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"Penyakit hati merupakan masalah kesehatan yang sulit di obati.Adanya masalah dalam pengobatan penyakit ini sebagian di sebabkan karena tidak tersedianya obat yang terbukti berkhasiat."

"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)."

"Kurkumin, bahan aktif tanaman kurkuma diduga bermanfaat dalam pengobatan penyakit hati. Dalam penelitian terdahulu, diperlihatkan efek protektif kurkumin terhadap peroksidasi lipid dan swelling mitokondria yang diisolasi dari hati tikus karena pemberian t-butilhidroperoksida (t-BuOOH). Dalam penelitian ini, pemberian t-BuOOH 90 M menyebabkan mitokondria tidak dapat membentuk potensial transmembran (m). Kegagalan pembentukan potential transmembran diduga berhubungan dengan transisi permeabilitas dan apoptosis. Dari 3 dosis kurkumin yang dicoba (0,5 M, 2,5 M dan 5,0 M), ternyata kurkumin dosis 2,5 M dapat mencegah kegagalan pembentukan potensial transmembran akibat t-BuOOH (79,13 + 6,28%). Pemeriksaan elektroforesis protein mitokondria menunjukkan kurkumin 1000 M dapat mencegah agregasi protein yang terjadi akibat t-BuOOH. Dari penelitian ini diperlihatkan efek proteksi kurkumin terhadap kerusakan sistem pembentukan energi dan protein mitokondria yang disebabkan oleh t-BuOOH. (Med J Indones 2007; 16:139-45)

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Curcumin, an active ingredient of curcuma plant has been thought to be beneficial in the treatment of liver diseases. In the previous studies, we have shown the protective effects of curcumin against lipid peroxidation and swelling of the rat liver mitochondrial preparation induced by tert-butylhydroperoxide (t-BuOOH). In the present study, the administration of t-BuOOH of 90 M caused the mitochondria failed to generate a transmembrane potential (m). Of 3 doses of curcumin administered (0.5 M, 2.5 M dan 5.0 M) the maximum protective effect against failure to generate a transmembrane potential caused by t- BuOOH was obtained by 2.5 M of curcumin (79.13 + 6.28%). Further, curcumin of 1000 M could prevent protein aggregation formation caused by t-BuOOH in the electrophoretogram. This study shows the protective effects of curcumin against damaged of energy production system and protein of the mitochondria caused by t-BuOOH. (Med J Indones 2007; 16:139-45"

"A three-lever logistics service supply chain (LSSC) consisting of a logistics service integrator (LSI), a logistics service provider (LSP), and a functional logistics service subcontractor (LSS) is discussed in this paper. Since the improvement of logistics service levels caused by the effort of LSS can significantly effect the market demand for LSSC, a dynamic game theory model is developed to solve the coordinating contract design problem in this condition. A joint contract is between LSI and LSP, which are regarded as a whole to share revenue and cost with LSS in the two transactions of LSSC. The reasonable choice of parameters can attain the maximum of the expected profit of LSSC and the win-win good among all members, finally, a corresponding numerical example is presented to illustrate the conclusions."

