KARYA TULIS AKHIR

EFEK EKSTRAK BUAH NAGA MERAH (Hylocereus polyrhizus)

TERHADAP PERUBAHAN HISTOPATOLOGI TUBULUS PROKSIMAL

GINJAL PADA TIKUS PUTIH STRAIN WINSTAR YANG DIINDUKSI

MINYAK KELAPA SAWIT PEMANASAN BERULANG

Oleh:

PUTRI MEILISSA AJENG PERMATA SARI

201210330311157

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2016

ii

HASIL PENELITIAN

EFEK EKSTRAK BUAH NAGA MERAH (Hylocereus polyrhizus)

TERHADAP PERUBAHAN HISTOPATOLOGI TUBULUS PROKSIMAL

GINJAL TIKUS PUTIH STRAIN WISTAR YANG DIINDUKSI MINYAK

KELAPA SAWIT PEMANASAN BERULANG

KARYA TULIS AKHIR

Diajukan Kepada

Universitas Muhammadiyah Malang

untuk Memenuhi Salah Satu Persyaratan

dalam Menyelesaikan Program Sarjana

Fakultas Kedokteran

Oleh:

PUTRI MEILISSA AJENG PERMATA SARI

201210330311157

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2016

iii

iv

v

KATA PENGANTAR

Syukur Alhamdulillah saya panjatkan kepada Allah SWT atas rahmat dan

hidayah-Nya sehingga penulis dapat menyelesaikan tugas akhir yang berjudul Efek

Ekstrak Buah Naga Merah (Hylocereus polyrhizus) Terhadap Perubahan

Histopatologi Tubulus Proksimal Tikus Putih Strain Wistar Yang Diinduksi

Minyak Kelapa Sawit Pemanasan Berulang. Penulisan penelitian ini dilakukan

dalam rangka memenuhi salah satu syarat untuk mencapai gelar Sarjana

Kedokteran Jurusan Pendidikan Dokter pada Fakultas Kedokteran Universitas

Muhammadiyah Malang. Pada kesempatan ini perkenankanlah penulis

menyampaikan penghargaan dan terima kasih kepada:

1. dr. Desy Andari, M.Biomed selaku selaku Pembimbing I atas bimbingan,

ketelitian, perhatian, dukungan, motivasi, saran dan bantuan yang telah

diberikan dalam penyusunan karya tulis akhir ini.

2. dr. Andhika Maharani selaku selaku Pembimbing II atas bimbingan,

ketelitian, perhatian, dukungan, motivasi, saran dan bantuan yang telah

diberikan dalam penyusunan karya tulis akhir ini.

3. dr. Halida Nelasari, Sp.OG selaku penguji yang telah memberikan saran,

kritik, bimbingan dan motivasi yang membangun selama saya

menyelesaikan skripsi ini.

4. dr. Soebarkah Basuki, Sp.PA yang telah membantu pembacaan preparat

hepar untuk karya tulis akhir ini.

5. Mamaku Suparmi, SE dan ayahku Juni Wibowo tercinta yang yang selama

ini telah memberikan segala kasih sayang, dukungan, materi, menjadi

vi

motivator terbesar untuk menjalani kuliah dari awal pendidikan hingga

penyelesaian skripsi ini dan senantiasa mendoakan penulis.

6. Adik-adikku tercinta Danzen Junami Wibowo dan Tiara Tri Indah Sari yang

telah memberi doa, motivasi, dan bantuan dalam bentuk apapun selama

pendidikan hingga penyelesain skripsi ini.

7. Teman-temanku tersayang SSSH: Debby Rosyida, Hillda WP, Rahma F,

Intan Putri, Veronica Y, Fatin Chaydar, Asri Anin, Destra Putri, Afina F,

dan Tanty Tunjung yang tanpa henti memberi motivasi, saran, dan banyak

mendampingi selama pendidikan hingga penyelesian skripsi ini.

8. Teman sepenelitian Debby Rosyida, Dito Sakti dan Adhi Candra yang

selama penelitian telah banyak membantu, memberi semangat dan saran

selama penelitian berlangsung hingga penyelesaian skripsi ini.

9. Rekan sejawat lainnya yang telah memberikan dorongan dan bantuan dari

awal hingga akhir penyelesaian skripsi ini yang tidak bisa disebutkan satu-

persatu.

