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Abstrak :
Latar Belakang: Kurkumin diketahui sebagai antiinflamasi, antioksidan, antiproliferatif, dan antiangiogenik, sehingga menjadi salah satu alternatif terapi diabetes tipe 2 dengan menghambat progresifitasnya. Dengan sediaan nanopartikel availibilitasnya semakin meningkat. Penelitian ini dilakukan untuk melihat adanya efek nanokurkumin terhadap komplikasi diabetes melitus khususnya kardiomiopati yang dinilai dengan ekspresi mRNA B-type natriuretic peptide BNP pada jaringan jantung. Metode: Penelitian ini menggunakan jaringan tersimpan dari penelitian yang telah dilakukan sebelumnya. Jaringan kemudian dibuat menjadi cDNA dari sintesis isolasi RNA jaringan jantung tikus. Diabetes tipe 2 pada tikus dibuat dengan menginjeksikan streptozotocin dan nicotinamide. Nanokurkumin diberikan dalam dosis 100mg/kgBB/hari selama 30 hari. Tingkat ekspresi mRNA BNP-45 diukur dengan qRT-PCR dan dihitung dengan metode Livak. Hasil: Terdapat peningkatan ekspresi mRNA BNP-45 pada kelompok DM terhadap kelompok normal. Pemberian nanokurkumin sebanyak 100mg/KgBB selama 30 hari pada kelompok DM NK menghasilkan rasio ekspresi mRNA BNP-45 lebih rendah secara statistik terhadap kelompok DM. Kesimpulan: Nanokurkumin dapat menekan ekspresi mRNA BNP-45 pada jantung tikus yang diinduksi streptozotocin dan nicotinamide pada tingkat dosis 100mg/kgBB/hari selama 30 hari. ...... Background: Curcumin is known as anti inflammatory, antioxidant, antiproliferative, and antiangiogenic. Therefore it is promising to become alternative treatment of type 2 diabetic by inhibiting its progressiveness. From previous study, it was reported that bioavailability of curcumin increases in form of nanoparticles. This study was conducted to see the effect of nanacurcumin on cardiomyopathy assessed by the expression of B type natriuretic peptide BNP mRNA in heart tissue. Method: This experimental study used stored tissue from previous research. Then the tissue changed to cDNA from RNA isolation synthesis of rats heart tissue. The type 2 diabetic in rat was induced by streptozotocin and nicotinamide. Nanocurcumin was given orally at the dose 100mg kgBW day for 30 days. The expression level of BNP 45 mRNA was measured by qRT PCR and calculated by the Livak method. Result: There was an increased ratio of expression of BNP 45 mRNA in the DM group against the normal group. Nanocurcumin 100mg KgBB administered orally for 30 days in the DM NK group resulted in a statistically lower ration of BNP 45 mRNA expression than the DM Group. Conclusion: Nanocurcumin may suppress expression of BNP 45 mRNA in the heart of rats induced streptozotocin and nicotinamide at a dose level of 100 mg kgBW day for 30 days.

