DAFTAR ISI
HALAMAN SAMPUL DEPAN .................................................................... i HALAMAN JUDUL ...................................................................................... ii HALAMAN PENGESAHAN PEMBIMBING ............................................ iii HALAMAN PENGESAHAN PENGUJI ..................................................... iv HALAMAN PERNYATAAN ........................................................................ v KATA PENGANTAR.................................................................................. vi DAFTAR ISI ................................................................................................... viii DAFTAR GAMBAR ...................................................................................... xi DAFTAR TABEL .......................................................................................... xii DAFTAR LAMPIRAN .................................................................................. xiv INTISARI ....................................................................................................... xvii ABSTRACT .................................................................................................... xviii BAB I. PENDAHULUAN .............................................................................. 1 A. Latar Belakang Masalah ................................................................ 1 B. Perumusan Masalah ...................................................................... 3 C. Tujuan Penelitian .......................................................................... 4 D. Manfaat Penelitian ........................................................................ 4 BAB II. STUDI PUSTAKA ........................................................................... 5 A. Tinjauan Pustaka ........................................................................... 5 1.
Tanaman Purwoceng (Pimpinella alpina Molk) .................... 5 a. Morfologi Tanaman ........................................................... 5 b. Klasifikasi tanaman ........................................................... 6 c. Kandungan fitokimia ......................................................... 6 d. Status Penelitian Tanaman Purwoceng ............................. 15
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2.
Toksikologi ............................................................................ 15 a. Definisi Toksikologi .......................................................... 15 b. Prinsip Umum Toksikologi ............................................... 16 c. Faktor yang mempengaruhi Toksisitas.............................. 16 d. Mekanisme Efek Toksik .................................................... 17 e. Sifat Efek Toksik ............................................................... 19 f. Uji toksisitas ...................................................................... 19 g. Uji toksisitas Akut ............................................................. 19
3.
Pemilihan Hewan Uji ............................................................. 28 a. Tikus Putih ........................................................................ 28 b. Penganganan dan Pengendalian Hewan Uji ...................... 30 c. Kondisi Lingkungan .......................................................... 30 d. Parameter Fisik dan Fisiologis Tikus ................................ 30
4.
Keamanan Obat Tradisional ................................................... 30
B. Landasan Teori ............................................................................. 31 C. Kerangka Konsep ........................................................................ 32 D. Hipotesis ........................................................................................ 32 BAB III. METODE PENELITIAN ............................................................. 34 A. Alat dan Bahan ............................................................................... 34 1. Alat ............................................................................................. 34 2. Bahan .......................................................................................... 34 B. Cara Penelitian ................................................................................ 34 1.
Penyiapan Bahan Uji ................................................................ 34
2.
Pemilihan Hewan Uji ............................................................... 34
3.
Persiapan Hewan Uji ............................................................... 34
4.
Pengelompokan Hewan Uji ...................................................... 36
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5.
Preparasi Larutan Uji ................................................................ 36
6.
Tata Cara Pemejanan Dosis Sediaan ........................................ 36
7.
Pengamatan Gejala Toksik ....................................................... 38
8.
Penilaian LD50 .......................................................................... 39
9.
Pengukuran Berat Badan .......................................................... 39
C. Definisi Operasional Variabel ....................................................... 40 D. Analisis Hasil ................................................................................ 41 E. Alur Penelitian .............................................................................. 43 BAB IV. HASIL DAN PEMBAHASAN ..................................................... 44 A. Penetapan Dosis ............................................................................ 44 B. Ethical Clearance.......................................................................... 45 C. Potensi Ketoksikan Akut (LD50) ................................................... 45 D. Pengamatan Keadaan Fisik ........................................................... 48 E. Rerata Perubahan Berat Badan...................................................... 51 F. Keterbatasan Penelitian ................................................................. 59 BAB V. KESIMPULAN DAN SARAN ....................................................... 60 A. Kesimpulan ................................................................................... 60 B. Saran .............................................................................................. 60 DAFTAR PUSTAKA ..................................................................................... 61 LAMPIRAN .................................................................................................... 66
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DAFTAR GAMBAR
Gambar 1.
Akar tanaman purwoceng ........................................................ 7
Gambar 2.
Struktur dasar steroid ............................................................... 9
Gambar 3.
Struktur kimia stigmasterol ..................................................... 10
Gambar 4.
Struktur kimia sitosterol .......................................................... 11
Gambar 5.
Struktur kimia dasar glikosida triterpen .................................. 12
Gambar 6.
Struktur kimia dasar glikosida steroid ..................................... 12
Gambar 7.
Struktur kimia dasar glikosida alkaloid .................................... 12
Gambar 8.
Struktur kimia bergapten ......................................................... 13
Gambar 9.
Struktur kimia senyawa pinidine ............................................. 14
Gambar 10.
Struktur kimia senyawa mescaline .......................................... 14
Gambar 11.
Struktur kimia senyawa usambarensine .................................. 14
Gambar 12.
Diagram absorpsi dan distribusi zat-zat toksik (toksikan) ....... 18
Gambar 13.
Skema kerja dengan dosis awal 2000 mg/kg BB ................... 23
Gambar 14.
Skema uji statistik
Gambar 15.
Skema alur penelitian
................................................................. 42 ........................................................... 43
Gambar 16. Grafik perubahan berat badan rata-rata tikus betina terhadap waktu sampai 14 hari setelah pemberian sediaan uji secara oral dosis tunggal (2000 mg/kg BB) ................................................ 56 Gambar 17. Grafik perubahan berat badan rata-rata tikus jantan terhadap waktu sampai 14 hari setelah pemberian sediaan uji secara oral dosis tunggal (2000 mg/ kg BB) ............................................... 57
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DAFTAR TABEL
Tabel I.
