KARYA TULIS AKHIR
PENGARUH EKSTRAK BIJI ANGGUR (Vitis vinifera) VAR Alphonso Lavallee TERHADAP FUNGSI GINJAL MENCIT JANTAN (Mus musculus)
MODEL HIPERURISEMIA
Oleh Mira Wiji Lestari 201310330311100
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG 2017
KATA PENGANTAR
Assalamu‟alaikum Warahmatullah Wabarakatuh
Puji syukur kehadirat Allah SWT yang Maha Pengasih lagi Maha Penyayang karena atas rahmat dan hidayah-Nya penulis dapat menyelesaikan karya tulis akhir ini dengan baik. Shalawat serta salam selalu tercurahkan kepada Rasulullah Muhammad SAW, keluarga dan para sahabat yang telah berjasa membawa syiar dakwah Islam keseluruh dunia.
Penelitian tugas akhir ini berjudul “Pengaruh Ekstrak Biji Anggur (Vitis
vinifera) var Alphonso lavellee Terhadap Ginjal Mencit Jantan (Mus musculus)
Model Hiperurisemia” diajukan untuk memenuhi persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas Muhammadiyah Malang.
Penulis menyadari bila tugas akhir ini masih jauh dari kata sempurna, oleh karena itu, penulis membuka diri untuk segala saran dan kritik yang bersifat membangun guna kesempurnaan dari karya tulis akhir ini. Semoga karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi semua pihak.
Wassalamu‟alaikum Warahmatullah Wabarakatuh
Malang, Februari 2017
DAFTAR ISI
HALAMAN JUDUL ... i
LEMBAR PENGESAHAN ... ii
PERNYATAAN ORISINALITAS ... iii
LEMBAR PENGUJIAN ... iv KATA PENGANTAR ... v UCAPAN TERIMAKASIH ... vi ABSTRAK ... viii ABSTRACT ... ix DAFTAR ISI ... x
DAFTAR TABEL ... xiv
DAFTAR GAMBAR ... xv
DAFTAR SINGKATAN ... xvi
DAFTAR LAMPIRAN ... xvii
BAB 1 PENDAHULUAN ... 1 1.1 Latar Belakang ... 1 1.2 Rumusan Masalah ... 3 1.3 Tujuan Penelitian ... 3 1.3.1 Tujuan umum ... 3 1.3.2 Tujuan khusus ... 3 1.4 Manfaat Penelitian ... 3
BAB 2 TINJAUAN PUSTAKA ... 5
2.1.1 Definisi ... 5
2.1.2 Metabolisme Asam Urat ... 6
2.2 Asam Urat dan Hubungannya dengan Disfungsi Ginjal ... 8
2.3 Induksi Hiperurisemia ... 15
2.4 Tanaman Anggur (Vitis vinivera) ... 16
2.4.1 Taksonomi ... 16
2.4.2 Deskripsi tanaman anggur ... 16
2.4.3 Kandungan, manfaat, dan kelebihan biji anggur ... 17
2.4.4 Deskripsi tanaman anggur varietas Alphonso lavallee ... 21
2.5 Mencit ... 23
2.6 Kreatinin ... 26
BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS PENELITIAN ... 28
3.1 Kerangka Konseptual Penelitian ... 28
3.2 Hipotesis Peneliti ... 30
BAB 4 METODE PENELITIAN ... 31
4.1 Jenis dan Rancangan Penelitian ... 31
4.2 Lokasi dan Waktu Penelitian ... 31
4.3 Populasi dan Sampel ... 31
4.3.1 Populasi ... 31
4.3.2 Sampel ... 31
4.3.4 Teknik pengambilan sampel ... 33
4.4 Karakteristik sampel penelitian ... 33
4.5 Variabel penelitian ... 34
4.6 Definisi Operasional ... 34
4.7 Alat dan Bahan Penelitian ... 35
4.8 Prosedur Penelitian ... 36
4.8.1 Dasar penentuan dosis ... 36
4.8.2 Pembagian kelompok tikus ... 37
4.8.3 Adaptasi hewan percobaan ... 38
4.8.4 Pemberian kalium oksonat ... 38