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ABSTRAK Latar Belakang: Endoksifen merupakan terapi baru pada pengobatan sel kanker payudara yang responsif terhadap endokrin. Studi terdahulu menunjukkan bahwa paparan endoksifen jangka panjang dapat menyebabkan resistensi melalui mekanisme Epithelial-Mesenchymal Transition (EMT). EMT adalah sebuah proses dimana suatu sel epithelial berubah menjadi sel mesenkimal. Proses EMT ditandai dengan adanya modulasi marker-marker epitelial seperti E-cadherin, vimentin dan TGF-β1. Berbagai penelitian telah menunjukan bahwa paparan singkat kurkumin dapat memperbaiki marker-marker EMT. Namun, kurkumin memiliki keterbatasan karena bioavailabilitasnya yang rendah. Oleh karena itu, pada penelitian ini kami menggunakan nanokurkumin untuk mencegah jalur EMT. Metode: ini merupakan penelitian in vitro menggunakan sel MCF-7. Kami membagi sel menjadi beberapa kelompok yaitu: Endoksifen 1000 nM+β-estradiol 1 nM, Endoksifen 1000 nM+β-estradiol 1 nM + nanokurkumin (8.5 μM dan 17 μM), Endoksifen 1000 nM+β-estradiol 1 nM+kurkumin 17 μM dan DMSO selama 8 minggu. Sel kemudian dipanen dan dihitung setiap minggu. Setelah minggu ke-4 dan ke-8 paparan, ekspresi E-cadherin, TGFβ1 dan vimentin diukur menggunakan two-step qRT PCR. Pada minggu ke-8, kadar protein TGF-β1 diukur dengan ELISA, sementara morfologi sel MCF-7 diamati menggunakan mikroskop konfokal. Hasil: Terdapat peningkatan viabilitas sel pada kelompok Endoksifen 1000 nM+β-estradiol 1 nM. Viabilitas sel menurun secara signifikan pada kelompok nanokurkumin dan kurkumin 17 μM, tetapi tidak pada kelompok nanokurkumin 8.5 μM. Analisis marker EMT pada minggu ke-8 menunjukkan terdapat peningkatan ekspresi mRNA vimentin dan TGF-β1 sementara ekspresi mRNA E-cadherin dan kadar protein TGF-β1 tampak menurun. Hasil menunjukkan bahwa pemberian nanokurkumin pada semua dosis tidak mampu memperbaiki ekspresi vimentin, TGF-β1, dan E-cadherin. Tidak tampak perbedaan yang signifikan antara nanokurkumin dan kurkumin terhadap modulasi marker-marker EMT pada sel kanker payudara yang dipaparkan endoksifen berulang. Pengamatan morfologi menggunakan mikroskop konfokal menunjukkan adanya sel mesenkimal baik pada kelompok endoksifen+β-estradiol maupun kelompok yang mendapat nanokurkumin/kurkumin. Kesimpulan: nanokurkumin tidak mampu mencegah aktivasi EMT walaupun dapat menurunkan viabilitas sel pada penggunaan jangka panjang. Meskipun nanokurkumin lebih terakumulasi di dalam sel. tidak tampak perbedaan potensi dibandingkan dengan kurkumin dalam menurunkan marker EMT.

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ABSTRACT Background: Endoxifen is a novel therapy in the treatment of endocrine responsive type of breast cancer. Previous study showed that long-term exposure of endoxifen may lead to resistance through the mechanism of Epithelial-Mesenchymal Transition (EMT). EMT is a process where epithelial cells turn into mesenchymal cells. EMT is characterized by the modulation of epithelial markers such as E-cadherin, vimentin and TGF-β. Various studies have shown that short term treatment with curcumin may improve EMT markers. However, the efficacy of curcumin is limited by its low bioavailability. In this study, we use nanocurcumin to prevent the activation of EMT. Methods: This is an in vitro study in MCF-7. We exposed the cells to several groups, which are: endoxifen 1000nM + β-estradiol 1 nM, endoxifen 1000nM + β-estradiol 1 nM + nanocurcumin (8.5 μM and 17 μM), endoxifen 1000nM + β-estradiol 1 nM + curcumin 17 μM and DMSO, for 8 consecutive weeks. Cells were then harvested and counted weekly. After 4 and 8 weeks of treatments, E-cadherin, TGF-β and vimentin expressions were measured using a two-step qRT PCR. At week 8, protein level of TGF-β1 was measured by ELISA, while MCF-7 cell morphology was observed using confocal microscope. Results: MCF-7 cell viability was increased in endoxifen + β-estradiol group. Cell viability was significantly decreased in nanocurcumin and curcumin 17 μM, but not in nanocurcumin 8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNA expressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. The results showed that administration of nanocurcumin in all the dose administered were incapable improving the expressions of vimentin, TGF-β1 and E-cadherin. There were no significant differences between nanocurcumin and curcumin on the modulation of EMT?s markers in breast cancer cells exposed to repeated endoxifen and estradiol. Morphological observation using confocal microscope showed the presence of mesenchymal cells both in the endoxifen+β-estradiol group and the group given nanocurcumin/curcumin. Conclusion: nanocurcumin is incapable to prevent the activation of EMT, although it may reduce cell viability on a long-term use. Although nanocurcumin are more accumulated in the cells, they show no difference in efficacy compared with curcumin in reducing EMT markers.