Klasifikasi zat kimia nilai LD50 dari data toksisitas akut oral berdasarkan WHO ....................................................................... 24
Tabel II.
Kategori ketoksikan menurut Global Harmonized Classified System (GHS) ............................................................................... 25
Tabel III. Jumlah tikus yang mati pada pengamatan 24 jam pertama setelah pemejanan dosis tunggal sediaan uji larutan ekstrak akar purwoceng (Pimpinella alpina Molk) terstandar secara oral ....... 45 Tabel IV. Jumlah kematian tikus (% kematian) sampai 14 hari pemberian sediaan uji secara oral dosis tunggal ............................................. 45 Tabel V Hasil pemeriksaan kualitatif terhadap gejala-gejala toksik pada tikus putih betina galur Wistar selama 24 – 72 jam pertama setelah pemberian ekstrak akar purwoceng (Pimpinella alpina Molk.) terstandar secara oral dosis tunggal................................... 48 Tabel VI. Hasil pemeriksaan kualitatif terhadap gejala-gejala toksik pada tikus putih betina galur Wistar selama 14 hari setelah pemberian ekstrak akar purwoceng (Pimpinella alpina Molk.) terstandar secara oral dosis tunggal ............................................................... 49 Tabel VII. Hasil pemeriksaan kualitatif terhadap gejala-gejala toksik pada tikus putih jantan galur Wistar selama 24 – 72 jam pertama setelah pemberian ekstrak akar purwoceng (Pimpinella alpina Molk.) terstandar secara oral dosis tunggal................................... 49 Tabel VIII. Hasil pemeriksaan kualitatif terhadap gejala-gejala toksik pada tikus putih jantan galur Wistar selama 14 hari setelah pemberian ekstrak akar purwoceng (Pimpinella alpina Molk.) terstandar secara oral dosis tunggal ............................................................... 50 Tabel IX. Hasil analisis uji normalitas (Uji Shapiro-Wilk) dan uji varian (Test Homogenety of variance) rerata perubahan berat badan hewan uji perhari) hewan uji tikus betina selama 14 hari ............. 53
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Tabel X. Hasil analisis uji normalitas (Uji Shapiro-Wilk) dan uji varian (Test Homogenety of variance) rerata perubahan berat badan hewan uji perhari hewan uji tikus jantan selama 14 hari .......................... 53 Tabel XI. Perubahan berat badan rata-rata tikus betina, 14 hari setelah pemberian sediaan uji secara oral dosis tunggal ........................... 54 Tabel XII. Perubahan berat badan rata-rata tikus jantan, 14 hari setelah pemberian sediaan uji secara oral dosis tunggal ........................... 56
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DAFTAR LAMPIRAN
Lampiran 1. Surat keterangan sehat hewan uji ............................................... 66 Lampiran 2. Sertifikat analisis ekstrak terstandar akar purwoceng (Pimpinella alpina Molk.) ......................................................... 67 Lampiran 3. Sertifikat ethical clearance.......................................................... 71 Lampiran 4.
Pemeriksaan Fisik Tikus I betina kelompok perlakuan kombinasi kriteria Balasz dan Guidance Document on the Recognition, Assessment, and use of Clinical Signs as Humane Endpoints for Experimental Animals used in Safety Evaluation selama 14 hari........ ................................................ 72
Lampiran 5. Pemeriksaan Fisik Tikus I betina kelompok kontrol kombinasi kriteria Balasz dan Guidance Document on the Recognition, Assessment, and use of Clinical Signs as Humane Endpoints for Experimental Animals used in Safety Evaluation selama 14 hari........... ............................................ 89 Lampiran 6. Pemeriksaan Fisik Tikus I jantan kelompok perlakuan kombinasi kriteria Balasz dan Guidance Document on the Recognition, Assessment, and use of Clinical Signs as Humane Endpoints for Experimental Animals used in Safety Evaluation selama 14 hari....... ................................................. 106 Lampiran 7. Pemeriksaan Fisik Tikus I jantan kelompok kontrol kombinasi kriteria Balasz dan Guidance Document on the Recognition, Assessment, and use of Clinical Signs as Humane Endpoints for Experimental Animals used in Safety Evaluation selama 14 hari........ ................................................ 123 Lampiran 8. Data berat badan tikus betina, 14 hari setelah pemberian sediaan uji secara oral dosis tunggal ........................................ 140 Lampiran 9. Data berat badan tikus jantan, 14 hari setelah pemberian sediaan uji secara oral dosis tunggal ........................................ 141 Lampiran 10. Pengamatan fisik gejala-gejala klinis dalam uji toksisitas menurut kriteria Balazs............................................................. 142 Lampiran 11. Pengamatan fisik gejala-gejala klinis dalam uji toksisitas menurut kriteria Guidance Document on the Recognition,
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Assessment, and use of Clinical Signs as Humane Endpoints for Experimental Animals used in Safety Evaluation ............... 143 Lampiran 12. Data berat badan hewan uji hasil uji analisis statistik tikus betina kelompok perlakuan selama 14 hari .............................. 144 Lampiran 13. Data berat badan hewan uji hasil uji analisis statistik tikus jantan kelompok perlakuan selama 14 hari .............................. 145 Lampiran 14. Perhitungan larutan stok .......................................................... 146
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