Penulis menyadari bahwa penyusunan tugas akhir ini jauh dari sempurna,

walaupun demikian penulis telah berusaha semaksimal, maka dari itu penulis ingin

menyampaikan permohonan maaf jika masih terdapat kekurangan dalam skripsi ini.

Akhir kata penulis berharap adanya saran dan kritik yang membangun dan semoga

penelitian ini dapat menambah wawasan serta bermanfaat bagi semua pihak.

Malang, 10 Agustus 2016

Penulis

vii

DAFTAR ISI

Halaman

HALAMAN JUDUL ............................................................................................. i

PENGESAHAN LAPORAN HASIL PENELITIAN ....................................... iii

LEMBAR PENGUJI ........................................................................................... iv

KATA PENGANTAR .......................................................................................... v

ABSTRAK

ABSTRACT

DAFTAR ISI ....................................................................................................... vii

DAFTAR TABEL .............................................................................................. x

DAFTAR GAMBAR.......................................................................................... xi

DAFTAR SINGKATAN ................................................................................... xii

DAFTAR LAMPIRAN ..................................................................................... xiii

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 ............................................................................... 4

1.4.1 Manfaat Teoritis .................................................................... 4

1.4.2 Manfaat Aplikatif .................................................................. 4

BAB 2 TINJAUAN PUSTAKA ........................................................................... 5

2.1 Ginjal .................................................................................................... 5

2.1.1 Anatomi Ginjal .......................................................................5

2.1.2 Histologi Ginjal …................................................................. 6

2.1.3 Fisiologi Ginjal ................................................................... 11

2.1.4 Kerusakan Ginjal ................................................................. 12

2.1.5 Mikroskopis Kerusakan Ginjal ........................................... 14

2.1.6 Pengaruh Profil Lipid Terhadap Kerusakan Ginjal ........................... 16

viii

2.2 Tikus Putih Jantan (Rattus Norvegicus Strain Winstar) ...................... 17

2.2.1 Perbandingan Ginjal Tikus dan Manusia .............................. 18

2.2.2 Fisiologi Ginjal Tikus ........................................................... 21

2.3 Buah Naga Merah (Hylocereus polyrhizus) ....................................... 22

2.3.1 Senyawa Antioksidan dalam Buah Naga Merah ................. 25

2.4 Oksidan – Antioksidan ....................................................................... 31

2.4.1 Oksidan ............................................................................... 32

2.4.2 Antioksidan ......................................................................... 33

2.5 Mekanisme Flavonoid untuk Mencegah Kerusakan Ginjal ............... 37

BAB 3 KERANGKA KONSEP ......................................................................... 39

3.1 Kerangka Konsep ............................................................................... 39

3.2 Hipotesis ............................................................................................. 41

BAB 4 METODE PENELITIAN ...................................................................... 42

4.1 Rancangan Penelitian ......................................................................... 42

4.2 Lokasi dan Waktu Penelitian ............................................................. 42

4.3 Populasi dan Sampel .......................................................................... 42

4.3.1 Populasi ............................................................................... 42

4.3.2 Sampel ................................................................................. 42

4.3.3 Teknik Sampling ................................................................. 42

4.3.4 Estimasi Besar Sampel ........................................................ 43

4.3.5 Karakter Sampel Penelitian ................................................. 44

4.3.6 Variabel Penelitian .............................................................. 44

4.3.6.1 Variabel Bebas ..................................................... 44

4.3.6.2 Variabel Tergantung ............................................. 44

4.3.7 Definisi Operasional Variabel ............................................. 44

4.4 Dasar Penentuan Dosis ....................................................................... 45

4.5 Bahan dan Instrumen Penelitian ......................................................... 46

4.5.1 Pembuatan Ekstrak Buah Naga Merah ............................... 46

4.5.2 Pembuatan Minyak Kelapa Sawit Pemanasan Berulang..... 47

4.5.3 Pembedahan Tikus .............................................................. 47

4.6 Alur Penelitian ................................................................................... 48

4.7 Prosedur Penelitian ............................................................................. 50

ix

4.7.1 Pembagian Kelompok Tikus ............................................... 50