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Salah satu obat antikanker yang sekarang paling efektif digunakan sebagai kemoterapi kanker ovarium adalah cisplatin. Namun, cisplatin memiliki banyak efek samping pada berbagai organ, salah satunya hepar. Hepatotoksisitas akibat cisplatin menyebabkan terbatasnya dosis kemoterapi cisplatin. Salah satu faktor kunci patofisiologi kerusakan akut hepar adalah inflamasi. Kurkumin merupakan senyawa alami yang memiliki sifat antiinflamasi tetapi bioavailabilitasnya rendah. Untuk itu, diformulasikan nanokurkumin untuk meningkatkan bioavailabilitasnya. Meskipun begitu, efek kurkumin dan nanokurkumin dalam memodulasi jalur inflamasi hepatotoksisitas akibat cisplatin pada kanker ovarium belum diamati. Penelitian ini bertujuan untuk membandingkan pengaruh kurkumin dan nanokurkumin sebagai ko-kemoterapi terhadap hepatotoksisitas cisplatin dalam jalur inflamasi. Penelitian in vivo dilakukan pada tikus Wistar betina yang diinduksi DMBA untuk mendapatkan model kanker ovarium. Kemudian, tikus-tikus diberi perlakuan terapi dengan cisplatin secara intraperitoneal (4 mg/kgBB/minggu) dan kombinasinya dengan kurkumin (100 mg/kgBB/hari) dan nanokurkumin (100 mg/kgBB/hari) per oral. Tikus-tikus tersebut dibagi menjadi kelompok: tikus normal, model kanker ovarium saja, terapi cisplatin, terapi cisplatin + kurkumin, dan terapi cisplatin + nanokurkumin. Setelah 1 bulan, tikus di-sacrifice dan organ hepar disimpan beku. Ekspresi mRNA relatif NF-κB dan IL-1β serta kadar protein IL-6 diukur dengan metode qt RT-PCR dan ELISA secara berurutan. Data hasil pengukuran IL-6 dan data hasil transformasi logaritma NF-κB dan IL-1β dianalisis menggunakan uji one-way ANOVA, menggunakan perangkat lunak SPSS20. Tidak terdapat perbedaan signifikan secara statistik antar kelompok perlakuan dalam mRNA NF-κB (p=0,503), mRNA IL-1β (p=0,237), dan protein IL-6 (p=0,157). Tidak ada perbedaan yang signifikan antara kurkumin dan nanokurkumin dalam memodulasi jalur inflamasi hepatotoksisitas cisplatin pada model kanker ovarium tikus. ...... Up to now, one of the most effective anticancer drug as ovarian cancer chemotherapy is cisplatin. Nevertheless, cisplatin has many side effects on several organs, one of which is liver. Cisplatin-induced hepatotoxicity causes limited cisplatin chemotherapy dose. One of the pathophysiological key factor of acute liver injury is inflamation. Curcumin is natural compound which has antiinflamation properties but the bioavailability is low. To overcome it, nanocurcumin is made to increase its bioavailability. Nonetheless, curcumin and nanocurcumin effect on modulating inflammatory pathway toward cisplatin-induced hepatotoxicity in ovarian cancer rat model has not been observed. This study aims to compare the effect of curcumin and nanocurcumin as co-chemotherapy toward cisplatin-induced hepatotoxicity in inflammatory pathway. An in vivo study was done on female Wistar rats induced by DMBA to achieve ovarian cancer model. Then, rats was treated with cisplatin intraperitoneally (4 mg/kgBW/week) and the combination with per oral curcumin (100 mg/kgBW/day) and nanocurcumin (100 mg/kgBW/day). Those rats were divided into groups, which are normal rat, only ovarian cancer model, cisplatin therapy, cisplatin + curcumin therapy, and cisplatin + nanocurcumin therapy. After 1 month, rats are sacrificed and liver organs are stored frozen. mRNA relative expression of NF-κB and IL-1β as well as protein level of IL-6 was measured using qt RT-PCR and ELISA method, respectively. The result data from the measurement of IL-6 and the data from logarithmic transformation of NF-κB and IL-1β was analysed using one-way ANOVA test using SPSS20 software. There is no significant differences between groups in mRNA NF-κB (p=0.503), mRNA IL-1β (p=0.237), and protein IL-6 (p=0.157). There is no significant differences between curcumin and nanocurcumin in modulating inflammatory pathway of cisplatin-induced hepatotoxicity in ovarian cancer rat model.

