Hasil Pencarian  ::  Simpan CSV :: Kembali

"Latar Belakang: Penurunan sensitivitas hingga resistensi terhadap tamoksifen sering terjadi dalam pengobatan kanker payudara jangka panjang. Salah satu penyebab utamanya adalah peningkatan ekspresi transporter efluks P-glikoprotein (P-gp) dan Breast Cancer Resistance Protein (BCRP). Kurkumin diketahui sebagai penghambat P-gp dan BCRP. Pemberian kurkumin pada sel yang telah menurun sensitivitasnya terhadap tamoksifen diharapkan mampu meningkatkan sensitivitas sel kanker payudara terhadap tamoksifen melalui penghambatan kedua transporter tersebut. Metode: Sel MCF-7 dipaparkan tamoksifen 1 µM selama 10 pasasi (sel MCF-7(T)), kemudian dianalisis perubahan sensitivitas sel terhadap tamoksifen melalui viabilitas sel dan ekspresi mRNA P-gp dan BCRP. Pada sel MCF-7(T), kurkumin diberikan dalam dosis 5, 10, dan 20 µM dengan atau tanpa tamoksifen selama 5 hari dan dianalisis viabilitas sel dan ekspresi mRNA P-gp dan BCRP pada hari ke-2 dan 5. Sebagai kontrol positif, verapamil 50 µM digunakan sebagai penghambat P-gp, ritonavir 15 µM dan nelfinavir 15 µM sebagai penghambat BCRP. Hasil: Setelah diberikan tamoksifen 1 µM selama 10 pasasi (44 hari), sel MCF-7(T) menurun sensitivitasnya terhadap tamoksifen yang dibuktikan dengan terjadinya pergeseran CC50 sebesar 32,08 kali, peningkatan viabilitas sel sebesar 106,4%, dan peningkatan ekspresi mRNA P-gp dan BCRP sebesar 10,82 kali dan 4,04 kali. Pemberian kurkumin dengan atau tanpa tamoksifen selama 5 hari dapat menurunkan viabilitas sel dan ekspresi mRNA P-gp dan BCRP (p < 0,05). Kesimpulan: Kurkumin meningkatkan sensitivitas sel MCF-7(T) terhadap tamoksifen yang ditandai dengan penurunan viabilitas sel dan ekspresi mRNA P-gp dan BCRP. Peningkatan sensitivitas tersebut diduga terjadi melalui penghambatan ekspresi mRNA P-gp dan BCRP oleh kurkumin.

---

Background: Decrease of sensitivity or resistance to tamoxifen occurs after long-term treatment in breast cancer. One of the major factor in tamoxifen resistance is overexpression of efflux transporter P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). Curcumin has been known as inhibitor of P-gp and BCRP. The addition of curcumin to tamoxifen resistant cells is expected to increase the sensitivity of breast cancer cells to tamoxifen.

Methods: MCF-7 breast cancer cell line was exposed with tamoxifen 1 µM for 10 passage (MCF-7(T)), then cell viability and mRNA expression of P-gp and BCRP were analyzed. To the MCF-7(T) cells, curcumin of 5, 10, dan 20 µM with or without tamoxifen was given for 5 days and cell viability and mRNA expression of P-gp and BCRP were analyzed on day 2 and 5. As positive control, verapamil 50 µM was used as P-gp inhibitor, ritonavir 15 µM and nelfinavir 15 µM were used as BCRP inhibitor.

Results: The administration of tamoxifen 1 µM for 10 passage (44 days), caused a decreased of MCF-7(T) cells sensitivity to the drug, with 32,08 times reduction in CC50 towards tamoxifen, increased of cell viability of 106,4%, and increased mRNA expression of P-gp and BCRP mRNA of 10,82 and 4,04 fold, respectively. The administration of curcumin with or without tamoxifen for 5 days reduced cell viability and the mRNA expression of P-gp mRNA and BCRP (p < 0,05).