4.7.2 Adaptasi ............................................................................... 50

4.7.3 Pemberian Minyak Kelapa Sawit Pemanasan Berulang ..... 51

4.7.4 Pemberian Ekstrak Buah Naga Merah ............................... 51

4.7.5 Proses Anastesi dan Pembedahan Hewan Coba ................. 51

4.7.5.1 Proses Anastesi .................................................... 51

4.7.5.2 Proses Pembedahan ............................................. 52

4.7.6 Proses Pembuatan Preparat Histologi ................................. 52

4.8 Analisis Data ...................................................................................... 52

BAB 5 HASIL PENELITIAN DAN ANALISA DATA .................................. 54

5.1 Hasil Penelitian .................................................................................. 54

5.2 Analisa Data ....................................................................................... 56

BAB 6 PEMBAHASAN ..................................................................................... 57

BAB 7 KESIMPULAN DAN SARAN .............................................................. 64

7.1 Kesimpulan ....................................................................................... 64

7.2 Saran .................................................................................................. 65

DAFTAR PUSTAKA ......................................................................................... 66

LAMPIRAN ........................................................................................................ 74

x

DAFTAR TABEL

Halaman

2.1 Perbedaan antara ginjal manusia dan tikus..................................................... 20

2.2 Kandungan Zat Gizi Buah Naga Merah per 100 gram ................................. 24

2.3 Kandungan Zat Antioksidan Buah Naga ...................................................... 26

2.4 Konsentrasi Betasianin Buah Naga Merah (Hylocereus polyrhizus) ........... 28

2.5 Konsentrasi EC50 dan anti-radical scavenger dari buah (kulit dan daging

buah) dan daging buah H. polyrhizus dan H. undatus.................................... 29

2.6 Kandungan Asam Askorbat (Vitamin C) dari buah (kulit dan daging buah)

dan daging buah H. polyrhizus dan H. undatus ............................................. 30

5.1 Hasil Uji Analisis Statistik Tukey .................................................................. 56

xi

DAFTAR GAMBAR

Halaman

2.1 Struktur Anatomis Ginjal .............................................................................. 5

2.2 Struktur Mikroskopik Ginjal .......................................................................... 7

2.3 Perubahan Histologis Ginjal Tikus Jantan yang Mengalami Nekrosis ......... 15

2.4 Struktur Histologis Ginjal Tikus ................................................................... 19

2.5 Struktur Histologis Ginjal Manusia ............................................................... 19

2.6 Pewarnaan PAS tubulus proksimal dan tubulus distal ................................... 19

2.7 Tanaman Buah Naga ..................................................................................... 21

2.8 Buah Naga Merah (Hylocereus polyrhizus) .................................................. 23

2.9 Kerangka C6-C3-C6 Flavonoid ..................................................................... 28

2.9 Scavenging of ROS (Ro) by Flavonoid .......................................................... 29

3.1 Skema Langkah – Langkah Penelitian ........................................................... 49

5.1 Preparat Ginjal Perbesaran 400x .................................................................... 54

5.2 Grafil Rata-rata Sel Tubulus Proksimal ......................................................... 55

5.3 Grafik Hasil Uji Regresi Linier ...................................................................... 57

xii

DAFTAR SINGKATAN

µm : Mikrometer

BB : Berat badan

CE : Catechin equivalents

cm : Sentimeter

DNA : Deoxyribonucleic acid

EC50 : Efficient concentration

GAE : Gallic Acid Equivalents

HDL : High Density Lipoproteins

HE : Hematosiklin Eosin

IL-2 : Interleukin-2

LDL : Low Density Lipoproteins

mg : Miligram

ml : Mililiter

mm : Milimeter

PAS : Periodic Acid Schiff

ppm : part per million

ROS : Reactive Oxygen Species

S.D : Sprague-Dawley

SOD : Superoxide dismutase

TE : Trolox equivalents

TG : Trigliserida

TNF-α : Tumor Necrosis Factor Alpha

xiii

DAFTAR LAMPIRAN

Halaman

Lampiran 1. Data Hasil Pengamatan Histopatologi ........................................ 74

Lampiran 2. Analisis Data Penelitian .............................................................. 75

Lampiran 3. Dokumentasi Penelitian ............................................................... 78

Lampiran 4. Surat Keterangan Pembacaan PA. ............................................... 81

Lampiran 5. Surat Keterangan Pembuatan Preparat …............................... 82

Lampiran 6. Surat Keterangan Telah Melakukan Penelitian ...................... 83

Lampiran 7. Surat Laik Etik ....................................................................... 84

Lampiran 8. Kartu Konsultasi Tugas Akhir ............................................... 85

xiv

DAFTAR PUSTAKA

Abdelwahab IS, Mohan S, Elhassan MM, et al., 2011, Antiapoptotic and

Antioxidant Properties of Orthosiphon stamineus Benth (Cat’s Whiskers),

Evidence-Based Complementary and Alternative Medicine, vol. 2011, pp.

