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Antasena Andra Sidqi
Pengaruh nanokurkumin terhadap hepatotoksisitas cisplatin pada kanker ovarium tikus ditinjau dari TNF-α dan TGF-β1 = Effects of nanocurcumin on cisplatin-induced hepatotoxicity in rat ovarian cancer in terms of TNF-α and TGF-β1
"Latar belakang: Cisplatin merupakan pilihan utama terapi kanker ovarium saat ini, namun memiliki efek samping diantaranya adalah hepatotoksisitas. Salah satu patofisiologi hepatotoksisitas ini adalah melalui jalur inflamasi dan fibrosis. Kurkumin merupakan senyawa yang memiliki efek antiinflamasi dan antifibrosis, namun memiliki bioavailabilitas yang rendah. Pemberian nanopartikel kurkumin diteliti dapat meningkatkan bioavailabilitas kurkumin dalam tubuh.
Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh nanokurkumin pada hepatotoksisitas akibat cisplatin, ditinjau dari kadar TNF-α dan TGF-β1 pada jaringan hati.
Metode: Penelitian in vivo dilakukan pada tikus betina galur Wistar yang dibagi menjadi 5 kelompok perlakuan (1 kelompok normal/sham, dan 4 kelompok diinduksi DMBA untuk mendapatkan model kanker ovarium). Tikus model kanker ovarium diberikan perbedaan perlakuan lagi yaitu satu kelompok tidak diterapi, satu kelompok diterapi cisplatin 4 mg/kgBB secara intraperitoneal, satu kelompok diterapi cisplatin dan kurkumin konvensional 100 mg/kgBB oral, dan satu kelompok diterapi cisplatin dan nanopartikel kurkumin 100 mg/kgBB per oral. Setelah satu bulan pemberian terapi, tikus dikorbankan dan disimpan beku organ hatinya. Pengukuran kadar TNF-α dan TGF-β1 jaringan hati dilakukan dengan metode ELISA.
Hasil: Tidak terdapat perbedaan yang signifikan antar kelompok perlakuan pada kadar TNF-α (p=0.675), dan tidak terdapat perbedaan yang signifikan antara kelompok terapi kurkumin dan nanokurkumin pada kadar TGF-β1 (p=0.992). Simpulan: Pemberian nanokurkumin tidak memengaruhi kadar TNF-α dan TGF-β1 di jaringan hati tikus model kanker ovarium yang mendapat terapi cisplatin.
Introduction: Cisplatin is currently the main choice for ovarian cancer therapy, but it has side effects including hepatotoxicity. One of the pathophysiology of cisplatin-induced hepatotoxicity is through inflammation and fibrosis. Curcumin is a compound that has anti-inflammatory and antifibrosis effects, but has a low bioavailability. The administration of curcumin nanoparticles under study can increase the bioavailability of curcumin in the body. Goals: This study aims to determine the effect of nanocurcumin on cisplatin-induced hepatotoxicity, in terms of levels of TNF-α and TGF-β1 in liver tissue.
Methods: In vivo research was carried out on female Wistar rats divided into 5 treatment groups (1 normal/sham group, and 4 groups induced by DMBA to obtain ovarian cancer models). The ovarian cancer model mice were further classified where one group got no treatment, one group treated with cisplatin 4 mg/kgBW intraperitoneally, one group was treated with cisplatin and conventional curcumin 100 mg/kgBW orally, and one group was treated with cisplatin and curcumin nanoparticles 100 mg/kgBW orally. After one month of therapy, the mice were sacrificed and kept their liver frozen. The measurement of TNF-α and TGF-β1 levels in liver tissue was carried out by the ELISA method.
Results: There was no significant difference between treatment groups in TNF-α levels (p = 0.675), and there was no significant difference between the curcumin and nanocurcumin therapy groups in TGF-β1 levels (p = 0.992).
Concluson: Nanocurcumin therapy did not affect TNF-α and TGF-β1 level in liver tissue in ovarian cancer model mice receiving cisplatin therapy."
Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Ekida Rehan Firmansyah
Modulasi Jalur Inflamasi oleh Ko-kemoterapi Kurkumin dan Nanokurkumin terhadap Hepatotoksisitas Cisplatin pada Model Kanker Ovarium Tikus = Modulation of Inflammatory Pathway by Co-chemotherapy Curcumin and Nanocurcumin toward Cisplatin-induced Hepatotoxicity in Ovarian Cancer Rat Model
"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."
Jakarta: Fakultas Kedokteran Universitas Indonesia , 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Muhammad Farrasy Ammar
Pengaruh Nanokurkumin terhadap kadar antioksidan endogen jaringan hati pada model kanker ovarium yang mendapat cisplatin pada tikus = Effects of Nanocurcumin on hepatic endogenous antioxidants in cisplatin-treated rat ovarian cancer model
"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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Erico Wanafri
Efek nanokurkumin terhadap fungsi ginjal dan inflamasi pada tikus model kanker ovarium yang mendapat cisplatin = The effects of nanocurcumin on kidney function and inflammatory markers in rat model of ovarian cancer treated with cisplatin
"Kemoterapi dengan cisplatin merupakan modalitas utama pada terapi pada kanker ovarium, walaupun telah diketahui toksisitasnya pada berbagai organ termasuk ginjal. Kurkumin, senyawa fenolik yang diperoleh dari Curcuma longa, diketahui memiliki efek proteksi pada ginjal akibat cisplatin pada berbagai model toksisitas in vivo. Namun, efek kurkumin pada ginjal dibatasi oleh bioavailabilitasnya yang rendah. Kelompok penelitian kami telah berhasil mengembangkan formulasi kurkumin nanopartikel baru yang telah terbukti memperbaiki efikasi cisplatin pada model kanker ovarium. Namun, belum diketahui apakah formulasi kurkumin nanopartikel ini juga dapat memperbaiki fungsi dan kondisi inflamasi pada ginjal yang disebabkan oleh cisplatin.
Metode Sebanyak 24 ekor tikus Wistar betina dibagi menjadi: 6 ekor tikus normal (sham treatment) dan 18 ekor tikus yang diinduksi menjadi kanker ovarium dengan DMBA. Tikus kanker ovarium dibagi menjadi 3 kelompok masing-masing 6 ekor yang menerima cisplatin 4 mg/kgBB/minggu atau cisplatin 4 mg/kgBB/minggu +kurkumin 100 mg/kgBB/hari atau cisplatin 4 mg/kgBB/minggu + nanokurkumin 100 mg/kgBB/hari. Terapi diberikan selama 4 minggu, kemudian dilakukan terminasi dan diambil darah dan organ ginjal untuk analisis penanda fungsi ginjal dan inflamasi.
Hasil Nanokurkumin dapat menurunkan kadar ureum serum signifikan dibandingkan kelompok cisplatin, namun tidak mempengaruhi kadar kreatinin dan sedikit menurunkan kadar neutrophil gelatinase-associated lipocalin (NGAL). Nanokurkumin tidak berhasil menurunkan kadar penanda inflamasi: TNF-, IL-1β dan IL-6.
Kesimpulan
Nanokurkumin memiliki kecenderungan untuk memperbaiki beberapa penanda fungsi ginjal dalam darah pada model kanker ovarium yang diberikan cisplatin, namun tidak mempengaruhi kadar penanda inflamasi di ginjal.
The effects of nanocurcumin on kidney function and inflammatory
markers in rat model of ovarian cancer treated with cisplatin
Cisplatin remains the main modality of treatment for ovarian cancer, despite its known toxic effects to various organs, including the kidney. Curcumin, a phenolic compound derived from Curcuma longa, was known to have a renoprotective effect on cisplatin- induced in vivo models. However, the beneficial effect of curcumin on the kidney is limited by its low bioavailability. Our research group has successfully developed a novel curcumin nanoparticle formulation that has been shown to improve the efficacy of cisplatin in ovarian cancer models. However, it is not yet known whether this curcumin nanoparticle formulation can also improve kidney function and inflammatory conditions caused by cisplatin in ovarian cancer models.