Conclusion: Curcumin increased MCF-7(T) sensitivity to tamoxifen, characterized by decreased of cell viability and mRNA expression of P-gp and BCRP. Increased of sensitivity was estimated at least in part through inhibition of P-gp and BCRP mRNA expression by curcumin. "

"ABSTRAKDasar (Riset Kesehatan Dasar / Riskesdas) yang dilakukan oleh Departemen Kesehatan Indonesia tahun 2010 melaporkan bahwa 17,9 persen (17,9%) dari anak-anak di Indonesia dengan usia di bawah 5 tahun memiliki masalah gizi buruk dan 14 persen ( 14%) di antara mereka memiliki masalah obesitas. Makanan sehari-hari diduga menjadi penyebab masalah gizi ini terutama penggunaan Monosodium L-glutamat (MSG) yang banyak digunakan sebagai aditif makanan dan zat untuk merangsang nafsu makan. Muncul beberapa pertanyaan tentang hubungan antara konsumsi MSG dan kenaikan berat badan dan hubungan antara efek neurotoksisitas MSG dengan kerusakan sel-sel saraf di otak. Dan apakah kerusakan sel-sel saraf di otak ini mengalami regenerasi atau menjadi persisten?Penelitian ini dilakukan untuk menentukan dampak dari MSG dalam berat badan dan perkembangan otak pada anak tikus dengan usia 7 dan 14 hari di mana ibu mereka diberi MSG selama hamil. Semua anak tikus juga diamati untuk perilaku mereka.Metode: Rancangan eksperimental in vivo dengan random sampling. Subyek adalah 25 tikus betina (Rattus novergicus) galur Sprague Dawley yang dibagi menjadi 5 kelompok (kelompok kontrol, grup pelarut dan 3 kelompok perlakuan MSG selama kehamilan dengan dosis 1200mg, 2400mg dan 4800mg/kg/day). Ketika tikus hamil melahirkan anaknya diamati sampai usia 7 dan 14 hari. Dua ekor anak tikus diambil secara acak dari tiap induk tikus lalu ditimbang berat badannya. Otak dari anak tikus diisolasi, ditimbang dan diwarnai dengan hematoxylin-eosin (HE) pewarnaan. Photomicrographs dari slide histologis diamati oleh optilab dan dianalisis dengan program Optic Raster. Parameter yang dianalisis dalam penelitian ini adalah penurunan berat badan, kerusakan sel-sel saraf dalam nukleus arkuata dan daerah paraventrikular dari hipotalamus dan perilaku anak tikus pada usia 7 dan 14 hari.Hasil: MSG dapat menembus blood plansental barrier dan blood brain barrier anak tikus pada usia 7 dan 14 hari ketika ibu mereka diberikan MSG selama hamil. Berat badan anak tikus usia 7 hari lebih rendah pada kelompok MSG dengan dosis 4800mg jika dibandingkan dengan kelompok kontrol dan kelompok pelarut 1200 mg dan 2400 mg. Namun peningkatan berat badan dengan pemberian MSG 4800 mg lebih tinggi jika dibandingkan dengan kelompok MSG dosis 1200mg dan 2400mg. Pada anak tikus usia 14 hari, ditemukan kenaikan berat badan lebih tinggi secara signifikan pada kelompok MSG dengan dosis 4800mg dibandingkan dengan 1200mg dan 2400mg. Berat otak sedikit lebih rendah pada usia 7 dan 14 hari pada kelompok MSG 4800mg . Kerusakan sel saraf dalam nukleus arkuata dan di daerah paraventrikular dari hipotalamus secara signifikan lebih tinggi pada kelompok MSG 4800mg . Perubahan perilaku yang diamati pada anak tikus dengan kelompok MSG 4800mg pada usia 7 dan 14 hari terlihat jelas dibandingkan kelompok kontrol dan MSG 1200 mg dan 2400 mg.Kesimpulan: Asupan MSG selama kehamilan menyebabkan perubahan berat badan, berat otak dan kerusakan sel-sel saraf di daerah arkuata dan hipotalamus paraventrikular pada anak tikus dengan usia 7 dan 14.

---

ABSTRACT

Background: Good Nutrition intake is the most important factor that determines the health status of our next generation. However the Basic Health Research (Riset Kesehatan Dasar / Riskesdas) conducted by the Indonesian Ministry of Health in 2010 reported that 17.9 percent (17.9%) of the children in Indonesia with the age under 5 years old had the problem of malnutrition and 14 percent (14%) among them had the problem of obesity. Daily food was suggested to become a cause of malnutrition problem especially the use of Monosodium L-glutamate (MSG) which is widely used as food additive and a substance to stimulate the appetite. There are some questions about the correlation of MSG consumption and weight gain and the correlation of neurotoxicity effect of MSG with the damage of neuronal cells in the brain. Another question is whether the damage of neuronal cells in the brain is persistent or not. This study was conducted to determine the effects of MSG in the weight gain and in the development of the brain in the rat pups with age of 7 and 14 days in which their mother were given the MSG during pregnancy. The rat pups were also observed for their behavior.