5-6.

Acharya JK, Dasgupta U, Rawat SS, et al., 2008, Cell-nonautonomous Function of

Ceramidase in Photoreceptor Homeostasis, Neuron 57, vol. 1, pp. 69-79.

Agati G, Azzarello E, Pollastri S, et al., 2012, Flavonoids as Antioxidants in Plants:

Location and Functional Significance, Journal Plant Science, vol. 196, pp.

67-76.

Alpers CE and Fogo AB, 2007, Ginjal dan Sistem Urinarius, In: Kumar V, Cotran

RS, Robbins SL (eds), Buku Ajar Patologi Robbins Volume 1, Edisi VII,

EGC, Jakarta, pp. 186.

Armitage D, 2008, Rattus Norvegicus, University of Machigan, viewed 23 Maret

2016,<http://animaldiversity.ummz.umich.edu/site/accounts/informations/

Rattus_norvegicus.html>.

Asni E, Ismawati, Arlem BV, 2014, Durasi Konsumsi Makanan Digoreng Dengan

Minyak Kelapa Sawit Pemanasan Berulang Terhadap Malondialdehid

Plasma, MKA, Vol. 37 No. 1.

Awney HA, Massoud M, 2011, In Vivo Evaluation of Oxidative Stress Biomarkers

in Young Male Rats Exposed to Long Term Stevioside Feeding, The FASEB

Journal, vol. 25, Department of Environmental Studies, Institute of

Graduate Studies and Research, Alexandria University, Alexandria, Egypt.

Belinha I, Amorim M A, Rodrigues P, et al., 2007, Quercetin Increases Oxidative

Stress Resistance and Longevity in Saccharomyces Cerevisiae, Journal of

Agricultural and Food Chemistry, Vol. 55, pp. 2446-2451.

Birben E, Sahiner MU, Sackesen C, et al., 2012, Oxidative Stress and Antioxidant

Defense, World Allergy Organization Journal, vol. 5, pp. 9-19.

Bhagaskara, Liana P, Santoso B, 2015, Hubungan Kadar Lipid dengan Kadar

Ureum & Kreatinin Pasien Penyakit Ginjal Kronik di RSUP Dr.

Mohammad Hoesin Palembang, Jurnal Kedokteran dan Kesehatan,

palembang, vol.2 no.2, pp. 7.

Cahyono B, 2009, Sukses Bertanam Buah Naga, Pustaka Mina, Jakarta, pp. 14-16.

Cai Y, Sun M, Corke H, 2003, Antioxidant Activity of Betalains from Plants of The

Amaranthaceae, Journal of Agricultural and Food Chemistry, vol. 51, pp.

2288-2294.

xv

Choe E, Min BD, 2006, Mechanisms and Factors for Edible Oil Oxidation,

Comprehensive Reviews in Food Science and Food Safety, vol. 5 issue 4,

pp. 169–186.

Choo SW, Yong KW, 2011, Antioxidant Properties of Two Species of Hylocereus

Fruits, Pelagia Research Library, vol.2 (3), pp. 418-425

Connor E, 2012, Best of Histology, Biology Department, University of

Massachusetts Amherst, Massachusetts, USA, viewed 15 Juni 2015, <

http://bcrc.bio.umass.edu>.

DeHaven WI, Jones BF, Petranka JG, et al., TRPC channels function independently

of STIM1 and Orai1, The Journal of Physiology, vol. 587, pp. 2275–2298.

Djauhari T, Ilahika PA, 2014, Buku Ajar Anatomi Blok Uropoetika dan Reproduksi,

Departemen Anatomi FK UMM, Malang, pp. 29.

Eroschenko VP, 2013, Atlas Histologi diFiore dengan Korelasi Fungsional Edisi

11, EGC, Jakarta, pp. 325-333.

Eweka AO, Adjene JO, 2007, Histological Studies of the Effects of Monosodium

Glutamate on the Medial Geniculate Body of Adult Wister Rat, Electrone. J.

Biomed, vol. 2, pp. 9-13, viewed 20 Juni 2016, <

http://biomed.uninet.edu/2007/n2/eweka.html >

Faridah A, Holinesti R, Syukuri D, 2014, Identifikasi Pigmen Betasianin dari Kulit

Buah Naga Merah (Hylocereus polyrhizus), Fakutas Teknik Universitas

Negeri Padang, Padang, pp. 147-154.