Method
A total of 24 female Wistar rats were divided into: 6 normal rats (sham treatment) and 18 rats induced to develop ovarian cancer with DMBA. Ovarian cancer rats were divided into 3 groups of 6 each receiving cisplatin 4 mg/kgBW/week or cisplatin 4 mg/kgBW/week + curcumin 100 mg/kgBW/day or cisplatin 4 mg/kgBW/week + nanocurcumin 100 mg/day. kgBB/day. Therapy was given for 4 weeks, then terminated and blood and kidney were taken for analysis of markers of kidney function and inflammation.
Results
Nanocurcumin lowered serum urea levels significantly compared to the cisplatin group. However, nanocurcumin did not alter creatinine levels and slightly reduced serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations. Nanocurcumin was did not affect the inflammatory markers studied: TNF-, IL-1β and IL-6.
Conclusion
Nanocurcumin has a tendency to improve several markers of kidney function in cisplatin- treated ovarian cancer models. However, the effect was not associated by the alteration of inflammatory cytokines in the kidney."
Depok: Fakultas Kedokteran Universitas Indonesia, 2021
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UI - Tesis Membership  Universitas Indonesia Library
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Dimas Kirana Mahaputra
Efek Nanokurkumin pada Histologi Fibrosis Hati yang Diinduksi 7,12-dimethylbenz(a)anthracene dan Cisplatin sebagai Model Kanker Ovarium pada Tikus = The Effects of Nanocurcumin on Histology of Liver Fibrosis Induced with 7,12-dimethylbenz(a)anthracene and Cisplatin as a Rat Ovarian Cancer Model
"Latar Belakang: Cisplatin sebagai agen kemoterapi merupakan salah satu modalitas terapi pada kanker padat seperti kanker ovarium. Sejumlah studi membuktikan adanya efek samping hepatotoksik cisplatin. Hal ini dapat mengakibatkan kemoterapi tidak efektif, karena dosis cisplatin dikurangi atau bahkan dihentikan pemberiannya. Dewasa ini, obat berbasis tanaman banyak diteliti, salah satunya kurkumin. Kurkumin mempunyai efek hepatoprotektif namun bioavailabilitasnya sangat rendah. Sejumlah penelitian membuat formula nanokurkumin untuk meningkatkan bioavaibilitasnya. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian nanokurkumin pada gambaran histologis jejas liver yang diinduksi oleh cisplatin pada tikus model kanker ovarium. Metode: Penelitian ini menggunakan bahan biologis tersimpan dari penelitian sebelumnya. Terdapat 5 kelompok perlakuan; kontrol, DMBA; DMBA+Cisplatin; DMBA+Cis+kurkumin; dan DMBA+Cis+nanokurkumin. Pewarnaan Masson Trichrome dipakai untuk mengamati akumulasi kolagen sebagai penanda fibrosis. Selanjutnya dilakukan kuantifikasi jaringan kolagen /Collagen Proportionate Area (CPA), serta skoring fibrosis hati (skor ISHAK). Hasil: Induksi DMBA dan terapi cisplatin dapat mengakibatkan fibrosis hati, ditandai dengan deposisi kolagen yang lebih tinggi dibanding kelompok kontrol. Pemberian nanokurkumin menunjukkan adanya perbaikan secara histologis berupa fibrosis periportal yang ringan dan skor fibrosis yang lebih rendah secara signifikan (p<0.05) dibanding kelompok lainnya. Pemberian nanokurkumin juga menunjukkan persentase akumulasi kolagen (CPA) yang rendah, namun tidak signifikan (p>0.05) secara statistik. Kesimpulan: Pemberian nanokurkumin pada model kanker ovarium yang diterapi dengan cisplatin pada tikus menunjukkan efek hepatoprotektor dengan memperbaiki skor fibrosis dan mengurangi akumulasi kolagen pada jaringan liver. Diperlukan penelitian lebih lanjut yang membandingkan beragam dosis dan formulasi untuk mengetahui efikasi nanokurkumin yang paling baik sebagai hepatoprotektor pada model kanker ovarium yang diterapi dengan cisplatin.