Methods: The experimental design was in vivo studies with randomized sampling. Subjects were 25 female rats (Rattus novergicus)of Sprague-Dawley strain which are divided into 5 groups (control group, solvent group and 3 MSG treatment groups during gestation given MSG in the dose of 1200mg/kgbw/day, 2400mg/kgbw/day and 4800mg/kgbw/day). Upon giving birth the pups were observed until the ages of 7 and 14 days. Two pups from each mother rat were taken randomly. The brain of the rat pups were isolated and stained with hematoxylin-eosin (HE) staining. Photomicrographs of the histological slides were taken by optilab and were analyzed with Image Raster program. The parameters that were analyzed in this experiment were weight body loss, the damage of neuronal cells in the arcuate nucleus and paraventricular area of hypothalamus and the behavior of the pups at age of 7 and 14 days.

Results: High dose MSG penetrate the placental blood barrier and the blood brain barrier in the brain of rat pups with the age of 7 14 days when their mothers were administered with MSG during their pregnant. The body weights of pups with age of 7 days were lower in the MSG treated group with the dose of 4800mg than that in the control and solvent groups. However body weigh were higher in the MSG treated groups of 1200mg/kgbw/day and 2400mg/kgbw/day than those in the control and solvent groups. In the 14 days pups, the body weight were higher significantly in the MSG treated groups with the dose of 4800mg/kgbw/day compared to the 1200mg/kgbw/day and 2400mg/kgbw/day. The weight of the brain was slightly lower at the age of 7 and 14 days in the 4800mg MSG treated group. The neuronal cell damage in the arcuate nucleus and in the paraventricular area of hypothalamus was significantly higher in the 4800mg MSG treated group. The behavior changes were observed in the pups with the 4800mg MSG treated group at the age of 7 and 14 days.

Conclusion: Intake of MSG during gestation causes changes in body weight, brain weight and damage of neuronal cells in the arcuate and paraventricular area of hypothalamus in rat pups of the age of 7 and 14."

"Pada keadaan hipoksia sel aksn berganti metabolisme dari tipe aerob Ire tipe yang lebih anaerob, yang lebih sedikit menghasilkan energi. Untuk memenuhi kebutuhan energi yang sama, set pada keadaan hipoksia meningkatkan konsurnsi glukosa. Penelitian ini bertuju.an untuk mengetahui gambaran adaptasi metabolisme otot pada tikus yang dibuat hipoksia dibandingkan dengan penyu hijau (Chelonia mydas). Penyu bijau merupakan hewan yang bernafas dtngan paru-paru namun dapat berakti.vitas lama di bawah air laut.Sejumiah tikus ditempatkan pada kandang hipoksia (tekanan l atm,dan kandungan o, 10%) selama I, 7 14, dan 21 hari. Pada akhir periode hipoksia setelah euthanasia. otot dianalisis untuk pengukuran konsumsi glaktivitas spesifik LDH dan etektroforesis isozim LDH. Analisis yang sarna juga di1akukan pada penyu yang ditempatkan pada kondisi nonnoksia.Konsumsi glukosa dan aktivitas LDH meningkat sejalan dengan lamanya hipoksia pada otot tikus, sedangkan isozim LDH tidak mengalami pcrubahan po1a.; kecuali peningka:tan LDH 4 dan LDH 5. Konsumsi glukosa dan aktivitas spesifik LDH otot penyu Iebih. tinggi dibanding otot tikus dan hanya terdapat satu tipe isozim LDH yaitu LDH 4 yang merupakan isozim LDH anaerob. Hasil penelitian menunjukkan adaptasi sel otot terhadap hipoksia, dengan mengubah metabolisme aerob menjadi lebih anaerob.