"Ruang lingkup dan cara penelitian: Kurkumin adalah salah satu zat aktif dari tanaman kurkuma yang banyak terdapat di Indonesia dan sudah lama digunakan sebagai obat, diantaranya untuk penyakit hati. Penelitian kurkumin sebagai hepatoprotektor sudah banyak dilakukan, namun mekanismenya belum diketahui dengan jelas. Beberapa hasil penelitian in vivo pada tikus dan mencit maupun in vitro dengan menggunakan mikrosom hati dan hepatosit tikus, menunjukkan bahwa kurkumin efektif sebagai antioksidan, menghambat enzim sitokrom P450, siklooksigenase dan lipooksigenase serta menghambat proses peroksidasi lipid.Penelitian ini dilakukan untuk mendapatkan informasi tentang mekanisme kerja kurkumin sebagai hepatoprotektor, dengan mempelajari efek kurkumin pada mitokondria hati tikus (galur Wistar) terisolasi, menggunakan t-BuOOH sebagai model untuk menimbulkan cedera oksidatif. Isolasi mitokondria dilakukan dengan cara sentrifugasi bertingkat. Fraksi mitokondria yang diperoleh dibagi 4 bagian, masing-masing untuk pengukuran aktivitas enzim suksinat dehidrogenase (SDH) dan sitokrom c oksidase (CCO), kadar glutation (GSH) dan malondialdehid (MDA). Tiap bagian dibagi 9 kelompok. Dalam pengukuran tersebut mitokondria diinkubasi pada suhu 37° C selama 30 menit, dengan atau tanpa penambahan t-BuOOH, dan dengan atau tanpa pemberian kurkumin. Pengukuran ke empat parameter dilakukan secara spektrofotometri pada panjang gelombang 600 nm (untuk SDH), 550 nm (untuk CCO), 412 nm (untuk GSH), dan 530 nm (untuk MDA).Hasil dan kesimpulan: Mitokondria diisolasi cukup baik (RSA untuk SDH = 32.59 dan untuk CCO = 72.18). Penambahan t-BuOOH pada mitokondria terisolasi mengakibatkan deplesi GSH (78 %) yang diikuti oleh peningkatan kadar MDA (125 %), penurunan aktivitas SDH (20 %), dan CCO (22 %). Perubahan ini dapat dihambat oleh kurkumin pada dosis berbeda. Pada dosis 500 RM, kurkumin dapat meningkatkan kadar GSH (50 %) disertai dengan penurunan kadar MDA (45 %), namun tidak diikuti oleh peningkatan aktivitas SDH dan CCO, mungkin dosis ini merupakan dosis toksik untuk enzim SDH dan CCO. Peningkatan aktivitas SDH (23 %) dan CCO (20 %) terlihat pada dosis 5 RM. inkubasi mitokondria mengakibatkan penurunan aktivitas SDH dan CCO dan peningkatan kadar GSH dan MDA, dimana kurkumin tidak mampu melindungi perubahan tersebut, kecuali untuk MDA. Meskipun GSH tidak terlibat langsung pada kegiatan respirasi mitokondria, namun GSH sangat berperan dalam mengontrol ststus redoks di mitokondria serta memelihara integritas membran melalui perlindungan gugus SH protein di membran. Hasil penelitian ini memperlihatkan bahwa kurkumin dapat mencegah kerusakanl gangguan fungsi mitokondria pada rentang dosis 5 - 500 W.

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Field and methodology : Curcumin is an active substances of Curcuma, a plant which is abundantly found in Indonesia. and has traditionally been used as herbal medicine, for instance for liver diseases. There have been many studies carried out on cm-cumin as a hepatoprotective agent. However, the mechanism underlying the protective effects are not known. Some in vivo studies on rate and mice as well as in vitro studies using rat liver microsomes and hepatocytes, showed that cu-cumin is an effective antioxidant, that it causes inhibition of cytochrom P450, cyclooxygenase and lipooxygenase activities and lipid peroxidation . The present study was performed to find out some information on the mechanism of action of curcumin as a hepatoprotective agent, using isolated mitochondria from rat (Wistar) liver as a model and t BuOOH as an oxidative inducing --- agent. The liver mitochondria were isolated using differential cenirifiugatien_.On the isolated mitochondria. was determine the activities of succinate dihydrogenase (SDH) and cytochrome a oxidase (CCO) and the contens of reduced glutatione (GSH) and malondialdehyde (MDA). In each determination mitochondria) fractions were incubated at 37°C for 30 min, in the presence and absence of t-BuOOH, and with or without cm-cumin. The biochemical parameters were determined spectrophtometrically at 600 nm (SDH), 550 um (CC 0), 412 nm (GSH), 530 um (MDA).

Results and conclusion : The mitochondria was purified to high degree (RSA for SDH and CCO, respectively were 33 and 72). The protein yield was 43 mgfg liver wet weight. The addition of t-BuOOH on isolated mitochondria caused GSH depletion (78 %) and increase MDA (125 %) and decrease activites of SDH (20 %) and CCO (22 %). The biochemical alteration could be inhibited by cm-cumin at various concentrations. At 500p.M, cm-cumin could increase GSH level (50 %) and decrease MDA (45 %), but could not increase the activities of SDH and CCO; it appeared that at the concentration cm-cumin was toxic for SDH and CCO. Increase activity of SDH (23 %) and CCO (20 %) was found at the concentration of 51A.M of curcumin. Incubation of mitochondria alone cause decrease activities of SDH and CCO and increase of level GSH and MDA, whereas cm-cumin had no protection, except on MDA level. Although GSH is not directly involved in the activity of mitochondria! respiration, this peptide play a significant role in controlling the redox status of the mitochondria and preserving the membrane integrity through maintaining the thiol contents in the membrane protein. This study demonstrates the protective effects of curcurnin wind oxidative damage of the liver mitochondria in the range of 5 - 500 µM"