Abstrak :
Latar Belakang: Cisplatin adalah obat antineoplastik berbasis platinum yang dipakai untuk berbagai jenis kanker. Walaupun memiliki efikasi yang tinggi, cisplatin memiliki efek samping yang berbahaya, yaitu gagal ginjal akut yang disebabkan oleh stres oksidatif dan inflamasi. Kurkumin diketahui memiliki efek antioksidatif dan antiinflamasi pada gagal ginjal akut yang disebabkan oleh cisplatin, walaupun memiliki bioavailabilitas yang rendah. Hal ini dapat diatasi dengan menggunakan nanokurkumin. Penelitian ini bertujuan untuk membandingkan efektivitas kurkumin dan nanokurkumin dalam melindungi ginjal akibat pemberian dosis tunggal cisplatin, terutama pada ekspresi Nrf2 dan Keap1: Tikus Sprague-dawley jantan (n=25) dikelompokkan menjadi 5 kelompok (Kontrol, cisplatin, cisplatin + curcumin, cisplatin + nanokurkumin 50 mg/kgBB/hari, cisplatin + nanokurkumin 100mg/kgBB/hari, dan dikorbankan 9 hari setelah perlakuan. Sampel ginjal diambil dan dilakukan RT-PCR untuk Nrf2 dan Keap1 Hasil: Pemeriksaan ekspresi gen Nrf2 ditemukan tidak terdapat hubungan yang signifikan antarkelompok (p>0.05). Namun, pada pemeriksaan ekspresi gen Keap1, terlihat ekspresinya lebih tinggi pada tikus yang mendapatkan cisplatin dibandingkan kelompok normal dan ekspresi gen Keap1 juga terlihat lebih tinggi pada kelompok dengan 100mg nanokurkuminKesimpulan Nanokurkumin dapat meningkatkan ekpresi Keap1, walaupun tidak signifikan secara statistik. Hal ini dapat disebabkan oleh karena peningkatan aktivasi Nrf2 yang menyebabkan umpan balik negatif sehingga menurunkan ekspresi Keap1
Background: Cisplatin is a platinum-based drug that is used for various type of cancer. Despite its high efficacy, cisplatin has a very destructive side effect, which is acute kidney failure due to oxidative stress and inflammation. Curcumin has been shown to possess anti-oxidative and anti-inflammatory effect in cisplatin-induced AKI, despite its poor bioavailability, which can be managed by administering nanocurcumin. This study aims to compare the effectivity of curcumin and nanocurcumin in protecting kidney doe to single-dose cisplatin administration, especially in the antioxidative gene Nrf2 and its inhibitor Keap1 Method: Male Sprague-Dawley rat (n=25) are divided into 5 groups (Control, Cisplatin, Cisplatin + Curcumin, Cisplatin + Nanocurcumin 50mg/kgBW, Cisplatin + Nanocurcumin 100mg/kgBW) and sacrificed 9 days after treatment. Kidney sample is taken and RT-PCR for Nrf2 and Keap1 is done.Results: Result of RT-PCR shows no statistical significance in Nrf2 expression across the group (p>0.05). However, Keap1 level was increased in rats treated with 100mg Nanocurcumin. Conculsion: that nanocurcumin can increase Keap1 level but not significantly. This might be caused by increased Nrf2 activation which induce negative feedback thus increasing Keap1 transcription level.

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ABSTRAK
Latar Belakang: Kanker ovarium merupakan salah satu kanker yang menyebabkan kematian paling tinggi pada wanita. Tujuh puluh persen saat didiagnosis ditemukan pada stadium lanjut, dengan angka kesintsan dalam 5 tahun hanya 46 . Modalitas terapi saat ini adalah sitoreduksi dengan kemotterapi adjuvant platinum based sebagai lini pertama. Efektivitas kemoterapi hanya 60 pada stadium lanjut, untuk selanjutnya berkembang menjadi rekuren. Oleh karena itu dibutuhkan jenis terapi tambahan berdasarkan jenis atau agen yang bekerja spesifik di sel kanker dan dapat bersinergi dengan pengobatan standar saat ini. Kurkumin sebagai salah satu agen yang banyak diuji memiliki efek anti-kanker. Kurkumin berpotensi sebagai anti kanker dan bekerja pada semua multistep karsinogenesis. Kurkumin dapat bekerja sebagai antiproliferasi dan meningkatkan apoptosis.Tujuan: untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel hayati SKOV3.Metode: Penelitian ini dilakukan uji eksperimental in vitro dengan menggunakan sel hayati SKOV3 untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel tersebut. Uji analisis data dengan T tidak berpasangan bila sebaran normal / uji Mann Whitney bila sebaran tidak normal serta menggunakan Graph Pad Prism.Hasil: Berdasarkan penelitian ini, didapatkan cc50 nanokurkumin 67 m dan cc50 cisplatin 54 m dengan menggunakan metode MTT Assay. Viabilitas sel pada penelitian ini menurun sesuai dengan dose dependent, dimana pada dosis kombinasi nanokurkumin 134 m dengan cisplatin 108 m ditemukan sel hidup yang paling rendah 24.3 p