Background: Cisplatin as a chemotherapy is one of the main modalities of therapy in patients with solid tumours like ovarian cancer. Studies have proven the hepatotoxicity of cisplatin, which causes dose reduction and even termination. Nowadays, herbal based drug is intensively studied, one of them is curcumin. Curcumin is known to have a hepatoprotective effect, albeit with very low bioavailability. To solve this, many research have formulated nanocurcumin to increase its bioavailability. This research aims to find out the effect of nanocurcumin in liver fibrosis induced by cisplatin in ovarian cancer of rat’s model. Method: Our study uses stored biological materials from previous study. The groups are; Control; DMBA; DMBA+Cisplatin; DMBA+Cisplatin+Curcumin; DMBA+Cisplatin+Nanocurcumin. Liver fibrosis is observed with Masson Trichrome stain to view collagen accumulation as fibrosis marker. Afterwards, quantification of collagen fibers (CPA) and liver fibrosis grading (ISHAK) is done. Results: Induction of DMBA with cisplatin treatment causes liver fibrosis, indicated by higher collagen deposition compared to the normal group. Administration of nanocurcumin shows improvement in histological structure such as milder periportal fibrosis and significantly lower liver fibrosis grade (p<0.05) compared to other groups. Administration of nanocurcumin also results in lower collagen percentage (CPA), however it is statistically insignificant (p>0.05). Conclusion: Administration of nanocurcumin in rat ovarian cancer model treated with cisplatin shows hepatoprotective effect by reducing both fibrosis grade and collagen accumulation in the liver. Further study is required with varying dose and formulations to know the nanocurcumin’s best efficacy as hepatoprotector in ovarian cancer model treated with cisplatin.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Skripsi Membership  Universitas Indonesia Library
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Shinta Dewi Permata Sari
Efek pemberian kurkumin dan nanokurkumin pada tikus dengan nefrotoksisitas yang diinduksi cisplatin melalui jalur ERKe1/2 = The effects of nanocurcumin and curcumin on cisplatin induced nephrotoxicity through ERK1/2 pathway in rat
"Nefrotoksisitas merupakan efek samping utama yang membatasi penggunaan cisplatin sebagai obat anti-tumor. Kurkumin memeliki beberapa aktivitas farmakologis salah satunya, yaitu sebagai nefroprotektor. Akan tetapi kurkumin kurang larut di dalam air, sehingga digunakan nanokurkumin yang lebih mudah larut/terdispersi dalam air. Tujuan penelitian ini adalah untuk mengetahui efek kurkumin dan nanokurkumin terhadap nefrotoksisitas tikus yang diinduksi cisplatin melalui jalur ERK1/2. Perlakuan hewan coba dilakukan selama 10 hari, menggunakan tikus Sprague Dawley yang dibagi menjadi 5 kelompok, n=6, yaitu kelompok normal, cisplatin CIS, Cisplatin kurkumin 100 mg/kgBB/hari p.o Cis Kurku100, Cisplatin nanokurkumin 50 mg/kgBB/hari p.o Cis Nanokur50, Cisplatin nanokurkumin 100 mg/kgBB/hari p.o Cis Nanokur100 . Pada hari ke-7 dilakukan injeksi cisplatin 7 mg/kgBB, i.p dan 72 jam setelah injeksi cisplatin dilakukan pengambilan darah dan organ ginjal. Cisplatin dosis tunggal pada kelompok CIS menyebabkan peningkatan kadar BUN dan kreatinin dalam plasma, kadar MDA, peningkatan rasio ekspresi BCL-2/Bax, serta peningkatan rasio ekspresi protein p-ERK/ERK secara signifikan, dibandingkan kelompok normal. Pemberian kurkumin 100 mg/kgBB dan nanokurkumin 100 mg/kgBB berperan sebagai antioksidan untuk mencegah progresifitas nefrotoksisitas akibat cisplatin, dilihat melalui terjadinya penurunan kadar BUN dan kreatinin dalam plasma, penurunan kadar MDA, dan peningkatan rasio ekspresi gen BCL-2/Bax secara signifikan dibandingkan kelompok CIS, serta penurunan rasio ekspresi protein p-ERK/ERK secara signifikan dibandingkan kelompok CIS. Cisplatin dosis tunggal 7 mg/kgBB dapat menyebabkan nefrotoksisitas pada tikus yang menyerupai AKI Acute Kidney Injury pada manusia. Kurkumin 100 mg/kgBB cenderung memiliki efek nefroprotektor yang lebih baik dalam mencegah progresifitas nefrotoksisitas akibat cisplatin melalui jalur stress oksidatif dan apoptosis.