---

During hyPOxia, there is a shift ftom aerobic to anaerobic metabolism which results in the production of less ATP. 1n order to meet the same energy needed, the hypoxic cells have to increase the glucose consumption rate. In this study, we described the muscle metabolic adaptation in globally hypoxic rats as wcU a<;. in sea turtles (Chelonia mydm), the latter animals are well known as lung breathing species which spend most of their time under sea water.Rats were placed in a hypoxic chamber (I atrn, 0, l 0 Va! %) for I, 7, 14 and 21 days. At the end of each period, after euthanasia their muscles were analyzed for glucose metabolism rate, total specific LDH activities and LDH isozymes electrQphoresis. The same a!lalysis was made in sea turtle muscles which were placed in normal condition.Glucose consumption rates and LDH activities increased proportionally with the duration of hypoxic state in rats, whereas for LDH isozymes. there were no any change in pattern except for LDH 4 and LDH 5, which was more prominent the course of hypoxia. On the other hand, even in normoxic condition, sea turtles muscles consumed higher amount·of glucose. showed much higher of total specific LDH activities and had only one type of LDH isoZ)'Ule, i.e. LDH 4, which is anaerobic isozyme of LDH.The results suggest that during adaptation to hypoxia, the metabolism of aerobic muscle of rat switch to more anaerobic pattern and that sea turtle was genetlcally set fur hypo-xia condition."

"Latar Belakang : Acalypha indica Linn. merupaksn tanaman yang mudah didapat tumbuh .Sepanjang tahun dan bisa ditemukan di kebun, halaman rumah maupun tempat-tempat pembuangan sampah. Semua bagian dari tanaman ini bisa digunakan dalam pengobatan trndisiooal untllk menangani berbagai masalah kesehatan. Pada penelitian sebelumnya didapatkan data bahwa ekstrak Acalypha indica Linn. terhukti memiliki efek. Sebagai neuroproteksi dan neuroterapi pada neuromuscular junction jaringan kstak dan mampu menghambat efek neurotoksik pada jaringan kalak. Oleh karena itu, ekstrak air akar Acalypha indica Linn. bisa mempengaruhi perbaikan neuron hipokampus pascahipoksia serebri. Tujuan : untllk menganalisa kerusakan sel neuron hipokampus pascahipoksia setelah pemberian ekstrak air akar Acalypha indica Linn. Metode penelitian : 30 ekor tikss Sprague Dawley tetbagi secara acak dalarn enam kelompok. Kelompok hlpoksia, tikss dimasukkan ke dalam sungkup hipoksia yang mengandung gas campuran (02 10% dan nitrogen 90 %) selama tujuh hari, untuk kelompok reoksigenasi tikss dibiarken mengbirup udara bebas. Setelah perlakuan hipoksia. Tiga kelompok terapi lainnya, setelab perlakuan hipoksia tikss kemndian dilanjutkan dengan pemberian ekstrak air akar Acalypha indica Linn pada dosis 300, 400 dan 500 mglkg BB selama tujuh hari. Kriteria penilaian yang digunakan dalam studi ini adalah jumlah sel rusak neuron hipokampus den gao mengamati : bentuk sel, ada tidaknya kodensasi kromatin, piksotik dan rasio sitoplasma dengan inti setelah pewaraan hemaktosilin eosin. Hasil : ekstrak air akar Acalypha indica Linn. pada dosis 400 dan 500 mg/kg BB secara signitikan mampu memperbaiki kerusakan sel neuron ( efek neuroterapi) hipokampus pascabipoksia serebral (p = 0,0 I). Kesimpulan : ekstrak air akar Acalypha indica Linn memiliki efek neuroterapi pada dosis 400 dan 500 mglkg BB.

---

Background : Acalypha indica Linn is a common herb which can easily be found elsewhere in Indonesia, All the parts of plants are used in various traditional therapy for some diseases. Previous studies showed that Acalypha indica Linn extracts have neuro-protective and neuro-therapy effects on neuromuscular junction and inhibit neurotoxin on isolated frog tissues. Thus, administration of aqueous extracts of Acalyjpha. indica Linn root was assumed to improve hippocampus neuron injury after cerebral hypoxia.

Objective : To investigate the effects of aqueous extracts of Acalypha indica Linn root on hippocampus neuron injury after cerebral hypoxia in the rat.