Farikha IN, Anam C, Widowati E, 2013, Pengaruh Jenis dan Konsentrasi Bahan

Penstabil Alami Terhadap Karakteristik Fisikokimia Sari Buah Naga

Merah (Hylocereus polyrhizuz) Selama Penyimpanan, Jurnal Teknosains

Pangan, vol. 2 (1), pp. 31-38.

Gartner JP, Hiatt JL, 2007, Color Text Book of Histology 3th ed, Elsevier Saunders,

Philadelphia, pp 45-437.

Gupta MK, 2005, Edible Oil and Fat Products: Edible Oils, In: Shahidi (eds),

Bailey’s Industrial Oil and Fat Products, edisi 6, John Wiley & Sons Inc,

New Jersey, vol. 2, pp. 333-354.

Guyton AC, Hall JE, 2008, Buku Ajar Fisiologi Kedokteran, edisi ke-6, EGC,

Jakarta, pp. 324 – 33

Halliwell B, 2006, Reactive Species and Antioxidants. Redox Biology is a

Fundamental Theme of Aerobic Life, Update on Reactive Species and

xvi

Antioxidants, Department of Biochemistry, National University of

Singapore, Vol. 141, pp. 312-322.

Han MR, Zhang PJ, Skibsterd HL, 2012, Reaction Dynamics of Flavonoids and

Carotenoids as Antioxidants, Journal Molecules, Beijing, China, vol. 17, pp.

2140-2160.

Harivaindaran VK, Rebecca SPO, Chandran S, 2008, Study of Optimal

Temperature, pH and Stability of Dragon Fruit (Hylocereus polyrhizus)

Peel for use as Potential Natural Colorant, Pakistan Journal of Biological

Sciences, Kuala Lumpur, Malaysia, vol. 11, pp. 2259-2263.

Hinneburg I, Dorman D, Hiltunen R, 2006, Antioxidant Activities of Extracts from

Selected Culinary Herbs and Spices, Food Chemistry Journal, University of

Helsinki, Finland, vol. 97, pp. 122-129.

Hoyt FR, Hawkins VJ, Clair St, et al., 2007, Mouse Physiology, In: Fox GJ,

Barthold WS, Davisson TM, Newcomer EC, Quimby WF, SmithLA (eds),

The Mouse in Biomedical Research, 2nd Edition, American College of

Laboratory, USA, pp. 69-71, <

https://books.google.co.id/books?id=Gi6rIvx7Ni4C&pg=PA70&dq=renal

+physiology+in+mouse&hl=id&sa=X&ved=0ahUKEwix2fLV-

5LLAhWBWY4KHZuxAF0Q6AEIGTAA#v=onepage&q=renal%20physi

ology%20in%20mouse&f=false>.

Idawati Nurul, 2012, Budidaya Buah Naga Hitam Varietas Baru yang Kian Diburu,

Pustaka Baru Press, Yogyakarta, pp. 2-5.

Indriasari I, 2012, Ekstrak Ethanol Buah Naga Merah (Hylocereus polyrhizus)

Memperbaiki Profil Lipid pada Tikus Winstar Jantan (Rattus Norvegicus)

Dislipidemia, Tesis, Universitas Udayana, Denpasar.

Jamilah B, Shu CE, Kharidah M, et al., 2011, Physicochemical Characteristics of

Red Pitaya (Hylocereus polyrhizus) Peel, Journal of Agricultural Food

Chemistry, Selangor, Malaysia, vol. 18, pp. 279-286.

Junqueira LC, Carneiro J, 2007, Histologi Dasar Teks dan Atlas, Edisi 10, EGC,

Jakarta, pp. 334.

Jaarin K, Kamisah Y, 2012, Repeatedly Heated Vegetable Oils and Lipid

Peroxidation, INTECH, Chapter 10, pp. 212-228.

Katzung B, Susan B, Anthony J, 2013, Farmakokinetik dan Farmakodinamika:

Dosis Rasional dan Waktu Kerja Obat, In: Bicholas HG, Holford (eds),

Farmakologi Dasar dan Klinik, Edisi 12, Penerbit Buku Kedokteran EGC,

Jakarta, Hal. 41-43.

xvii

Khalili AM, A.B AC, A. Manaf AA, 2012, Total Antioxidant Activity, Total

Phenolic Content And Radical Scavenging Activity Both Flesh And Peel Of

Red Pitaya, White Pitaya And Papaya, International Journal of Pharmacy

and Pharmaceutical Sciences, Malaysia, vol. 4 (2), pp. 113-122.