Nephrotoxicity is the major limitation for the clinical use of cisplatin as an antitumor. Curcumin has some pharmacological activity, one of them as nephroprotector. However, curcumin less soluble in water, so it is used nanocurcumin which is readily dispersed in aqueous media. The purpose of this study is to investigate the effects of curcumin and nanocurcumin against ciplatin induced nephrotoxicity in rats through ERK1 2 pathway. This study conducted for 10 days treatment, five groups n 6 of male Sprague Dawley rats were examined normal, cisplatin CIS 7 mg kgBW, Cis curcumin Cis Curcu100 100 mg kg BW day, Cisplatin nanocurcumin 50 mg kg BW day Cis Nanocur50, and Cisplatin nanocurcumin 100mg kg BW day Cis Nanocur100 . After 72 h following injection cisplatin, specimens were collected. This study resulted a single dose of cisplatin in CIS group caused a significant increased in plasma BUN, plasma creatinine, MDA levels, decreased ratio expression of BCL 2 Bax gene, and increased ratio of p ERK ERK as compared to normal group. Pre treatment with curcumin 100 mg kgBW and nanocurcumin 50 and 100 mg kgBW acts as an antioxidant to prevent progression of nephrotoxicity cisplatin, were reduced plasma BUN levels, plasma creatinine levels, MDA levels in kidney, increased GSH level in kidney, increased ratio expression of BCL 2 Bax gene in kidney, and decreased ratio of p ERK ERK protein in kidney compared with cisplatin induced nephrotoxicity rats without treatment. Cisplatin with single dose 7 mg kgBW is able to induced nephrotoxicity in rats that mimicked acute kidney injury in human. Curcumin 100 mg kgBW tend to have a better nephroprotector effect in preventing the progression of cisplatin induced nephrotoxicity through oxidative stress pathways and apoptosis. "
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2017
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UI - Tesis Membership  Universitas Indonesia Library
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Nanik Sundari
Kajian aktivitas antioksidan, modulasi sitokin TNF-α dan TGF-β1 oleh mahkota dewa (Phaleria macrocarpa) pada pencegahan fibrosis hati pada tikus yang diinduksi karbon tetraklorida = Antioxidant, TNF- α and TGF-β1 modulating properties of Mahkota dewa (Phaleria macrocarpa) on the prevention of carbon-tetrachloride induced liver fibrosis in rats
"Latar belakang: Mahkota dewa (Phaleria macrocarpa) merupakan salah satu tanaman herbal di Indonesia dan ekstrak air buah mahkota dewa telah terbukti memiliki efek hepatoprotektif. Penelitian ini bertujuan untuk mengetahui aktivitas dan mekanisme kerja ekstrak air buah mahkota dewa dalam mencegah terjadinya fibrosis hati.
Metode: Penelitian dilakukan pada tikus Sprague-Dawley jantan yang diinduksi karbon tetraklorida (CCl4) secara intraperitoneal setiap 3 hari sekali selama 8 minggu. Hewan coba dibagi menjadi 6 kelompok: normal, CCl4, n-Acetyl cysteine (NAC) dosis 150 mg/kgBB, ekstrak air buah mahkota dewa dosis 50, 100 dan 150 mg/kgBB. Penilaian dilakukan terhadap parameter aspartat aminotransferase (AST), alanin aminotransferase (ALT), alkali fosfatase (ALP), histopatologi hati, kadar malondialdehid (MDA), rasio GSH/GSSG, kadar Tumor Necrosis Factor (TNF)-α dan kadar Transforming Growth Factor (TGF)-β1
Hasil: Hasil studi menunjukkan bahwa ekstrak air buah mahkota dewa dan NAC secara bermakna dapat melindungi hati dari cedera melalui penurunan aktivitas enzim ALT, AST, ALP dan penurunan persentase jaringan ikat pada pemeriksaan histopatologi. Ekstrak air buah mahkota dewa dan NAC dapat menghambat stress oksidatif melalui penurunan kadar MDA hati dan peningkatan rasio GSH/GSSG hati. Ekstrak air buah mahkota dewa dan NAC dapat menekan inflamasi melalui penurunan kadar TNF-α dan menghambat aktivasi sel stelata hati (HSC) yang ditandai dengan penurunan kadar TGF-β1.