"Pengaruh pencegahan Vitamin A terhadap sifat-sifat karsinogenik dan toksik yang diinduksikan oleh Dimethylnitrosamine (DMN) terhadap hati tikus, telah diteliti melalui 2 (dua) pendekatan: pendekatan tes karsinogenitas dan pendekatan tes toksisitas subakut. Pada penelitian pangaruh karsinogenitas DMN dalam tes prakarsinogenisitas, telah dipergunakan 60 (enam puluh) ekor tikus putih percobaan betina dari Lembaga Makanan Rakyat (LMR), masing-masing berumur satu bulan.Berdasar penemuan dalam penelitian pendahuluan, Vitamin A diberi selama satu minggu sebelum dan delapan minggu selama pemberian dosis DMN. Dosis efektif Vitamin A yang dipergunakan sebesar 3,000 S.I./tikus secara berseling hari,dengan memasukkannya langsung ke dalam mulut tikus, sedangkan DMN diberikan pada dosis 30 ppm (mg per kg air), dilarutkan dalam air minum secara bebas (ad libitum). Hasil penelitian menunjukkan bahwa DMN menurunkan konsumsi air minum dan makanan pada tikus-tikus percobaan dan DMN, seperti juga sebagian besar jenis bahan beracun lain, dapat menurunkan kecepatan tumbuh dari tikus percobaan tersebut, sedangkan Vitamin A dapat mengurangkan tingkat pengaruh dari DMN itu.DMN juga memberikan retensi air di dalam hati tikus dan meningkatkan berat basah dari hati dan ginjal binatang-binatang tersebut. Tikus yang diberi DMN and Vitamin A memperlihatkan peningkatan berat hati.Penelitian fungsi hati: Tikus-tikus yang diberi DMN dengan tanpa Vitamin A memperlihatkan kadar Amino transferase aspartat (AST - Aspartate Amino Transferase) Amino transferase Y-glutamat (GGT - Y! Glutamyl Amino Transferase), dan Triglycerida (TG) dalam batas-batas normal, tetapi kadar Phosphatase lindi (AP - Alkaline Phosphatase) meningkat dua kali lipat, sedangkan kadar protein (albumin) terdapat pada tingkat dalam tingkat normal.Pada kelompok yang diberi DMN bersamaan dengan Vitamin A, pada satu minggu pemberian DM, Vitamin A memberikan pengaruh terhadap induksi aktivitas Damethylase DMN, bila Vitamin A itu diberikan sebelum atau berbareng dengan pemberian DMN, tetapi pengaruh tersebut tidak tampak bila Vitamin A setelah pemberian DMN.Penelitian di bawah mikroskap memperlihatkan bahwa kelompok-kelompok tikus yang diberi DMN dengan atau tanpa Vitamin A tidak memberikan gambaran hati yang berbeda secara makna statistik, bila diberi DMN untuk satu minggu, tetapi bila pemberian DMN dilakukan untuk waktu lebih lama, yaitu untuk 2 (dua) minggu, terlihat perbedaan pada gejala-gejala toksik yang didukung oleh hasil yang terdapat pada penelitian prakarsinigenisitas (diberi DMN) untuk selama 8 (delapan) minggu. Penelitian makroskopik maupun mikroskopik tidak memperlihatkan pertumbuhan yang bermakna pada ginjal tikus-tikus percobaan tersebut. Vitamin A mempunyai pengaruh melindungi melawan sifat karsinogenisitas dan toksisitas terhadap hati tikus percobaan yang diinduksi oleh DMN dalam dua cara: yang pertama melalui penghambatan bersaring terhadap enzim-enzim mikrosoma dan memblokade tingkat penting dari proses pengaktifan DI1N, dan yang kedua melalui peningkatan respons immunologik dari tikus-tikus percobaan itu terhadap benda-benda asing, penyakit-penyakit dan termasuk pula terhadap sel-sel hati yang mengalami perubahan pada masa proses proleferasi dan multiplikasi. Dan Vitamin A mempunyai juga pengaruh yang menghambat, terhadap peningkatan dari kegiatan Demethylase DMN yang bersangkutan dengan proses penggiatan metabolik dari DMN tersebut. Dengan singkat dapat dikatakan bahwa Vitamin A dapat menghindarkan pengaruh DMN sebagai bahan toksik dan karsinagenik terhadap hati tikus, meskipun tidak secara mutlak.