Methods : Thirty male Sprague Dawley with 200-250 gr Body weight of rats were divided into six groups randomly. The rats were housed in hypoxic chamber containing gas mixture of I0 % O2 and 90 % N2 for seven days, followed by administration of 300, 400 and 500 mg/kg BW aqueous extracts of A. indica Linn root for seven days.. The other group was exposed to room air after hypoxia. The parameters measured were hippocampal cell damage ie : the quantity and type of hippocampal cell, chromatin condensation, pycnotic and cytoplasm nucleus ratio using hematoxyline eosin staining.

Result : The aqueous extracts of A. indica Linn root of 400 and 500 mg/kg BW improve hippocampus neuron injury (neurothcrapy effect) alter cerebral hypoxia significantly (p = 0,0l).

Conclusion : The aqueous extracts of A. indica Linn roots have neurotherapy effects on hippocampal neuron after cerebral hypoxia of 400 and 500 mg/kg BB."

"Penelitian ini bertujuan menganalisis aktivitas spesifik enzim MnSOD, katalase dan OPT pada sel hati tikus yang diinduksi hipoksia sistemik dan hubungannya dangan stres oksidatif. Sampel penelitian ini adalah jaringan had tikus jantan strain Sprague Dawley (Rattus novergieus L), yang diinduksi hipoksia sistemik kmnik 1,7,14 dan 21 hari. Pada homogenat hati tikus dilakuksn beberapa pomeriksaan, yaitu pemeriksaan aktivitas spesifik MnSOD, aktivitas spesifik katalase, aktivitas spesifik enzim OPT, kadar MDA dan pemeriksaan senyawa karbonil.Dari penelitian ini didapatkan hasil tidak adanya perubahan bennakna pada aktivitas spesifik MnSOD, OPT, dan kadar karbonil. Pada hipoksia 7 dan 21 hari terjadi penurunan bermakna aktivitas spesifik katalase, dan kadar MDA menurun bertuakna peda bipoksia 21 hati.Dari hasil analisis didapat bubungan negatif antara MnSOD dan katalase dengan kerusakan oksidatif, disimpulkan bahwa MnSOD dan kstalase berperan dalam mencegah kerusakan oksidatif. Analisis hubungan aktivitas spesifik OPT dengan kerusakan oksidatif didapat hubungan negatif. Hal ini mengindikasikan bahwa penurunan OPT di hati dapat dipaksi sebagai indikator kerusakan oksidatif.Dari basil penelitian ini disimpulkan bahwa jaringan hari memiliki sistem pertahanan antioksidan yang adekuat, sehingga sel hati cukup tahan terhadap terjadinya kerusaknn oksidalif.

---

The aim of this study was to analyze the specific activities of MoSOD, catalase and GPT in rat liver cells induced by systemic hypoxia related to oxidative stress. The samples were obtained from liver tissue of Spmgue Dawley rats at days I, 7, 14, and 21 of citronic systemic hypoxia and were used to measure specific activity ofMnSOD, catalase, GPT, and the levels ofMDA, and protein carbonyis.

Results showed that there were not significant alteration of specific activity ofMnSOD, ofGPT, and levels of carbonyls. At days 7 and 21 of hypoxic induction there were significant decrease of catalase specific activity. Levels of MDA significant decreased at days 21.

Based on correlation analyzing it can be concluded that MnSOD and catalase had a role in prevent oxidative damage. Correlation analyzing of OPT specific activity and oxidative damage showed negative correlation. This means that decreased of GPT specfic activity in liver could be used as oxidative damage indicator.

It is concluded that liver tissue provided with adequate antioxidant defense mechanism which makes Uver cells survive during hypoxic oxidative insult."