Kesimpulan: Ekstrak air buah mahkota dewa dapat mencegah fibrosis hati pada tikus yang diinduksi CCl4. Pencegahan terhadap fibrosis tersebut terutama melalui aktivitas antioksidan dan kemampuan menekan sitokin inflamasi TNF-α, serta menghambat aktivasi HSC melalui penurunan sitokin fibrogenik TGF-β1.
Introduction: Mahkota dewa (Phaleria macrocarpa) is one of the Indonesian herbal plants. Hepatoprotective effect of aqueous extract of mahkota dewa fruits have been studied previously. This study was conducted to evaluate the activity of water extract of mahkota dewa in the prevention of liver fibrosis and its mechanism of action.
Method: Male Sprague-Dawley rats were induced by carbon tertrachloride (CCl4) given every 3 days by intraperitoneal injection for 8 weeks. Rats were randomly allocated into 6 groups: control group, n-acetyl cysteine/NAC (150 mg/kgBB), aqueous extract of mahkota dewa (50, 100 and 150 mg/kgBB). Aspartate aminotransaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), liver histopathology, malondialdehyde (MDA), ratio GSH/GSSG, Tumor Necrosis Factor (TNF)-α and Transforming Growth Factor (TGF)-β1 were examined.
Results: This study demonstrates that aqueous extract of mahkota dewa and NAC significantly protects the liver from injury by reducing the activity of AST, ALT, ALP and by reducing fibrosis percentage in histopatological examination. Aqueous extract of mahkota dewa and NAC attenuates oxidative stress by reducing the levels of MDA and increasing GSH/GSSG ratio. Aqueous extract of mahkota dewa and NAC suppresses inflammation by reducing the levels of TNF- α and inhibits hepatic stellate cells (HSC) activation by reducing the levels of TGF-β1.
Conclusions: Aqueous extract of mahkota dewa prevents CCl4-induced fibrosis in rats. The prevention of liver fibrosis most possibly through its antioxidant activities, suppression of inflammatory cytokines TNF-α and inhibition of HSC activation by reducing fibrogenic cytokines TGF-β1."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
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Muhammad Yusuf
Efek antiproliferasi dan apoptosis kombinasi cisplatin dan nanokurkumin pada kultur sel hayati kanker ovarium skov3 = Effects of antiproliferation and apoptosis combination of cisplatin and nanocurcumin in culture of ovarian cancer cells skov3 / Muhammad Yusuf
"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
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 "
2018
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Sri Yunita
Efek Pemberian Ekstrak Hibiscus sabdariffa Linn terhadap Inflamasi Jantung Tikus pada Kondisi Overtraining: Kajian IL-6, ERK5, dan TNF-α = The Effect of Hibiscus sabdariffa Linn on Inflammatory Condition: Study of IL-6, ERK5, and TNF-α
"Latihan fisik bermanfaat menjaga kesehatan dan meningkatkan performa atlet. Ketika menghadapi kompetisi, atlet kadang meningkatkan beban latihan tanpa istirahat cukup sehingga terjadi overtraining syndrome (OTS). Pada OTS ditemukan berbagai gejala adaptasi patologis berbagai sistem organ tubuh, termasuk di jantung. Selain itu, terjadi peningkatan kadar IL-6 dan TNF-α sistemik. IL-6 akan berikatan dengan reseptornya dan mengaktivasi IL-6/MEK5/ERK5 sehingga terjadi hipertrofi jantung. Hibiscus sabdariffa Linn (HSL) diketahui memilki efek anti inflamasi.