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The preventive effect of vitamin A on carcinogenicity and toxicity induced by dirnethylnitrosamine (DIN) on rat livers was studied through 2 tests, precarcinogenicity test and sub acute toxicity test.To study on carcinogenic effect of DMN in the precarcinogenicity test, 60 albino female Lembaga Makanan Rakyat (LMR) Rats with the age of one-month were used.Based on the preliminary study of this experiment vitamin A was given 1 week before and 8 weeks during DMN treatment. The effective dosage of vitamin A given was 3,000 IU'rat alternate days by dropping into the mouth and the DMN at a dosage of 30 ppm through drinking water adlib. The results show that DM decreases water and food consumption of experimental rats and DMN, like most toxic agents, can decrease growth rate of experimental rats and that vitamin A can decrease the degree of this toxic effect induced by DM.N. DMN also causes water retention in the rat livers and kidneys causing weights increase.In the DMN and vitamin A treated rats liver weights have also increased, Liver function tests show that serum levels of aspartate amino transferase (AST), glutamyl amino transferase (GGT) and triglyceride (TG) of the DMN with/without vitamin A treated rats are in the normal values, but alkaline phosphates (AP) levels rise 2-fold, and protein (albumin) levels are significantly low.In the DMN and vitamin A treated rats globulin levels are high, and DIN demethylase activity of the liver is also increased.Macroscopic findings show that 18 out of 20 rats in the DMN treated group developed red discolored lesions of the livers, but only 6 out of 19 rats in the DMN and vitamin A treated group. It also shows that 10 out of 20 rats of DMN treated group developed hepatocyte nodules but no nodules were found in the DMN and vitamin A treated group. Macro and Microscopic findings show no significant changes of the kidneys."

"Adaptation mechanism to hypoxia in living organisms increases reactive oxygen species (ROS) formation that could exceed the capacity of anti oxidant. Gluthatione (GSH) in which highest concentration present in liver, plays an important role in maintaining the intracellular redox equilibrium and protect tissues from oxidative stress. The aim of this study was to observe tissue response of rat that was exposed to chronic systemic hypoxia by analyzing the oxidative stress in liver tissue. Twenty male Sprague-Dawley rats were induced by chronic systemic hypoxia by kept them in hypoxic chamber (10% O2:90% N2) for 1, 3, 7 and 14 day(s). All rats were sacrificed with ether anesthesia after hypoxia treatment. Liver tissues were analyzed using parameters of oxidative stress, malondialdehyde (MDA) with tBARS test, and endogenous antioxidant, glutathione reduced form (GSH). The study showed that chronic systemic hypoxia induction caused oxidative stress in liver tissue, which was shown by increased concentration of MDA in liver tissue (nmol/mg liver tissue). Concentration of MDA in liver tissue was increased significantly on day-1, day-3, day-7 and day-14 compared to control group (ANOVA, LSD, p<0.05). The differences between day-3, day-7 and day-14 was not significant. In contrast, liver GSH content (μg/mg liver protein) was progressively decreased significantly since day-1 of hypoxia until the end of experiment (ANOVA, LSD, p<0.05). Statistical analysis revealed that there is a strong correlation between MDA and GSH concentration in liver tissue (Pearson = - 0.993). It was concluded that oxidative stress present in liver tissue of rat induced by chronic systemic hypoxia."