4.8.5 Pembuatan ekstrak biji anggur ... 38
4.8.6 Pemberian ekstrak biji anggur ... 39
4.8.7 Proses anastesi dan pengambilan sampel darah ... 39
4.8.8 Pengukuran kadar serum ureum dan kreatinin ... 40
4.9 Alur Penelitian ... 41
4.10 Analisis Data ... 42
4.11 Jadwal Penelitian ... 43
BAB 5 HASIL PENELITIAN DAN ANALISIS DATA ... 44
5.1 Hasil Penelitian ... 44
5.2 Analisis Data ... 45
5.2.2 Uji One way ANOVA ... 45
5.2.3 Uji Post hoc (Bonferroni) ... 46
5.2.4 Uji Regresi Linier... 46
BAB 6 PEMBAHASAN ... 48
BAB 7 KESIMPULAN DAN SARAN ... 55
7.1 Kesimpulan ... 55
7.2 Saran ... 55
DAFTAR LAMPIRAN
Lampiran Halaman
1. Hasil penelitian kadar kreatinin serum mencit ... 61
2. Analisis data ... 62
3. Dokumentasi penelitian ... 68
4. Surat determinasi tanaman ... 70
5. Surat kelayakan etik ... 71
DAFTAR PUSTAKA
Bao L, Zhang Z, Dai X, et al. 2015,‟Effects of Grape Seed Proanthocyanidin
Extracts on Renal Injury in Type 2 Diabetic Rats‟, Molecular Medicine Report, 11, 645-652
Baydar NG, Ozkan G, dan Sagdic O, 2004,’Total Phenolic Contents and
Antibacterial Activities on Grape (Vitis vinifera L) extracts‟, Food Control,
15, 335-339
Beaumont R, 2009,‟Research Methods and Experimental Design‟,Introduction to
Health Informatics
Bedell MA, Largaespada DA, Jenkins NA, et al. 1997,‟Mouse Model of Human
Disease Part II: Recent Progress and Future Direction‟, Genes and Development, 11 , 11-43
Bozan B, Tosun G, Ozcan D, 2008,‟Study of Polyphenol Content in The Seeds of
Red Grape (Vitis vinifera L.) Varieties Cultivated in Turkey and Their Antiradical Activity‟, Food Chemistry, 109 , 426-430
Bradford A, 2014,‟ Mouse facts : Habits, Habitat, and Types of Mice
Breyer MD, Qi Z, 2010,‟Better Nephrology for Mice and Man‟, Kidney
International, 77, 487-489
Busuioc M, Voroneanu L, Hogas S, et al. 2007,‟Pathogenic Impact of
Hyperuricemia in Renal and Cardiovascular Disease‟, BANTAO journal,
5(1),1
Charalambous G, 1995, Food Flavors : Generation, Analysis, and Process
Influence, Elsevier, Amsterdam
Charan J, Kantharia ND, 2013.‟How to Calculate Sample Size in Animal
Study?’Journal of Pharmacology and Pharmacotherapeutics, 4(4),303-306
Chen YS, Hu QH, Zhang X, et al. 2013,’Beneficial Effect on Rutin on
Oxonate-Induced Hyperuricemia and Renal Dysfunction in Mice‟, Pharmacology,
92, 75-83
Cui X, Liu X, Feng H, et al. 2012,‟Grape Seed Proanthocyanidin Extracts
Enhance Endothelial Nitric Oxide Synthase Expression Through 5’-AMP Activated Protein Kinase/Surtuin 1-Krupple Like Factor 2 Pathway and Modulate Blood Pressure in Ouabain Induced Hypertensive Rats‟, The Pharmaceutical Society of Japan, 35(12), 2192-2197
David, Arkeman H, 2008, „Evaluation Of The Oral Toxicity Of Formaldehyde In
Dementrius L, 2005,‟ Of Mice and Man‟, European Molecular Biology
Organization, 6
Dunn SR, Qi Z, Bottinger EP, 2004,‟ Utility of Endogenous Creatinine Clearance
As a Measure of Renal Function in Mice‟, Kidney International, 65, 1959 -