"Latar Belakang : Kafein merupakan substansi yang paling banyak di gunakan di seluruh dunia, hampir 80 % dari populasi merupakan pengguna rutin. Efek dari penggunaan kafein bergantung kepada beberapa faktor, antara lain jenis, intensitas dan durasi dari kerja flsik, dosis kafein. Pada suatu populasi, 75% orang dewasa dalam melakukan aktivitas sehari-hari menggunakan energi yang sama pada saat melakukan kerja fisik ringan. Tubuh manusia memiliki kemampuan untuk menyimpan kelebihan energi. Cadangan energi tersebut akan dipergunakan melalui proses penguraian kembali kreatin fosfat rnenjadi ATP Serta Iipolisis, glikogenolisis dan glukoneogenesis. Kafein adalah inhibitor kompetitif dari reseptor dengan ligan adenosine di adiposit. Kafein menghilangkan efek penekanan adenosin terhadap lipolisis. Kafein bersama homlon-honnon lipolitik (epinefrin, norepinefiin, glukagon dan hormon pertumbuhan) bersinergi dalam meningkatkan kadar asam lemak bebas. Kafein dapat meningkatkan ketersediaan oksigen melalui mekanisme blok reseptor adenosin, sehingga efek penekanan adenosin terhadap neuron-neuron di PreB6t.zinger kompleks dalam pembentukkan irarna pernafasan hilang, dan menyebabkan peningkatan frekuensi pemafasan. Kondisi tersebut, membuat kafein dikenal sebagai substansi yang dapat meningkatkan kemampuan Esik dan menurunkan tingkat kelelahanTujuan : Mengetahui pengaruh kafein terhadap kadar asam lemak bebas, frekuensi pemafasan dan tingkat kelelahan.Metode : Penelitian menggunakan disain cross over, pada 8 laki-laki dewasa yang terbagi menjadi dua kelompok yaitu kelompok yang mendapat kafein 3 mg/kg.bb dan kelornpok kontrol yang mendapatkan plasebo. Kadar asam lemak dan frekuensi pemafasan diukur pada saat sebelum perlakuan, sesudah perlakuan dan sesudah kerja fisik. Tingkat kelelahan diukur selama kerja fisik.Hasil : Setelah kerja fisik kadar asam lemak bebas kelompok kafein mengalami peningkatan yang bermakna dibandingkan kelompok plasebo, frekuensi pernafasan pada kelornpok kafein meningkat tetapi tidak berbeda bemmakna dibanding kelompok plasebo, tingkat kelelahan pada kelompok kafein lebih rendah dibanding kelompok plasebo dan berbeda bermakna secara statistik.Kesimpulan : Penggunaan kafein 3 mg/kg.bb secara bermalma dapat meningkatkan kadar asam lemak bebas sesudah kerja fisik dan menurunkan tingkat kelelahan selama kerja fisik. Tetapi tidak meningkatkan frekuensi pernafasan secara bermakna.

---

Background : Caffeine is the most widely used substance in the world, its regular users comprise almost 80% of the population. The effects of using caffeine depend on a number of factors such as the type, intensity, and duration of physical work, and the dose of caffeine. In a particular population, 75% of adults in doing their daily routine spend as much as energy as when they do light exercise. Human body processes the ability to store extra energy. The stored energy will o utilized through decomposition of creatine phosphate into ATP and lipolysis, glycogenolysis ang gluconeogenesis. Caffeine is a competitive inhibitor of a receptor with ligand adenosine in adipocyte. Caffeine bounds to the receptor, but since it inhibits the adenosine effect, caffeine increases lipolysis. Caffeine along with lipolytic hormones (epinephrine, norepinephrine, glucagons and growth hormone) increases the levels of free fatty acids. Caffeine can increase the availability of oxygen through adenosine receptor blockade mechanism, which results in the disappearance of the pressing effect of adenosine against neurons of PreB6tzinger complex in the formation of breathing pattern, and it can increase breathing frequency. That condition makes caffeine known as a substance which can increase physical ability and reduce the level of fatigue.Objective : To discover the effects of caffeine on the levels of free fatty acids, breathing frequency, and the level of fatigue.Method : The research used the cross»over design in 8 males, conducted in two groups: the group receiving 3 mg/kg body weight and the control group receiving placebo. The levels of fatty acids and breathing frequency were measured prior to the procedure, after the procedure and after exercise. The level of fatigue was measured during exercise.Results : After exercise, levels of free fatty acids in the group with the caffeine increased significantly than that in the group receiving placebo, the breathing frequency in the caffeine group increased but it was not significantly than that in the palcebo group, and the level of fatigue in the caffeine group was lower significantly than that in the placebo group.Conclusion : The use of caffeine 3 mg/'kg body weight significantly increases the levels of free fatty acids after exercise and reduces level of fatigue during exercise. However, it does not cause a significant increase in the breathing frequency."