"Latar Belakang: Berbagai penelitian terdahulu telah membuktikan bahwa kurkumin memiliki sifat hepatoprotektif sehingga memungkinkannya untuk mengobati banyak jenis penyakit hepar. Meskipun kurkumin aman dan mempunyai banyak aktifitas biologis, penggunaan kurkumin belum dapat digunakan secara komersil sebagai obat terapeutik karena tingkat absorbsi, stabilitas, dan bioavailabilitas yang rendah serta metabolisme kurkumin yang cepat. Berhubung studi mengenai efek pengurangan ukuran partikel untuk meningkatkan distribusi jaringan belum dilakukan sepenuhnya, penelitian ini bertujuan untuk mengetahui apabila peningkatan konsentrasi kurkumin di jaringan hepar dapat dilakukan dengan menggunakan nanopartikel.Metode: Penelitian ini merupakan penelitian in vivo pada tikus. Tikus dirandomisasi menjadi 2 kelompok, masing-masing 5 ekor yang mendapatkan kurkumin konvensional 500 mg/kgBB atau nanokurkumin 500 mg/kgBB dosis tunggal secara oral. Sampel hati diambil setelah 3 atau 4 jam setelah pemberian obat dan konsentrasi kurkuminnya dikuantifikasi menggunakan UPLC-MS/MS.Hasil: Konsentrasi nanokurkumin lebih tinggi daripada konsentrasi kurkumin konvensional di jaringan hepar setelah 3 jam dan relatif lebih tinggi setelah 4 jam. Pada 3 jam, konsentrasi rerata nanokurumin (33.1934 ng/mg) adalah lebih dari 7 kali lipat dibandingkan konsentrasi rerata kurkumin (4.5189 ng/mg) dan bermakna secara statistik (p = 0.047). Pada 4 jam, konsentrasi rerata nanokurumin (11.8725 ng/mg) hanya sedikit lebih tinggi dibandingkan konsentrasi rerata kurkumin (11.6352 ng/mg) dan tidak bermakna secara statistik (p = 0.251).Konklusi: Pemberian nanokurkumin secara oral menghasilkan konsentrasi kurkumin yang lebih tinggi di hati tikus setelah 3 dan 4 jam daripada kurkumin konvensional.Background: Many previous researches have proven that curcumin possesses potent hepatoprotective propertiy which enables it to treat and prevent the progression of different hepatic disorders. However, despite its superior safety profile and biological activity, curcumin has not been commercially used as a therapeutic drug due to its extremely poor absorption and stability, low bioavailability and rapid metabolism. As the effect of decreasing its particle size to improve its tissue distribution have yet to be studied thoroughly, this research aims to find out if higher curcumin concentrations in liver tissue can be achieved by using nanoparticles.Method: This research is an in vivo research in rats. The rats are randomized into 2 groups, each with 5 rats which were given either single doses of 500 mg/kgBW conventional curcumin or 500 mg/kgBW nanocurcumin orally. The liver samples were obtained after 3 or 4 hours, followed by curcumin concentration measurement using the UPLC-MS/MS method. Results: Nanocurcumin concentrations were higher than curcumin concentrations in the liver tissue at 3 hours and relatively higher at 4 hours. At three hours, the mean nanocurcumin concentration (33.1934 ng/mg) is over 7 times higher than mean curcumin concentration (4.5189 ng/mg) and is statistically significant (p = 0.047). At 4 hours, the mean nanocurcumin concentration (11.8725 ng/mg) is slightly higher than mean curcumin concentration (11.6352 ng/mg) not statistically significant (p = 0.251)Conclusion: Oral administration of nanocurcumin results in higher curcumin concentrations in rat liver tissue after 3 and 4 hours compared to conventional curcumin."