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ABSTRACT
Background Ovarian cancer is one of the most leading cancers in women. Seventy percent at the time of diagnosis are found at an advanced stage, with a 5 year survival rate of only 46 . The current treatment modality is cytoreduction with platinum based adjuvant chemotherapy as first line. The effectiveness of chemotherapy is only 60 at an advanced stage, to further develop into recurrent. Therefore, additional types of therapy are required based on types or agents that work specifically in cancer cells and can synergize with current standard treatments. Curcumin as one of the many tested agents has anti cancer effects. Curcumin has the potential effect as an anti cancer and works on all multisteps of carcinogenesis. Curcumin can work as an antiproliferation and increase apoptosis.Objective to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on cell SKOV3.Methods This experimental study was conducted in vitro by using biological cell line SKOV3 to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on the cell. The data was analysed with unpaired T when normal distribution Mann Whitney test when distribution is not normal and also using Graph Pad Prism.Result Based on this result, cc50 of nanokurkumin is 67 m and cc50 of cisplatin is 54 m by using MTT Assay method. The viability of the cells in this study decreased according to the dose dependent, whereas in the combined dose of 134 m nanocurcumin with 108 m cisplatin found the lowest life cell 24.3 p

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ABSTRAK Latar Belakang: Komplikasi diabetes pada jantung dapat terjadi oleh karena produksi reactive oxygen spesies (ROS) berlebih. Beberapa studi menunjukkan stres oksidatif berperan dalam patogenesis komplikasi diabetes seperti kardiomiopati. Kurkumin telah terbukti memiliki khasiat sebagai antioksidan dan kardioprotektif. Tetapi kurkumin memiliki bioavailabilitas yang rendah didalam tubuh. Oleh karena itu kurkumin dibuat dalam bentuk nanokurkumin. Penelitian ini bertujuan untuk mengetahui pengaruh nanokurkumin terhadap stres oksidatif pada jantung tikus yang di induksi diabetes. Metode: Tikus Sprague-Dawley jantan di induksi diabetes dengan nikotinamide (NA) 100 mg/kgBB dan streptozotocin (STZ) 55 mg/kgBB secara intraperitoneal dan dosis tunggal. Terdapat 4 kelompok tikus antara lain, kelompok normal (tikus yang tidak di induksi), kelompok kontrol diabetes (CMC 0,5%), kelompok tikus diabetes yang diberi kurkumin oral 100mg/kg/hari dan kelompok tikus diabetes yang diberi nanokurkumin oral 100mg/kg/hari. Pengamatan dilakukan selama 30 hari. Kadar glukosa darah, aktivitas enzim creatine kinase myocardial band (CKMB), kadar malondialdehid (MDA), aktivitas enzim superoksida dismutase (SOD), glutation peroksidase (GPx) dan histopatologi otot jantung dianalisis dengan statistik menggunakan uji ANOVA, perbedaan dianggap bermakna secara statistik bila p<0.05. Hasil: Pemberian nanokurkumin dan kurkumin tidak mempengaruhi kadar glukosa darah dan cenderung menurunkan aktivitas CKMB pada serum. Nanokurkumin menurunkan kadar MDA jantung. Selain itu, nanokurkumin dan kurkumin dapat meningkatkan aktivitas enzim GPx tetapi tidak mempengaruhi aktivitas enzim SOD. Kurkumin memperbaiki kerusakan otot jantung dan lebih baik dibanding nanokurkumin. Kesimpulan: Hasil penelitian ini menunjukkan bahwa induksi diabetes dan pengamatan selama 30 hari belum memicu kondisi stres oksidatif yang nyata. Nanokurkumin tidak mampu memperbaiki kerusakan otot jantung tetapi mempunyai efek menekan kadar MDA dan meningkatkan aktivitas GPx.