"Hati merupakan organ yang berperan penting dalam metabolisme zat terutama obat-obatan sehingga organ ini rentan terhadap kerusakan. Salah satu obat yang dapat menyebabkan kerusakan hati adalah doksorubisin. Hal ini disebabkan karena struktur kimia dan proses metabolisme doksorubisin dapat membentuk sejumlah metabolit yang bersifat radikal bebas. Radikal bebas yang diproduksi doksorubisin menyebabkan berkurangnya antioksidan endogen, mengganggu keseimbangan besi intraselular sehingga mencetuskan kerusakan oksidatif. Berdasarkan hal tersebut, kerusakan oksidatif yang dipicu oleh doksorubisin dapat dicegah dengan pemberian antioksidan eksogen. Salah satu bahan bioaktif yang terbukti memiliki efek antioksidan adalah mangiferin. Efek antioksidannya berhubungan dengan sifat scavenging radikal bebas dan sifat kelator besinya. Pemberian senyawa ini diasumsikan dapat melindungi atau mencegah kerusakan oksidatif sel. Penelitian ini bertujuan untuk membuktikan efek protektif mangiferin terhadap kerusakan hati pada tikus yang diberikan doksorubisin. Pada penelitian ini, tikus dibagi menjadi lima kelompok, masing-masing kelompok terdiri dari lima ekor tikus. Tikus pada kelompok perlakuan diberikan injeksi doksorubisin intraperitoneal (dosis kumulatif 15 mg/kgBB) dan kelompok kontrol diberikan minyak jagung oral. Mangiferin (dosis 50 mg/kgBB dan 100 mg/kgBB) dan silymarin diberikan secara oral selama lima minggu. Setelah lima minggu, tikus dimatikan, darah dan jaringan hati dikumpulkan untuk analisis histopatologi dan penentuan SGOT, SGPT, MDA, SOD dan GSH. Hasil penelitian menunjukkan bahwa pemberian doksorubisin dengan dosis kumulatif 15 mg/kgBB selama dua minggu dapat menyebabkan kerusakan sel hati, meningkatkan kadar MDA, dan menurunkan pertahanan antioksidan endogen di hati. Pemberian mangiferin 50 dan 100 mg/kgBB selama lima minggu dapat mengurangi kerusakan sel hati yang ditandai dengan penurunan aktivitas SGPT dan SGOT, penurunan kadar MDA, dan peningkatan aktivitas SOD dan kadar GSH sel hati (p < 0.05). Perbaikan pada parameter-parameter ini mengindikasikan bahwa mangiferin memiliki efek proteksi terhadap kerusakan hati pada tikus yang diberikan doksorubisin.

---

Liver is an organ that plays an important role in the metabolism of xenobiotics. However, since it is actively involved in drug metabolism, it is also subject to damage caused by toxic drugs or metabolites. One of the drugs that caused liver damage is doxorubicin. The liver damaging effect of doxorubicin is determined to its chemical structure and toxic metabolites which can produce free radical molecules. The free radicals produced by doxorubicin cause depletion of antioxidant in the body, disrupt the balance of intracellular iron and lead to oxidative stress. Based on this consideration, the oxidative stress induced by doxorubicin should be diminished by means of exogenous antioxidant administration. One of the bioactive ingredient that has been shown to have antioxidant effects is mangiferin; its antioxidant properties relate to free radical scavenging and iron chelating effect. This compound is expected to protect against or prevent oxidative damage caused by doxorubicin to cells.

This study aims to investigate the protective effect of mangiferin against liver damage-induced doxorubicin. There were five groups of rats, consisting five each group. The animals in the study groups were treated with intraperitoneal doxorubicin (cumulative dose 15 mg/kgBW for two weeks) and control group was given oral corn oil. Mangiferin (dose 50 mg/kgBW and 100 mg/kgBW) and silymarin were given daily by oral administration for five weeks. After sacrifice, blood and liver tissue samples were collected for histopathological analysis and determination of SGOT, SGPT, MDA, SOD, and GSH.

The results showed that administration of cumulative doses of doxorubicin to 15 mg/kgBW for two weeks caused liver cell damage, increased MDA level and decreased activities of SOD and GSH level in liver. The supplementation of mangiferin 50 and 100 mg/kgBW for five weeks reduced liver cell damage as shown by decreased activities of SGPT and SGOT, decreased MDA level, and increased activities of liver SOD and GSH levels. (p <0.05). These results showed that mangiferin has a protective effect against liver damage induced by doxorubicin in the rat."

