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Abstrak :
Penyakit hati merupakan masalah kesehatan yang sulit diobati. Adanya masalah dalam pengobatan penyakit ini sebagian disebabkan karena tidak tersedianya obat yang terbukti herkhasiat. Kurkumin, senyawa aktif dalam ke keluarga tanaman curcuma telah diteliti dalam berbagai peyakit termasuk penyakit hati. Efek terapi kurkramin diduga berdasarkan efek antioksidatifnya. Dalam penelitian ini, kami menyelidiki efek kurkumin lerhadap swelling mitochondria yang diinduksi oleh tert-butilhidroperoksida (t-BuOOH) Mitokondria hali diisolasi secara homogen dari tikus Sprague-Dawley (relative specific activity suksinat dehidrogenase adalah 35.73 ±2.78). Pemberian 90 }M t-BuOOH menyebabkan swelling 2 fase yang khas pada mitokondria. Pola swelling dipengaruhi oleh berbagai faktor seperti komposisi bufer, kadar t-BuOOH, jumlah bufer isolasi dan protein mitokondria serta temperatur inkubasi. Swelling dapat dihambat sebesar 85 ±3% oleh kurkumin 2.50 jjM. Pada kadar rendah (1.25 //MJ dan tinggi (5.00 fiM), efek proteksi kurkumin terhadap swelling berkurang (bertitrut-turut 41 ±3% and 77+6%). Swelling dapat terjadi akibat terbukanya mitochondrial transition pore dan dapat mempakan petunjuk awal dan proses kematian sel. Efek inhibisi kurkumin terhadap swelling mitokondria yang diindukxi oleh t-BuOOH diduga disebabkan karena efek antioksidannya. (MedJ Indones 2006; 15:131-6)

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Liver diseases have been a medical problem which is difficult to manage. Some of the problems in the treatment of these diseases lie in the lack of reliable drug available. Curcumin, an active ingredient of the rhizomes of plant Curcuma has been investigated in the treatment of various disorders incuding liver diseases. The therapeutic effects of curcumin on liver diseases have been thought to be associated to its antioxidative properties. In the present study, we investigated the effects of curcumin on mitochondrial swelling in vitro induced by tert-butylhydroperoxide (t-BuOOH). Liver mitochondria were homogeneously isolated from Sprague-Dawley rats (the relative specific activity of succinate dehydrogenase was 35.73 ±2.78). Addition of 90 fj.M oft-BuOOHcauseda typical 2-phase swelling of the mitochondria. The pattern of swelling was influenced by various factors such as buffer composition, concentrations of t-BuOOH, amount of isolation buffer and mitochondrial proteins and incubation temperature.The swelling could be reduced by as much as 85 ±3% by 2.50 uM of curcumin. At lower (1.25 ^M) or higher (5.00 fjM) concentrations, the protection against swelling by curcumin were less effective (respectively were 41 ±3% and 77 ±6%). Swelling might occur due to the opening of mitochondrial transition pore and could be an initial indication in the cascade process leading to cell death. The inhibition of t-BuOOH-induced mitochondrial swelling by curcumin might be because of the antioxidant effects of the compound. (Med JIndones 2006; 15:131-6).

Abstrak :
Kurkumin merupakan senyawa aktif utama dari berbagai Curcuma species. Sudah sejak lama rimpang berbagai Curcuma species seperti Curcuma Longa dan Curcuma xantharrhiza digunakan untuk pengobatan tradisional penyakit hati di Indonesia. Kemampuan kurkumin untuk bekerja sebagai hepatoprotektor telah diteliti secara in vitral dan in vivo. Kurkumin merupakan scavenger radikal bebas oksigen, seperti radikal anion superoksida, radikal hidroksil, dan radikal nitrogen dioksida. Aktifitas antioksidannya ditunjukkan dengan kemampuannya untuk menghambat peroksidasi lipid dalam homogenat otak tikus dan mikrosom hati tikus, serta mencegah deplesi kandungan -SH sel yang ditimbulkan akibat pemberian besi dan butilhidroperoksida tersier. Aktifitas antioksidan kurkumin tersebut dapat memegang peranan penting dalam kemampuannya sebagai hepatoprotektor. Untuk mengerti mekanisme proteksi kurkumin. perlu mengetahui pada tahap manakah proses yang menyebabkan kematian sel dapat dipengaruhi. Walaupun sempat diabaikan cukup lama, saat ini nampaknya mitokondria mempunyai peranan penting dalam kematian sel. baik dalam fisiologi maupun patologi. Akhir-akhir ini perhatian ditujukan pada kemungkinan peranan radikal bebas pada sejumlah penyakit termasuk penyakit hati. Oleh karena itu. penelitian ini dilakukan untuk meneliti efek kurkumin terhadap kerusakan oksidatif mitokondria hati tikus yang terisolasi yang diinduksi oleh butilhidroperoksida tarsier. suatu hidroperoksida organik yang sering digunakan untuk mempelajari stres oksidatif. Efek proteksi kurkurmin di nilai dari hambatannya terhadap swelling mitokondria. kegagalan potensial transmembran mitokondria dan perubahan pola protein