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ABSTRACT Background: Complications of diabetic in the heart may occur due to the excess production of reactive oxygen spesies (ROS). Previous studies showed that oxidative stress played a role in the pathogenesis of diabetic complications such as cardiomyopathy. Curcumin has potential and efficacy as an antioxidant and cardioprotective agent. However, curcumin has low bioavailability in the body. In the present study we investigate the effects of curcumin in the form of nanocurcumin against oxidative stress in the heart from streptozotocinnicotinamide- induced diabetic rats. Methods: Sprague-Dawley rats were induced diabetes with nicotinamide 100mg/kg and streptozotocin55 mg/kg intraperitoneally. Rats were divided into nondiabetic group, diabetic control group (CMC 0,5 %) and two treated groups which were orally given curcumin at a dose of 100 mg/kg/day and nanocurcumin at a dose of 100 mg/kg/day, respectively. After 30 days of observation, the blood glucose levels, activity of the enzyme creatine kinase myocardial band (CKMB), levels of malondialdehyde (MDA), activity of the enzyme superoxide dismutase (SOD), glutathione peroxidase (GPx) and histopathology of the heart muscle were analyzed and the data were assessed using ANOVA test with the level of significancy of p <0.05. Results: Nanocurcumin and curcumin did not decrease blood glucose levels and tended to reduce the activity of CKMB in serum. Nanocurcumin reduced cardiac MDA. Nanocurcumin and curcumin enhanced the activity of GPx enzyme, but did not influence the activity of SOD enzyme. Curcumin appeared to be able to repair injured heart muscle and was better than nanocurcumin. Conclusion: The results of studyindicate that induction of diabetes by streptozotocin-nicotinamide did not result in severe oxidative stress in the rats. Nanocurcumin is not able to repair injured heart muscle but could suppress MDA levels and increase the activity of GPx.

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Latar Belakang: Hiperglikemia kronik pada diabetes akan menyebabkan peningkatan produksi reactive oxygen species ROS yang berkontribusi terhadap progresifitas nefropati. Kurkumin telah terbukti memiliki khasiat renoprotektif pada nefropati diabetik melalui efek antioksidan. Tetapi, kurkumin memiliki kekurangan yaitu, bioavailabilitas rendah, metabolisme lintas pertama yang ekstensif, dan kelarutan yang buruk. Penelitian ini bermaksud untuk mengetahui efek kurkumin dalam bentuk nanopartikel nanokurkumin terhadap tikus diabetes yang diinduksi Streptozotocine-Nikotinamide terhadap progresifitas nefropati melalui hambatan stress oksidatif. Metode: Tikus jantan Sprague Dawley diinduksi diabetes melalui pemberian Nikotinamide 100 mg/kg , dilanjutkan dengan Streptozotocine 55 mg/kg , dosis tunggal, intraperitoneal. Kemudian, tikus dibagi menjadi 4 kelompok; normal, DM tanpa treatment, DM treatment kurkumin 100 mg/kg, dan DM treatment nanokurkumin 100 mg/kg, selama 30 hari. Fungsi fisiologis dinilai berdasarkan BB, GDP, dan rasio berat ginjal. Fungsi ginjal dinilai berdasarkan klirens kreatinin, BUN, dan proteinuria. Kerusakan histologis dinilai dari scoring pewarnaan HE. Stress oksidatif diukur dari kadar malondialdehyde MDA dan kadar superoxide dismutase SOD. Hasil: Meski tidak signifikan, pemberian nanokurkumin menunjukkan efek yang lebih baik daripada pemberian kurkumin berdasarkan parameter SOD, GDP, berat badan, rasio berat ginjal, klirens kreatinin, protein urin, dan gambaran histopatologi. Pemberian nanokurkumin secara signifikan menurunkan kadar BUN. Kesimpulan: Setelah 30 hari pemberian nanokurkumin 100 mg/kg BB maupun kurkumin dengan dosis sama tidak dapat menurunkan stress oksidatif, namun dapat mencegah progresifitas nefropati diabetikum. ...... Background: Chronic hyperglycaemia in diabetes leads to the overproduction of reactive oxygen species ROS that these contribute to the development of diabetic nephropathy. Curcumin, has been recently discovered to have renoprotective effects on diabetic nephropathy DN through its antioxidant properties. However, low peroral bioavailability, extensive first pass metabolism, and low solubility is a major limiting factor for the success of clinical utilization of curcumin. The present study was undertaken to examine the effect of curcumin formed in nanoparticles nanocurcumin treatment in Streptozotocine Nicotinamide induced diabetic rat on the progressivity of nephropathy through its stress oxidative inhibition. Method: Diabetes was induced by Nicotinamide 100 mg kg followed by Streptozotocine 55 mg kg, single dose, intraperitoneal, in male Sprague Dawley rats. Then rats divided into four groups, namely normal, diabetic, diabetic treated with curcumin 100 mg kg, and diabetic treated with nanocurcumin 100 mg kg for 30 days. Physiological function was assessed by body weight, FBG, and kidney weight ratio. Renal function was assessed by creatinine clearance, BUN, and proteinuria. Diabetic renal damage was determined by Hematoxyclin Eosin HE staining. Oxidative stress was measured by renal malonaldehyde MDA level, and superoxide dismutase SOD level. Result: Although did not significant, nanocurcumin showed better effect than curcumin based on SOD, FBG, body weight, kidney weght ratio, creatinine clearance, proteinuria, and renal histopathological changes. Nanocurcumin showed significant decreases in BUN level. Conclusion: After 30 days of treatment, both nanocurcumin and curcumin 100 mg kg did not decreases oxidative stress but showed inhibition in progressivity of nephropathy.