"Alkohol merupakan senyawa yang paling sering disalahgunakan (abuse), dan akhirnya menimbulkan berbagai permasalahan, bukan hanya di bidang kesehatan, melainkan juga di bidang sosial dan ekonomi, di seluruh dunia. Hati merupakan salah satu organ yang paling banyak dipengaruhi oleh toksisitas etanol. Hepatotoksisitas intrinsik etanol timbul akibat oksidasi etanol oleh enzim alkohol dehidrogenase (ADH) dan sistem enzim yang mengoksidasi etanol di mikrosom (MEOS), yang terutama melibatkan CYP2E1. Metabolit toksik etanol (akibat oksidasi etanol oleh ADH dan CYP2E1), yaitu asetaldehid, serta induksi aktivitas CYP2E1 akibat pemberian etanol kronik, dapat meningkatkan stres oksidatif terutama pada mitokondria, yang merupakan organel target intoksikasi alkohol. Styes oksidatif yang mengakibatkan gangguan fungsi mitokondria, mengawali berbagai gangguan metabolik maupun aktivasi sistem makrofag hepatik, yang akhimya menuju kematian sel hati (hepatosit), balk secara nekrosis ataupun apotosis; dan dianggap memainkan peranan panting dalam patogenesis dan progresi penyakit hati alkoholik. Oleh karena itu, antioksidan dapat menjadi salah satu terapi yang potensial dalam penanganan penyakit had alkoholik di masa mendatang. Likopen, sebagai salah satu senyawa karotenoid non pro-vitamin A yang memiliki aktivitas antioksidan yang sangat kuat, secara in vide terbukti dapat mencegah sties oksidatif pada mitokondria dan apoptosis yang diinduksi oleh etanol pada kultur set HepG2 yang mengekspresikan CYP2E1. Namun demikian, sampai scat ini belum ada penelitian yang mengkonflr nasi efek protektif likopen in vivo terhadap gangguan fungsi mitokondria akibat stres oksidatif oleh pemberian etanol kronik. Penelitian ini merupakan penelitian in vivo yang menggunakan model hewan untuk mempelajari hal tersebut. Model hewan yang digunakan adalah tikus jantan (120-180 g), strain Sprague Dawley. Hewan uji dibagi ke dalam 6 kelompok @ 4 ekor. Diet standar untuk tikus yang diperoleh dari Badan POM, Jakarta, diberikan ad libitum. Untuk menimbulkan induksi gangguan fungsi mitokondria, pemberian etanol dilakukan pada tikus percobaan dilakukan selama 4 minggu, dengan dosis 1 mL etanol 25%I100 g BB. Suplementasi likopen diberikan dalam 3 dosis yang berbeda (masing-masing 25, 50 dan 100 mg/kg BB/hari) dan dimulai sejak 2 minggu sebetum pemberian etanol kronik, dan tetap dilanjutkan selama etanol diberikan. Tikus dimatikan dengan dislokasi leper, dan segera dilakukan isolasi mitokondria. Stres oksidatif dan gangguan fungsi mitokondria akibat pemberian etanol kronik pada tikus dikuantifikasi menggunakan beberapa parameter, seperti: tingkat peroksidasi lipid (kadar MDA) mitokondria dan homogenat had, kadar GSH mitokondria (mGSH), dan aktivitas beberapa enzim mitokondria, seperti suksinat dehidrogenase dan NADH-sitokrom c oksido-reduktase serta FO-Fl-ATPase. Pengukuran parameter-parameter tersebut dilakukan dengan metode spektrofotometri menggunakan cahaya visibel (kolorimetri).Mitokondria diisolasi dengan kemumian sedang (RSA SDH = 11.01). Dibandingkan dengan kelompok kontrol, pemberian etanol kronik secara bermakna meningkatkan stres oksidatif pada mitokondria, yang ditunjuklcan oleh peningkatan kadar MDA mitokondria (100%) maupun homogenat hati (55%), serta penurunan kadar mGSH (30%) dan rasio GSH/GSSG mitokondria (40%). Pemberian etanol kronik juga menyebabkan gangguan fungsi mitokondria, seperti menurunkan SA SDH mitokondria (40%), meningkatkan aktivitas NADH-sitokrom c oksido-reduktase (76%) dan meningkatkan aktivitas hidrolisis F1-ATPase (30%). Enzim NADH-sitokrom c oksido-reduktase tidak sensitif terhadap inhibitor rotenon. Pemberian rotenon hanya sedikit meningkatkan atau tidak mempengaruhi aktivitas enzim tersebut, dan tidak mengubah perbandingan aktivitas enzim anlar kelompok. Enzim FI-ATPase sens"itif terhadap inhibitor oligomisin. Pada kelompok etanol kronik, pemberian oligomisin menurunkan aktivitas enzim FO-FI-ATPase sebesar 82%. Nilai ini lebih tinggi secara bermakna dibandingkan dengan penurunan akitivitas pada kelompok kontrol (72%). Suplementasi likopen pada ketiga dosis yang diberikan mampu mengembalikan aktivitas SDH, NADH-sitokrom c reduktase, kadar MDA mitokondria dan homogenat hati, serta kadar mGSH, sampai setara dengan kelompok kontrol. Peningkatan dosis Iikopen tidak menimbulkan perbedaan berrnakna pada parameter-parameter tersebut. Namun demikian, hanya likopen dosis 100 mg/kg BB/hari yang dapat mengembalikan rasio GSH/GSSG, aktivitas hidrolisis FOFI-ATPase dan sensitivitasnya terhadap oligomisin, sampai setara dengan kelompok kontrol. Secara umum dapat disimpulkan bahwa likopen memiliki efek proteksi terhadap gangguan fungsi mitokondria hati tikus akibat pemberian etanol kronik. Namun demikian, suplementasi likopen tanpa induksi gangguan fungsi mitokondria tidak memperlihatkan manfaat yang berarti.