"ABSTRACTKondisi hipoksia menyebabkan stabilisasi HIF-1α, yang mengatur ekspresi beberapa gen seperti Carbonic Anhydrase 9 (CA9). CA9 merupakan enzim yang memediasi homeostasis pH melalui reaksi reversibel CO2 dan H2O menjadi HCO3 - and H+.Aktivitas enzim CA pada sel tubulus ginjal yang meningkat seiring dengan kondisi hipoksia menyebabkan peningkatan ion H+ dalam urin. Pada kondisi tersebut, sel tubulus ginjal akan mensekresikan NH3 (amonia) ke dalam cairan tubulus sebagai penyangga sehingga sekresi H+ dari sel tubulus dapat terus berlangsung. NH3 akan bereaksi dengan H+ membentuk NH4 + (amonium). NH3 dihasilkan dari deaminasi glutamin oleh enzim glutaminase yang disintesis di dalam sel tubulus. 25 tikus jantan Sprague Dawley (Rattus norvegicus L.) dibagi menjadi 5 kelompok. Sebanyak 20 tikus diinduksi dengan hipoksia (O2 10%) sebagai pemicu stabilisasi HIF-1α dan diobservasi selama 1, 3, 5, dan 7 hari pasca induksi. Kelompok kontrol tidak mendapat perlakuan induksi hipoksia. Semua tikus kemudian didekapitasi. Dari sampel ginjal, dilakukan pemeriksaan ekspresi mRNA HIF-1α, CA9, dan Gls1 (dengan real time RT-PCR), protein HIF-1α (dengan ELISA) serta aktivitas enzim CA total dan glutaminase. Ekspresi tertinggi mRNA HIF-1α, dan Gls1 dicapai pada hari ke-5 sedangkan ekspresi tertinggi mRNA CA9, dicapai pada 7 hari pasca induksi hipoksia. Konsentrasi protein HIF-1α sendiri tidak berbeda bermakna untuk semua kelompok. Aktivitas tertinggi enzim CA dan glutaminase dicapai pada kelompok 5 hari. Peningkatan mRNA dan aktivitas CA9 dan Gls1 pada kondisi hipoksia menunjukkan peran penting keduanya dalam menjaga homeostasis pH pada ginjal. Peningkatan mRNA CA9 dan Gls1 juga seiring dengan peningkatan mRNA HIF-1α yang menunjukkan bahwa ada korelasi positif antara HIF-1α dengan kedua gen tersebut.

---

ABSTRACT

Hypoxia can stabilize HIF-1α, a protein that regulates many of genes involved in angiogenesis, erythropoiesis, glycolysis, iron metabolism, and cell survival. One of these genes is Carbonic Anhydrase IX (CA IX). CA IX is an enzyme which maintains pH homeostasis by converting CO2 and H2O into HCO3 - and H+ ions.

The activity of Carbonic Anhydrase in renal tubulus cell can cause an increase of H+ ion in urine. H+ ion must be buffered to prevent its gradient increase that can obstruct H+ secretion. In kidney, NH3 and H+ play an important role to form NH4 +, so secretion of H+ will be continued for pH homeostasis. Glutaminase function in conversion of glutamine into glutamate and NH3 was observed in this study. The samples were obtained from kidney tissues of rat exposed to chronic systemic hypoxia (O2 10% : N2 90%) for 1, 3, 5 and 7 days. Expression of HIF-1α, CA9, and Gls1 mRNA were examined by real time RT-PCR. HIF-1α protein was measured using Cusabio® ELISA, as with the specific activity of CA and glutaminase were measured by spectrophotometer. The maximum levels of HIF-1α and Gls1 mRNA, were achieved in 5 days after hypoxia induction, meanwhile CA9 mRNA expression was found to be the highest at 7 days after induction. HIF-1α protein did not differ significantly among the groups. The maximum CA and glutaminase specific activity was measured at 5 days group. The increase of mRNA and specific activity of both CA and Gls1 in hypoxia shows that both of these protein have an important role for encountering the changing of pH in kidney, especially in the first 5 days. The significant increase of CA9 and Gls1 mRNA is also in line with the increase of HIF-1α mRNA. It can be concluded that expression of CA9 and Gls1 gene is regulated by HIF-1α, although the HIF-1α protein have no difference among the groups."