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Latar Belakang: Cisplatin, agen kemoterapi utama dalam terapi kanker ovarium, memiliki sifat hepatotoksik karena menginduksi stres oksidatif. Kurkumin dapat meningkatkan kadar atau aktivitas antioksidan endogen seperti enzim superoksida dismutase dan glutation. Formulasi nanopartikel kurkumin dapat meningkatkan bioavailabilitas kurkumin dan distribusinya pada organ target. Penelitian ini bertujuan untuk mengetahui pengaruh nanokurkumin terhadap hepatotoksisitas akibat cisplatin melalui regulasi antioksidan endogen SOD dan GSH. Metode: 25 ekor tikus galur Wistar betina dibagi ke dalam 1 kelompok sham dan 4 kelompok model kanker ovarium yang diinduksi DMBA pada penelitian in-vivo ini. Empat kelompok tersebut adalah kelompok tanpa terapi, cisplatin 4 mg/KgBB intraperitoneal, cisplatin dengan kurkumin konvensional 100 mg/KgBB per oral, atau cisplatin dengan nanopartikel kurkumin dalam kitosan 100 mg/KgBB per oral. Setelah perlakuan selama 1 bulan, hepar tikus diambil dan disimpan beku. Pengukuran aktivitas SOD, kadar GSH, dan kadar GSSG dilakukan dengan metode spektrofotometri. Hasil: Uji statistik pada kadar GSH, GSSG, dan aktivitas SOD menunjukkan peningkatan yang signifikan pada kelompok ko-kemoterapi kurkumin konvensional dibanding monoterapi cisplatin (p<0.05). Tidak ada perbedaan yang bermakna antarkelompok pada rasio GSH/GSSG (p>0.05) dan tidak ditemukan perbedaan bermakna antara kedua kelompok ko-kemoterapi pada semua variabel (p>0.05). Kesimpulan: Kurkumin konvensional dan nanokurkumin setara dalam meregulasi antioksidan endogen SOD dan GSH pada tikus model kanker ovarium yang mendapat cisplatin. ......Introduction: As the primary chemotherapeutic agent of choice for ovarian cancer, cisplatin has hepatotoxic properties via oxidative stress induction. Curcumin can increase the levels and activities of endogenous antioxidants like superoxide dismutase enzyme and glutathione. Formulation of curcumin nanoparticles increases its bioavailability and target organ distribution. This research aims to elucidate the effects of nanocurcumin on cisplatin-induced hepatotoxicity via regulation of endogenous antioxidants, SOD and GSH. Method: 25 Wistar female rats were grouped into 1 sham group and 4 DMBA-induced ovarian cancer model groups in this in-vivo study. Four cancer model groups were further divided into no-treatment, 100 mg/KgBW intraperitoneal cisplatin therapy, cisplatin with oral 100 mg/KgBW conventional curcumin, and cisplatin with oral 100 mg/KgBW curcumin nanoparticle in chitosan group. The liver of the rats were taken and frozen after one month of treatment. Spectrophotometry was used to measure the activities of SOD, levels of GSH, and levels of GSSG. Results: Statistic tests on levels of GSH, GSSG, and activity of SOD showed significant increase in the curcumin cochemotherapy against cisplatin monotherapy (p<0.05). There was no significant difference within the groups of GSH/GSSG ratio (p>0.05) and no significant difference was found between the curcumin co-chemotherapy and nanocurcumin co-chemotherapy groups in all the variables (p>0.05). Conclusion: Conventional curcumin and nanocurcumin administration are similar in regulating endogenous antioxidants SOD and GSH on rats with ovarian cancer model treated with cisplatin.