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Alcohol is the most frequently abused substance worldwide, which will eventually bring about lots of health, social and economical problems. Of many other organs, alcohol exerts its toxicity mostly in the liver. Ethanol intrinsic hepatotoxidty results mainly from its oxidation by alcohol dehydrogenase (ADH) and microsomal ethanol oxidizing system (MEOS) which involves mainly CYP2E1. Acetaldehyde, a toxic metabolite of ethanol (results from its oxidation by ADH and CYP2E1), and the induction of CYP2EI enzyme due to chronic alcohol consumption will raise oxidative stress on mitochondria, the target organelle of ethanol intoxication. Oxidative stress, which results in mitochondria) dysfunction, initiates various metabolic disorders, activates hepatic macrophageal system, and contributes to enhanced cell death, either by apoptosis or necrosis. Mitochondrial oxidative stress plays a critical role in the pathogenesis and progression of alcoholic liver disease (ALD). Hence, antioxidants may be a potential therapy in the future management of ALD. To date, lycopene, a non-provitamin A carotenoid with a potent antioxidant activity, attenuated mitochondrial oxidative stress and ethanol-induced apoptosis in HepG2 cell expressing CYP2EI. Yet, there has no in vivo study been done in order to confirm the protective effect of lycopene against mitochondrial dysfunction due to chronic ethanol intake. Thus, the current in vivo study was designed to answer -at least partly- the question. The animal models used were male Sprague Dawley rats (120-180 g), which were divided into 6 groups @ 4 rats. Standard diet for rodents, produced by BPOM, Jakarta, was administered ad libitum every day. Ethanol at a concentration of 25%v/v (1 mL/100 g BW) was administered orally for 4 weeks, in order to induce mitochondrial injury. Lycopene supplementation was given orally in 3 dosage regimens, 25, 50 and 100 mg/kg BW/ day, since 2 weeks before and continued for 4 weeks during ethanol treatment. The rats were all terminated by cervical dislocation and then mitochondrial isolation was performed immediately. The ethanol-induced oxidative stress and mitochondria) injury were quantified by measuring the following parameters: degree of lipid peroxidation (mitochondria) and liver homogenate MDA levels), mitochondria) GSH level (mGSH) and the activity of some mitochondrial enzymes, such as sucdnate dehydrogenase, NADH-cytochrome c oxido-reductase, and FO-F1-ATPase. All parameters were measured by using the method of visible spectrophotometry (colorimetry).The liver mitochondria was adequately purified (RSA SDH = 11.01). Compared to the control group, chronic ethanol treatment significantly increased mitochondria) oxidative stress, as exhibited by the increased levels of mitochondria) and liver homogenate MDA (by 100% and 55%, respectively), depressed level of mGSH (by 30%) and lowered ratio of mitochondrial GSH/GSSG (by 40%). Chronic ethanol treatment also induced mitochondria) dysfunction, as measured by the reduced specific activity of mitochondria) SDH (by 40%), increased activity of NADH-cytochrome c oxido-reductase (by 76%), and increased hydrolysis activity of FO-F1-ATPase (by 30%). NADH-cytochrome c oxido-reductase was insensitive to rotenone, as addition of the inhibitor to the reaction mixture slightly increased or did not affect the enzyme activity, nor changed the ratio of its activity between groups. FO-FI-ATPase was sensitive to oligomycin. In chronic ethanol group, addition of oligomydn to the reaction mixture reduced the enzyme activity by 82%, which was significantly greater than the reduction showed by control group (72%). Lycopene supplementation was able to normalize the activity of SDH, NADH-cytochrome c oxido-reductase, the levels of mitochondrial and liver homogenate MDA and mGSH level, back to the levels of control group. Higher doses of lycopene did not provide significantly better results to those parameters. However, only the highest dose of lycopene (100 mg of /kg BW/day) could normalize mitochondria) GSH/GSSG ratio, the activity of FO-FIATPase and its sensitivity to oligomydn to the levels of control group. Generally, this study concluded that lycopene has protective effect against ethanol-induced hepatic mitochondria) injury in rats. However, without ethanol-induced mitochondrial injury, lycopene supplementation does not provide any additional benefit."