mitokondria. Swelling mitokondria diikuti menggunakan spektrofotometer dengan mengukur penurunan absorbans pada 520 nm. Potensial transmembran mitokondria diamati menggunakan spektrofotometer pada dua panjang gelombang yang dinilai dari pergeseran panjang gelombang maksimum dan penurunan absorbans safranin O. yaitu dengan mengukur absorbans pada 516 nm dikurangi absorbans pada 495 nm. Pola protein mitokondria dinilai secara elektroforesis menggunakan SOS-PAGE. Hasil penelitian menunjukkan bahwa butilhidroperoksida tersier menyebabkan kerusakan mitokondria yang dinilai dengan adanya swelling mitokondria; kegagalan potensial transmembran mitokondria dan perubahan pola protein mitokondria yang diamati berupa pembentukan agregat protein dengan berat molekul tinggi dan berkurangnya jumlah kandungan protein pada pita 116 kD sebagai akibat ikatan silang thiol. Kurkumin 2500 µM hampir sempurna mencegah swelling mitokondria dan menghasilkan 85 % proteksi. sementara itu 79 % proteksi terhadap kegagalan potensial transmembran dicapai dengan penambahan kurkumin 250 uM. Kurkumin 3500 uM menghambat pembentukan agregat protein dengan berat molekul tinggi dan menghambat penurunan jumlah protein dengan berat molekul mendekati 116 kD. sebagai akibat adanya hambatan terhadap pembentukan ikatan silang thiol. Hal ini menunjukkan bahwa kurkumin memberikan proteksi terhadap kerusakan Kati oksidatif pada tahap organel mitokondria. ...... The Protective Effects of Curcumin on Swelling, Collapse of Transmembrane Potential, and Alterations of Protein Pattern of Rat Liver Mitochondria Induced by Tert-ButylhydroperoxideCurcumin is a major active compound of several Curcuma species. Many years ago the rhizomes of various Curcuma species like Curcuma Longa and Curcuma xanthorrrizha are used for hepatic diseases in Indonesian traditional medicine. The potential of curcumin to act as hepatoprotector agent has been demonstrated in vitro and in vivo. Curcumin appears to be a potent scavenger of oxygen free radicals, such as super oxide anion radicals. hydroxyl radicals and nitrogen dioxide radicals. Its antioxidant activity has been shown by its capacity to inhibit lipid peroxidation in rat brain homogenates and rat liver microsomes, and by its ability to prevent the depletion of cellular -SH content by iron and tert-butylhydroperoxide. This antioxidant activity of curcumin may play an important role in its hepatoprotective ability. In order to understand the mechanism by which curcumin exerts its protective activity, it is important to know at which levels the process leading to cell death can be influenced. Although neglected for many years. it appears now that mitochondria have a major role on cell death, in both physiology and pathology. Current interest has focused on the possible role of free radicals in a wide range of diseases including hepatic diseases. Therefore, the present study was undertaken to investigate the effect of curcumin on oxidative damage of isolated rat liver mitochondria induced by tert-butylhydroperoxide. an organic hydroperoxide used frequently for studying oxidative stress. The protective effect of curcumin was assessed by studying its ability to inhibit mitochondrial swelling. collapse of mitochondrial Trans membrane potential and alterations of mitochondrial protein pattern. Mitochondrial swelling was followed using spectrophotometer by measuring the decrease of absorbance at 320 rim. Mitochondria] trans membrane potential was observed using a dual-wavelength spectrophotometer by measuring the absorbance of safranin 0 at 316 nm and at 495 nm showing a shift of the maximum wavelength of safranin O and the decrease of its absorbance. Mitochondrial protein pattern was assessed electrophoretically by using SDS-PAGE. The present study showed that tert-butylhydroperoxide caused mitochondrial damage as indicated by mitochondrial swelling, collapse of mitochondrial trans membrane potential. and alterations of protein pattern which were observed as the formation of high molecular mass protein aggregates and the decrease in protein content of 116 kD band due to thiol cross-linking. Curcumin at a concentration of 2500 uM almost completely prevented mitochondrial swelling providing 85 % protection. while 79 % protection against collapse of trans membrane potential was achieved with the addition of 250 uM curcumin. Curcumin at a concentration of 3500 uM inhibited the production of high molecular weight protein aggregates and the decrease of protein with molecular mass close to 116 kD due to inhibition of thiol cross-linking. This indicates that curcumin at concentrations of 250 uM - 3500 uM provided protection against oxidative liver damage at mitochondrial organelle level.