Abstrak :

Latar Belakang: Nefrotoksisitas adalah salah satu faktor pembatas utama pengobatan menggunakan cisplatin, dengan basis patofisiologi berupa kematian sel tubulus ginjal pada paparan cisplatin. Efek samping ini cukup umum, yakni terjadi pada satu dari tiga pasien yang menjalani pengobatan dengan cisplatin. Sebuah proses penting yang memperantarai akumulasi cisplatin didalam sel tubulus ginjal adalah transporter-mediated uptake. Dua transporter membran yang telah diketahui terlibat didalam akumulasi aktif cisplatin ke dalam sel tubulus ginjal adalah CTR1 dan OCT2. Kurkumin adalah zat yang dinyatakan memiliki efek renoprotektif.  Studi ini ditujukan untuk mengetahui perbedaan antara efek dari kurkumin dan nanokurkumin dalam mencegah nefrotoksisitas diinduksi cisplatin melalui analisis dari transkripsi level OCT2 pada jaringan ginjal tikus dan untuk menentukan apakah mekanisme renoprotektif dari kurkumin melibatkan CTR1.

Metode: Tikus-tikus jantan Sprague Dawley dibagi menjadi 5 kelompok secara acak: (1) control; (2) cisplatin (7 mg/kg – dosis tunggal, i.p); (3) cisplatin + kurkumin (7 mg/kg – dosis tunggal, i.p + 100 mg/kg/hari); (4) cisplatin + 50 mg nanocurcumin (7 mg/kg – dosis tunggal, i.p + 50 mg/kg/hari); (5) cisplatin + 100 mg nanocurcumin (7 mg/kg – dosis tunggal, i.p + 100 mg/kg/hari). qRT-PCR kemudian dilakukan untuk menghitung ekspresi relatif gen CTR1 dan OCT2 pada ginjal tikus-tikus tersebut.

Hasil: Pemberian 100 mg nanokurkumin meningkatkan ekspresi OCT2 pada tikus yang diberi perlakuan cisplatin, akan tetapi peningkatan tersebut lebih tinggi dibandingkan dengan level ekspresi normal. Sementara itu, ekspresi CTR1 tidak memiliki asosiasi dengan pemberian kurkumin dan nanokurkumin, maka dari itu CTR1 tidak terlibat dalam mekanisme renoprotektif dari kurkumin.

Konklusi: Nanokurkumin memiliki efek renoprotektif yang lebih baik dibandingkan dengan kurkumin sebagaimana didemonstrasikan oleh peningkatan ekspresi OCT2 pada tikus yang mendapat perlakuan cisplatin dan diberikan zat tersebut.

 

 

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Background: Nephrotoxicity is one major limiting factor of cisplatin treatment, with pathophysiological basis of renal tubular cell death upon exposure to cisplatin. This side effect is prevalent, occurring in about one-third of patient undergoing cisplatin treatment.  An important process mediating cellular accumulation of cisplatin inside the renal tubular cell is the transporter-mediated uptake. Two identified membrane transporters involved in the active accumulation of cisplatin into the renal tubular cell are CTR1 and OCT2. Curcumin is a substance which was reported to have renoprotective effects. This study aimed to know the difference between the effects of curcumin and nanocurcumin in preventing cisplatin-induced nephrotoxicity through the analysis of OCT2 transcription level in the rats kidney tissue and to determine whether curcumin renoprotective mechanism involves CTR1.

Method: Male Sprague Dawley Rats were divided into 5 groups in random: (1) control; (2) cisplatin (7 mg/kg – single dose, i.p); (3) cisplatin + curcumin (7 mg/kg – single dose, i.p + 100 mg/kg/day); (4) cisplatin + 50 mg nanocurcumin (7 mg/kg – single dose, i.p + 50 mg/kg/day); (5) cisplatin + 100 mg nanocurcumin (7 mg/kg – single dose, i.p + 100 mg/kg/day). qRT-PCR was then conducted to calculate the relative expression of CTR1 and OCT2 genes in the rats’ kidney.

Results: Administration of 100 mg nanocurcumin increases OCT2 expression in rats treated with cisplatin, but the increase was higher compared to normal expression levels. Whereas CTR1 expression has no association to the administration of curcumin and nanocurcumin, thus is not involved in curcumin’s renoprotective mechanism.

Conclusion: Nanocurcumin has better renoprotective effect compared to curcumin as suggested by the increased OCT2 expression upon its administration in cisplatin-treated rats.