Khan MR, Rizvi W, Khan GN, et al., 2009, Carbon Tetrachloride Induced

Nephrotoxicity in Rats: Protective role of Digera muricata, Journal of

Ethnopharmacology, Ismabul, Pakistan, vol. 122, pp. 91-99.

Kumalaningsih S, 2006, Antioksidan Alami, Trubus Agrisarana, Surabaya.

Kumar V, Cotran SR, Robins SL, 2007, Buku Ajar Patologi, edisi 7, vol. 2, EGC,

Jakarta,

Kuncahyo I, Sunardi, 2012, Uji Aktivitas Antioksidan Ekstrak Belimbing Wuluh

(Averrhoa bilimbi L.) Terhadap 1,1-diphenyl-2-picrylhidrazyl (DPPH),

Seminar Nasional Teknologi, Yogyakarta, pp. 1-9.

Madiyono B, dkk, 2014, Perkiraan Besar Sampel, In: Sastroasmoro Sudigdo,

Ismael Sofyan (eds), Dasar – Dasar Metodologi Penelitian Klinis, Edisi V,

Sagung Seto, Jakarta, pp. 381.

Mahattanatawee K, Manthey JA, Luzio G, et al., 2006, Total Antioxidant Activity

and Fiber Content of Select Florida-Grown Tropical Fruits, Journal Of

Agricultural and Food Industry, Florida, vol. 54 no. 19, pp. 7355-7363.

Mahran AA, Osman HEH, El-Mawla AM, et al., 2011, Protective Effect of Zinc

(Zn) on the Histology and Histochemistry of Liver and Kidney af Albino Rat

Treated with Cadmium, Journal Cytology & Histology, Saudi Arabia, Vol

2:4, pp.1-9

Manggarwati AF, 2010, Uji Toksisitas Subkronis Ekstrak Valerian pada Tikus

Wistar. Studi Terhadap Gambaran Mikroskopis Ginjal dan Kadar

Kreatinin, Artikel Ilmiah, Fakultas Kedokteran Universitas Diponegoro,

Semarang.

Mastuti R, Cai Y, Corke H, 2010, Identifikasi Pigmen Betasianin pada Beberapa

Jenis Inflorescence Celosia, Jurnal Biologi UGM, Yogyakarta, pp. 664-672.

Mescher AL, 2011, Junqueira’s Basic Histology Text and Atlas, 13th ed, Indiana

University School of Medicine Bloomington, Bab 19.

Mitchell RN, Cotran RS, 2007, Jejas Adaptasi dan Kematian Sel, In: Kumar V,

Cotran RS, Robbins SL (eds), Buku Ajar Patologi Robbins, edisi VII, EGC,

Jakarta, vol. 1, pp. 26 -37.

xviii

Moreno DA, Garcia-Viguera C, Gil JI, et al., 2008, Betalains in the Era of Global

Agri-food Science, Technology and Nutritional Health. Phytochemistry

Reviews, Spain, vol. 7, pp.261-280.

Mun’im A, Azizahwati, Trastiana, 2008, Aktivitas Antioksidan dan Polyporaceae,

Jurnal Ilmiah Farmasi, vol. 5, no. 1.

Naderi N, Ghazali MH, Hussin MSA, et al., 2012, Charaterization and

Quantification of Dragon Fruit (Hylocereus polrhizus) Betacyanin

Pigments Extracted by Two Procedures, Pertanika J. Trop. Agric. Sci.,

Malaysia, vol. 35(1), pp. 33-40.

Nakhoul N, Batuman V, 2011, Role of Proximal Tubules in the Pathogenesis of

Kidney Disease, Nephrology Section, Tulane University Health Sciences

Center, Vol. 169, Diakses 24 Mei 2016.

<http://www.ncbi.nlm.nih.gov/pubmed/21252510>.

Nurliyana R, Zahir S, Suleiman M, et al., 2010, Antioxidant Study of Pulps and

Peels of Dragon Fruits: a Comparative Study, International Food Research

Journal, Malaysia, vol.17, pp. 367-375.

