelphia. pp 191-215.
Notoatmodjo, Soekidjo. 2012. Metodologi Penelitian Kesehatan. Jakarta: Rineka
Cipta.
Novilla, A.2011. Aktivitas Antioksidan Ekstrak Propolis Madu Lokal Apis
mellifera. Jurna Kesehatan Kartika hal : 64-72.
Oskouei, Tahereh Eteraf. and Najafi Moslem. (2013) „Traditional and Modern
Uses of Natural Honey in Human Diseases: A Review‟. Iranian Journal
of Basic Medical Sciences, 16(6): 731-742.
Panjaitan, Ruqiah Ganda Putri. dkk, 2007. „Pengaruh Pemberian Karbon
Tetraklorida Terhadap Fungsi Hati dan Ginjal Tikus‟. Makara Kesehatan,
11(1): 11-16.
xix
Parmar SR, Patel HV, Kiran K, 2010, Hepatoproctive Activity of Some Plants
Extract Againts Paracetamol Induced Hepatotoxicity in Rats, Journal of
herbal Medicine and Toxicology, 4 (2):101-106.
Patel, Jay M. (2008) „A Review of Potential Health Benefit of Flavonoid‟.
Undergraduate Research Journal, 3(2). Available at:
https://www.uleth.ca/dspace/handle/10133/1220 (diakses 26 Februari 2014)
Price, Sylvia A. and Wilson, Lorraine M. 2006. Patofisiologi Konsep Klinis
Proses-proses Penyakit. Edisi 6. Jakarta:EGC. pp 472-484
R, Aden. 2010. Nutrisi Madu. Dalam : Aden, R. (ed). Manfaat dan Khasiat Madu,
Keajaiban Sang Arsitek Alam. Yogyakarta: Hanggar Kreator. P. 63-68.
Rahardhian,M., Mulyadi., Nurkhasanah. 2014. Efek Hepatoprotektor Ekstrak
Etanol Kelopak Bunga Rosella (Hibiscus sabdariffa L) Pada Tikus Spargue
Dawley yang diinduksi 7,12-Dimetilbenzaantrasen. Jurnal UAD hal:1-5.
Robbins, Stanley L, Kumar Vinay, and Cotran, Ramzi S.( 2011) Buku Ajar
Patologi. Edisi 7. Jakarta: EGC.
Rodwell VW, 2009. Katabolisme Protein dan Nitrogen Asam Amino. Biokimia
Harper Edisi 27, Jakarta, pp. 255-262.
Rohmatussolihat. 2009. Antioksidan, Penyelamat Sel-Sel Tubuh Manusia. Bio
Trends 4(1): 1-9.
Sadikin M, 2002, Biokimia Enzim, Widya Medika, Jakarta, pp. 280-309.
Sannigrahi, S., Upal, K., Dilip, K., Arijit, M., Souvik, R. 2009. Hepatoprotective
Potential of Flavonoid Rich Fraction of Enhydra Fluctuans Against CCL4-
Induced Oxidative Damage in Rats. Pharmacologyonline 2: 575-586.
Sarto, M. and Saragih, H. (2009). Penentuan Toksisitas Sub kronik Trombo
Propolis Pada Mencit (Mus Musculus L) Balb-C Jantan. Laboratorium
Penelitian dan Pengujian Terpadu . Yogyakarta: Fakultas Biologi
Universitas Gajah Mada.
Sarto, M. dan Saragih, H. 2009. Penentuan Toksisitas Sub kronik Trombo
Propolis Pada Mencit (Mus Musculus L) Balb-C Jantan. Laboratorium
Penelitian dan Pengujian Terpadu . Fakultas Biologi Universitas Gajah
Mada. Yogyakarta.
Sarwono, B. 2001. Kiat Mengatasi Permasalahan Praktis Lebah Madu.
Tangerang: Agromedia Pustaka.
Sen, S., Chakraborty, R., dan Sridar, C. 2010. Free Radicals, Antioxidants,
Diseases and Phytomedicines: Current Status and Future Prospect.
International Journal of Pharmaceutical Sciences Review and Research 3(1)
: 91-100.