"Keadaan hipoksia menyebabkan peningkatan Hypoxia Inducible Factor (HIP) sebagai respon terhadap menurunnya kadar oksigen. Selain menyebabkan peningkatan HIP, hipolsia juga menyebabkan peningkatan pembentukan dan penglepasan Reactive Oxygen Species (ROS) dari dalam mitokondria. yang kemudian akan meregulasi respons terhadap 02 yang rendah. Akibat peningkalan pembentukan ROS, kcmungkinan dapat teijadi stres oksidatif Penelitian ini bertujuan untuk mempelajari dan mengamati pengaruh hipoksia sistemik terhadap ekspresi gen HIF I-a dan stres oksidatif pada jaringan hati tikus yang diindiksi hipoksia sistemik selama I, 3, 7 dan 14 hari yang dibandingkan dengan kelompok normoksia sebagai kontrol.Induksi hipoksia sistemik dilakukan dengan memaparkan tikus jantan Sprague-Dawley terhadap lingkungan dengan oksigen l0% dan nitrogen 90% dalam sungkup hipoksiai Kada: protein, glutatzion (GSH) dan malondialdehid (MDA) diperiksa dari homogenat hati likus. Kadar protein dihitung dengan mengukur serapan pada 1 280 nm dan dibandingkan dengan serapan larutan standar Bovine Serum Albumin. Kadar malondialdehid (MDA) ditetapkan dengan metode Wiils dan kadar glutation (GSH) diukur dengan rnetode Ellman. Analisis ekspresi gen HIF 1-a dilakukan dengan metode Wesrern Blot dengan menggunakan anti HH? l-oi sebagai antibodi primer, anti IgG mouse sebagai antibodi sekunder dan pewamaan menggunakan aminoerhyl carbazole.Hasil penelitian menunjukkan bahwa kadar MDA hati meningkat mulai hari ke-l hipoksia dan bertahan sampai I4 hari, walaupun tidak bemiakna secara statistik Kadar GSH hati menunjukkan penutunan yang bermakna seiring dengan lamanya hipoksizi Hasil Weslerrz Blot menunjukkan adanya HIP I-a pada normoksia, hipoksia 1 hari dan 3 hari. Dapat disimpulkan bahwa terjadi stres oksidatif di jaringan hati seiring dengan lamanya hipoksia.

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Hypoxia condition increases the level of hypoxia-inducible factor (HIF) as response to oxygen deprivation. Hypoxia also increases production and releases of reactive oxygen species (ROS) from mitochondria Excessive production of ROS can lead to oxidative stress, due to its reactivity with macromolecules within cell, ie lipid. The objective of this study is to observe the effects of induction of systemic hypoxia on expression of HIP 1-c. gene and its relation oxidative stress in rat liver tissue.

The experiment was conducted on 25 male Sprague-Dawiey rats, which were divided into 5 groups : normoxic, hypoxia for l day, 3 days, 7 days and 14 days. Induction of systemic hypoxia was carried by exposing the rats in a hypoxic chamber with environment 10% 02 and 90% N2. To asses the oxidative stress condition, malondialdehyde (MDA) and glutation (GSH') concentration in liver was measured using Wills? and Ellman?s method, respectively. Expression of HIP 1-ot gene was analyzed using Westem Blot.

The result showed that MDA concentration is higher in all hypoxic group with no statistically significance difference. The GSH level decreased significantly until day 14. It seemed that oxidative stress occurred at day 14. HIF 1-a was expressed in normoxic condition, hypoxia day l and day 3. It was concluded that oxidative stress was more likely to occur at day 14 of hypoxia."