Panjuantiningrum F, 2009, Pengaruh Pemberian Buah Naga Merah (Hylocereus

polyrhizus) Terhadap Kadar Glukosa Darah Tikus Putih yang Diinduksi

Aloksan, Skripsi S1, Fakultas Kedokteran Universitas Sebelas Maret,

Surakarta.

Paulsen F, Waschke J, 2011, Sobotta Atlas Anatomi Manusia Jilid 2 Organ-Organ

Dalam, edisi 23, EGC, Jakarta, pp. 167.

Price SA, Wilson LM, 2006, Patofisiologi Konsep Klinis Proses - Proses Penyakit,

edisi ke-6, EGC, Jakarta.

Putri M, Busman H, Nurcahyani, 2013, Gambaran Histologis Tubulus Proksimal

Ginjal Mencit (Mus musculus L.) Jantan Yang Terpapar Kebisingan,

Seminar Nasional Sains & Teknologi V, Universitas Lampung, Lampung,

pp. 362-369.

Quaggin ES, Kreidberg AJ, 2008, Development of the Renal Glomerulus: Good

Neighbors and Good Fences, Development 135, Boston, USA, pp. 609-620.

Raharjo SS, Jusup AS, 2010, Efek Ekstrak Daun Krokot (Portulaca oleracea L.)

Sebagai Antioksidan Alami Terhadap Kadar Alanin Transaminase (ALT)

dan Gambaran Histologi Sel Hepar Rattus norvegicus L. yang Diberi

Minyak Goreng deep frying, Skripsi, Universitas Sebelas Maret, Surakarta.

Rebecca SPO, Boyce NA, Chandran S, 2010, Pigment Identification and

Antioxidant Properties of Red Dragon Fruit (Hylocereus polyrhizus),

African Journal of Biotechnology, Malaysia, Vol. 9(10), pp. 1450-1454.

xix

Redha A, 2010, Flavonoid: Struktur Sifat Antioksidatif dan Perannya dalam Sistem

Biologis, Jurnal Belian, Pontianak, vol. 9, pp. 196-202.

Sabir A, 2005, Aktivitas Antibakteri Flavonoid Propolis Trigona sp. Terhadap

Bakteri Streptococcus Mutan (in vitro), Majalah kedokteran Gigi (Dental

Journal), Makassar, vol. 38(3), pp. 135-41.

Sartika DAR 2009, Pengaruh Suhu dan Lama Proses Menggoreng (Deep Frying)

Terhadap Pembentukan Asam Lemak Trans, Makara Sains, Depok, vol. 13

(1), pp. 23-28.

Scandalions GJ, 2005, Oxidative stress: Molecular Perception and Transduction of

Signals Triggering Antioxidant Gene Defenses, Brazilian Journal of

Medical and Biological Research, USA, vol.38, pp. 995-1014

Scudamore CLC, 2014, A Practical Guide to the Histology of the Mouse, Mary

Lyon Centre, MRC Harwell, UK, pp.77, <

https://books.google.co.id/books?id=qBx0AgAAQBAJ&printsec=frontc

over&hl=id#v=onepage&q&f=false>

Sen S, Chakraborty R, 2014, Antioxidant Supplements: Friend or Foe?, Dalam:

Ravi V dan Yadav U (Eds), 2015, Free Radicals in Human Health and

Disease, Springer, India, pp. 293-296, <

https://books.google.co.id/books?id=aTppBQAAQBAJ&pg=PA294&dq

=antioxidant+and+free+radicals&hl=id&sa=X&redir_esc=y#v=onepage

&q=antioxidant%20and%20free%20radicals&f=false>.

Silalahi J, 2006, Antioksidan dalam Diet dan Karsiogenesis, Cermin Dunia

Kedokteran, Universitas Sumatera Utara, Medan, no 153.

Snell RS, 2012, Anatomi Klinis Berdasarkan Sistem, EGC, Jakarta.

Stevens FJ, Maier SC, 2008, Acrolein: Sources, Metabolism, and Biomolecular

Interactions Relevant to Human Health and Disease, Mol Nutr Food

Res, USA, vol.52(1), pp. 7-25

Stintzing FC, Scheibe A, Carle R, 2007, Betacyanin in Fruit from Red Purple

Pitaya (Hylocereus Polyrhizus) (Weber) Britton and Rose, Food Chemistry,

Germany, vol.77, pp. 101-106.