Sforcin, Jose Mauricio. and Bankova, Vassya. (2011) „Propolis: Is there a
potential for the development of new drugs?‟ Journal of
Ethnopharmacology, 133(2011): 253-260.
xx
Sherlock S, Dooley J, 2002, Drugs and The Liver in Diseases of Liver and Biliary
System 11th ed., Blackwell Scientific Publications, Oxford, pp. 322-356.
Sisa, Miroslav.Bonnet, Susan L. and Ferreira, Daneel. (2010) „Photochemistry of
Flavonoids‟. Molecules, 2010 (15): 5196-5245.
Slavov, A., Trifonov, A., dan Peychev, L. 2013. Biologically Active Compounds
with Antitumor Activity in Propolis Extracts from Different Geographic
Regions. Biotechnol & Biotechnol 27(4): 4010-4013.
Snell, Richard S. 2006. Anatomi Klinik. Edisi 6. Jakarta:EGC. pp 240-246
Sugrani Andis dan Resi Agestia Waji. 2009. Makalah Kimia Organik Bahan Alam
Flavonoid(Quercetin). Makassar. Fakultas MIPA Universitas Hasanuddin.
Suranto A. 2004. Khasiat dan Manfaat Madu Herbal. Tangerang: Agromedia
Pustaka.
Syamsudin., W, Sudjaswadi., S,Partomuan., and L, Wan.2009. Chemical
Composition of Propolis from Different Regions in Java and their
Cytotoxic Activity. American Journal of Biochemistry ang Biotechnology 5
(4):180-183.
Tappi, E. S., L. Poppy, dan Loho, L. L. 2013. Gambaran Histopatologi Hati Tikus
Wistar yang diberikan Jus Tomat (Solanum Lycopersicum) Pasca
Kerusakan Hati Wistar ang Diinduksi Karbon Tetraklorida (CCL4). Jurnal e-
Biomedik,1(3).
http://ejournal.unsrat.ac.id/index.php/ebiomedik/article/view/3583/3111 22
Februari 2014 (11.48).
Tellingen, CV, 2003, Organ physiology from phenomenological point of view,
LouisBolkInstituut,Driebergen,
http://www.louisbolk.org/downloads/1295.pdf
The National Honey Board. 2004. Honey Health and Therapeutic Qualities.
http://www.nhb.org/download/factsht/compendium.pdf(15 Januari 2009)
Tirtawinata T. C. 2006. Makanan dalam Perspektif Al Quran dan Ilmu Gizi.
Jakarta: Balai Penerbit FK UI, pp:178-180.
Toreti, Viviane Cristina. et al, 2013. ‘Recent Progress of Propolis for Its
Biological and Chemical Compositions and Its Botanical Origin’. Evidence-
Based Complementary and Alternative Medicine, 2013. Available at:
http://www.hindawi.com/ (diakses 24 Februari 2014).
United States. Department of Health and Human Services .2005. Toxicological
Profile for Carbon Tetrachloride. Atlanta, Georgia: Division of Toxicology.
Availabla at: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=196&tid=35
(diakses 22 Februari 2014).
xxi
Wagh, Vijay. and Borkar, Rameshward. 2012. ‘Indian Propolis: a Potential
Natural Antimicrobial and Antifungal Agent’. International Journal of
Pharmacy and Pharmaceutical Sciences, 4(4): 12-17.
Winarsi, Heri. 2007. Antioksidan Alami dan Radikal Bebas, Potensi dan
Aplikasinya dalam Kesehatan. Yogyakarta: Kanisius.
World Health Organization. 2004. Carbon Tetrachloride in Drinking Water.
http://www.who.int/water_sanitation_health/dwq/chemicals/carbontetrachlo
ride.pdf 22 Februari 2014 (11.45).
Yildiz, O., C. Zehra., and S. Ozlem. 2013. Hepatoprotective Potential of Chestnut
Bee Pollen on Carbon Tetrachloride-Induced Hepatic Damages in Rats.
Evidence-Based Complementary and Alternative Medicine 2013: 1-9.
Zowail, M., Waer Hanna F,M., san Eltahawy, N,A,2012. Curative Effect of Bone
Marrow Cells Transplantation and/or Low Dose Gamma Irradiation on
Liver Injuries Induced by Carbon Tetrachloride. The Egyption Journal of
Hospital Medicine 46: 96-114.