1967
Elagamay AA, Abdel-Wahab MA, Shimaa MME, et al. 2013,‟Comparative Study
of Morphological Characteristics and Chemical Constituents for Seeds of Some Grape Table Varieties‟, Journal of American Science, 9(1)
Filiopoulos V, Hadjiyannakos D, Vlassopoulos D, 2011,‟New Insights into Uric
Acid Effects on the Progression and Prognosis of Chronic Kidney Disease‟, CIN
Fine AM, 2000,‟Oligomeric Proanthocyanidin Complexes: History, Structure,
and Phytopharmaceutical Applications‟, Alternative Medicine Review,
5(2), 144-151
Georgiev V, Ananga A, Tsolova Violeta, 2014,‟Recent Advances and Uses of
Grapes Flavonoids as Nutraceuticals‟, Open Access Nutrients, 6, 391-415
Godevac D, Tesevic V, Velickovic M, et al. 2010,‟Poliphenolic Compounds in
Seeds From Some Grape Cultivars Grow in Serbia‟, Journal of the Serbian Chemical Society, 75 (12), 1641-1652
Haidari F, Rashidi MR, Keshavarz SA, et al, 2008,‟Effects of Onion on Serum
Uric Acid Levels and Hepatic Xanthine Dehydrogenase / Xanthine Oxidase Activities in Hyperuricemia Rats‟, Pakistan Journal of Biological Science,
11(14), 1779-1784
Hashemi M, et al. 2012,‟ Effect of grape seed extract on renal ischaemic
reperfusion in Rats’,Journal of Animal and Veterinary Advance, vol 11
(14), 2529- 2532
Hussein S, Abdrabba S, 2015,‟Physico-chemical Characteristics, Fatty Acid,
Composition of Grape Seed Oil and Phenolic Compounds of Whole Seeds, Seeds and Leaves of Red Grape in Libya‟, International Journal of Applied Science and Mathematics, vol.2, issue 5, 2394-2894
Ichida K, Matsuo H, Takada T, et al. 2012,‟Decrease Extra Renal Urate
Excretion is a Common Cause of Hyperuricemia‟, Nature Communications, 3(764)
Iseki K, Oshiro S, Tozawa M, et al. 2001,‟Significance of Hyperuricemia on the
Early Detection of Renal Failure in a Cohort of Screened Subjects‟, Hypertensive Research, 24(6), 691-697
James GF, Barthold SW, Davisson MT, et al. 2007, The Mouse in Biomedical
Research 2nd edition vol 3,Elsivier, USA
Johnson RJ, Nakagawa T, Jalal D, et al. 2013,‟Uric acid and Chronic Kidney
Disease : Which is Chasing Which?,‟ Nephrology Dialysis Transplantation
Kang DH, Nakagawa T, 2005,‟Uric Acid and Chronic Renal Disease: Possible
Implication of Hyperuricemia on Progression of Renal Disease‟, Research Gate
Khosla UM, Zharikov S, Finch JL, et al. 2005,‟Hyperuricemia Induces
Endothelial Dysfunction‟, International Society of Nephrology, 67,
1739-1742
Kutzing MK, Firestein BL, 2007,‟Altered Uric Acid Levels and Disease States‟,
The Journal of Pharmacology And Experimental Therapeutic, 324(1)
Limtrakul P, Yodkeeree S, Pitchakarn P, et al. 2016,‟Antiinflammatory Effects of
Proanthocyanidin-rich Red Rice Extract Via Suppression of MAPK, AP-1 and NF-κB Pathways in Raw 264.7 Macrophages‟, Nutrition Research and Practice, 10(3), 251-258
Madiyono B, Moeslichan Mz S, Sastroasmoro S, Budiman I dan Purwanto H, 2014,‟Dasar-dasar Metodologi Penelitian Klinis‟, Edisi 5, Sagung Seto, Jakarta, 352-386