Sunarni T, 2005, Aktivitas Antioksidan Penangkap Radikal Bebas Beberapa

Kecambah Dari Biji Tanaman Familia Papilionaceae, Jurnal Farmasi

Indonesia, vol. 4, pp. 34-39.

xx

Tahir I, Wijaya K, Widianingsih D, 2003, Terapan Analisis Hansch Untuk Aktivitas

Antioksidan Senyawa Turunan Flavon/ Flavonol, Seminar on

Chemometrics- Chemistry Dept Gajah Mada University, Yogyakarta.

Tang CS, Norziah MH, 2007, Stablity of Betacyanin Pigments from Red Purple

Pitaya Fruit (Hylocereus polyrhizus): Influence of PH, Tempereture, Metal

Ions and Ascorbic Acid, Universiti Sains Malaysia, Penang, Malaysia, vol.

7(3), pp. 327-331.

Tapan E, 2005, Penyakit Degeneratif, Elek Media Komputindo, Jakarta.

Taliaz D, Assaf L, Roman G, et al., 2011, Resilience To Chronic Stress Is Mediated

By Hippocampal Brain-Derived Neurotrophic Factor, J Neurosci., Israel,

vol. 31(12), pp.4475–83.

Totani N, Ojiri Y, 2007, Mild Ingestion of Used Frying Oil Damages Hepatic and

Renal Cells in Wistar Rats, Journal of Oleo Science, Japan, Vol.56, pp. 261-

267.

Tremallen K, 2008, Oxidative Stress and Male Infertility – A Clinical Perspective,

Human Reproduction Update, South Australia, vol. 14 no.3, pp. 243-258.

Treuting MP dan Kowalewska J, 2011, Urinary System, In: Treuting MP dan

Dintzis MS (eds), Comparative Anatomy and Histology: A Mouse and

Human Atlas, 2011, First Edition, USA, pp.229-230, <

https://books.google.co.id/books?id=Bqn23_270Q8C&printsec=frontcover

&dq=comparative+anatomy+histology+a+mouse+and+human&hl=id&sa

=X&redir_esc=y#v=onepage&q=comparative%20anatomy%20histology

%20a%20mouse%20and%20human&f=false>.

Underwood JCE, 2004, General and Systemic Pathology, 4th ed, Edinburgh

London ,New York Oxoford–Philadephia St Louis Study, Toronto.

Unita L, Lubis RH, 2005, Profil Lipid Penderita Penyakit Ginjal Kronis pada

Predialisis dan Hemodialisis, Majalah Kedokteran Nusantara, Medan,

vol.38 no.2.

Widayati E, 2012, Oxidasi Biologi Radikal Bebas dan Antioxidant, Bagian Kimia-

Biokimia FK Unissula, Semarang

Wiardani KN, Moviana Y, Puryana SPGI, 2014, Jus Buah Naga Merah

Menurunkan Kadar Glukosa Darah Penderita DMT2, Jurnal Skala Husada,

Denpasar, vol. 11 no.1, pp. 59-66.

Wilson LM, 2006, Anatomi dan Fisiologi Ginjal dan Saluran Kemih, In : Price SA

dan Wilson LM (eds), Patofisiologi Konsep Klinis Proses-proses Penyakit,

Edisi 6 Vol. 2, EGC, Jakarta.

xxi

Winarsi H, 2007, Antioksidan Alami dan Radikal Bebas, Kanisus, Yogyakarta.

Wu CL, Hsu WH, Chen CY, et al., 2006, Antioxidant and Antiproliferative

activities of Red Pitaya, Food Chemistry, Vol. 95 Issue 2, pp. 319-327.

Xiao WH, Han LJ, Shi B, 2008, Microwave-assisted extraction of flavonoids from

Radix Astragali, Separat. Purif. Technol., vol 62, pp. 614– 618.

Yuliza FY, 2012, Identifikasi Betasianin dan Uji Antioksidan dari Ekstrak Daun

Bayam Merah (Amatanthus tricolor L) Serta Aplikasinya Sebagai Zat

Warna, Thesis, Program Pasca Sarjana Universitas Andalas, Padang.

Youngson R, 2005, Antioksidan Manfaat Vitamin C dan E Bagi Kesehatan,

Gramedia EGC.

Zainoldin KH, Baba AS, 2009, The Effect of Hylocereus Polyrhizus and Hylocereus

Undatus on Physicochemical, Proteolysis, and Antioxidant Activity in

Yogurt, World Academy of Science, Enginering and Technology 60, pp.

361-366.