KARYA TULIS AKHIR PERBANDINGAN EFEKTIVITAS …eprints.umm.ac.id/25910/1/jiptummpp-gdl-wulandewif-37589-1...karya tulis akhir perbandingan efektivitas ekstrak propolis dan madu sebagai

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.