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
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 ii
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
iii
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
iv
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.
v
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
vi
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 masingmasing 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
vii
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
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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 ix
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
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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
xi
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
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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
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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
xiv
DAFTAR LAMPIRAN
Lampiran 1: Data Hasil Penelitian ................................................................... 67 Lampiran 2: Analisis Data ............................................................................... 68 Lampiran 3: Dokumentasi Kegiatan ................................................................ 76 Lampiran 4: Surat keterangan penelitian ......................................................... 78
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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.
xvi
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): 295311. Galal, Reem M. 2012 ‘Potential Protective Effect of Honey Against Paracetamolinduced Hepatotoxicity’. Potential Protective Effect of Honey, 15 (1) : 674680. 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.
xvii
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.
xviii
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 CCL4Induced 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.
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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 eBiomedik,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’. EvidenceBased 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).
xx
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.
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