Mc Gill, 2009,‟Laboratory Animal Biomethodology Workshop‟, Animal Care
Committee
Marcel I, nd,‟ Mouse Biomethodology‟, Laboratory Animal Resource Center The University of Texas
Merriman TR, 2015,‟An Update on the Genetic Architecture of Hyperuricemia
and Gout‟,Arthritis Research and Therapy, 17, 98
Nile SH, SH Kim, Ko EY, et al. 2013,‟ Polyphenolic Contents and Antioxidant
Properties of Different Grape (V. vinifera, V. labrusca, and V. hybrid) Cultivar‟, Biomed Research International
Prasad Sah OS, Qing YX, 2015,‟Associations Between Hyperuricemia and
Chronic Kidney Disease : A Review,‟ Nephrology and Urology Reseach Center, 7(3), e27233
Rodrigues WF, Miguel CB, Napimoha MH, et al. 2014,‟ Establishing Standards
for Studying Renal Function in Mice Through Measurements of Body Size Adjusted Creatinine and Urea Levels‟, Biomed Research International,
Rosenthal N, Brown S, 2007,‟The Mouse Ascending: Perspective for Human
Disease Models‟, Nature Cell Biology, 9(9)
Rukmana HR, 2008, Bertanam Buah-Buahan di Pekarangan, Kanisius, Yogyakarta
Sanchez Lozada LG, Soto V, Tapia E, et al. 2008,‟Role of Oxidative Stress in the
Renal Abnormalities Induces by Experimental Hyperuricemia‟, American Journal od Physiology : Renal Physiology, 295(4), F1134-F1141
Schwarz R, Kaspar A, Seelig J, et al. 2002,‟Gastrointestinal Transit Time in Mice
and Humans Measured with 27Al and 19F Nuclear Magnetiv Resonance’, Magnetic Resonance in Medicine, 48, 255-261
Shi YW, Wang CP, Lie L, et al. 2012,‟Antihyperuricemic and Nephroprotective
Effects of Resveratrol and its Analogues in Hyperuricemic Mice‟, Molecular Nutrient Food Research, 1-12
Smith E, Marshal L, 2015,‟Global Prevalence of Hyperuricemia: A Systematic
Review of Population-Based Epidemiological Studies‟, American College of Rheumatology, 2236
So Alexander, Thorens B, 2010,‟Uric Acid Transport and Disease‟, Science in
Medicine, 120(6), 1791-1799
Soltani Z, Rasheed K, Kapusta DR, et al. 2013,‟Potential Role of Uric Acid in
Metabolic Syndrome, Hypertension, Kidney Injury, and Cardiovascular Diseases : Is it Time for Reappraisal?‟, Curr Hypertems Rep, 15(3),
175-181
Susic D, Frohlich ED, 2015,‟Hyperuricemia: A Biomarker of Renal
Hemodynamic Impairment‟, Cardiorenal Medicine, 5, 175-182
Viazzi F, Leoncini G, Pontremoli R, 2011,‟Cardiovascular and Renal Effects of
Hyperuricaemia and Gout‟, Reumatismo, 64(4), 253-262
Wang R, MA Chun H, Zhou F, et al.2016,‟Siwu Decoction Attenuates
Oxonate-Induced Hyperuicemia and Kidney Inflammation in Mice‟, Chinese Journal of Natural Medicine, 14(7), 0499-0507
Wyss M, Kaddurah-daouk, 2000,‟Creatine and Creatinine Metabolism‟,
Physiological Review, 80(3)
Xia EQ, Deng GF, Guo YJ, et al. 2010,‟Biological Activities of Poliphenols From
Zhou B, Chen T, Liu C, et al. 2014,‟IL-1β is Related to Hyperuricemic Nephropathy Induced by High-Purine Diet‟, Gout and Hyperuricemia,