Penelitian ini ingin mengetahui pengaruh overtraining dan pemberian HSL pada overtraining terhadap status inflamasi jantung. Penelitian menggunakan jaringan jantung dari 25 ekor tikus Wistar berusia 8-10 minggu, berat badan 300-350 gram. Tikus dibagi menjadi 5 kelompok, yaitu kontrol (C), kontrol + Hibiscus (C+HSL), aerobik (A), Overtraining, dan Overtraining + HSL. Perlakuan dilakukan selama 11 minggu. Pada akhir penelitian, dilakukan pengukuran kadar IL-6, ERK5, dan TNF-α.
Hasil penelitian menunjukkan kadar IL-6 dan ERK5 tidak berbeda bermakna antar kelompok. Kadar TNF-α pada kelompok latihan fisik overtraining (206,7±40,96 pg/mg), lebih tinggi secara bermakna jika dibandingkan dengan kontrol (93,03±20,23 pg/mg). Pada kelompok overtraining + HSL, kadar IL-6 (17,62±14,42 pg/mg) dan TNF-α (44,95±6,252 pg/mg) lebih rendah secara bermakna bila dibandingkan kelompok overtraining. Dari penelitian ini disimpulkan bahwa overtraining menyebabkan inflamasi di jantung dan pemberian HSL dapat menguranginya.
Physical exercise is beneficial for maintaining health and increasing the performance of athletes. When facing a competition, athletes sometimes increase their training load without adequate rest so overtraining syndrome (OTS) occured. Various symptoms of pathological adaptation in various body organ systems are found in OTS, including in the heart. In addition, there was an increase in IL-6 and systemic TNF-α levels. IL-6 will bind to its receptors and activate IL-6/MEK5/ERK5 resulting in cardiac hypertrophy. Hibiscus sabdariffa Linn (HSL) is known to have anti-inflammatory effects.
This study wanted to find out the effect of overtraining and administration of HSL in overtraining on the inflammatory status of the heart. The study used heart tissue from 25 Wistar rats aged 8-10 weeks, weighing 300-350 grams. Rats were divided into 5 groups, namely control (C), control + Hibiscus (C + HSL), aerobics (A), Overtraining, and Overtraining + HSL. The treatment was carried out for 11 weeks. At the end of the study, IL-6, ERK5, and TNF-α level were measured.
The results showed that level of IL-6 and ERK5 did not differ significantly between groups. TNF-α level in the overtraining exercise group (206.7 ± 40.96 pg/mg) were significantly higher when compared to the controls (93.03 ± 20.23 pg/mg). In the overtraining + HSL group, IL-6 levels (17.62 ± 14.42 pg / mg) and TNF-α (44.95 ± 6.252 pg/mg) were significantly lower than the overtraining group. It was concluded from this study that overtraining causes inflammation in the heart and administration of HSL can reduce it."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
T59127
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Dian Elco Nora
Efek Ekstrak Etanol Temu Mangga (Curcuma Mangga Val.) Terhadap Penurunan Kadar TNF-α Dan Gambaran Histopatologi Pada Kolon Mencit Yang Diinduksi DSS = The Effects Of Ethanol Extracts Temu Mangga (Curcuma Mangga Val.) To Decrease In TNF-α Levels, And Colonic Histopathology Picture Mice Induced By DSS
"Secara global dikatakan bahwa insidens Inflammatory bowel disease (IBD) adalah 10 kasus per 100.000 penduduk. Fokus utama rencana Terapeutik IBD adalah upaya penghambatan kaskade proses inflamasi. Temu mangga (Curcuma mangga val) diketahui memiliki efek anti inflamasi. Dalam penelitian ini ingin diketahui efektivitas ekstrak Temu mangga (Curcuma mangga Val) dalam menurunkan kadar TNF-α dari serum mencit dan perbaikan gambaran histopatologi kolon model mencit Inflammatory bowel disease (IBD). Pengukuran TNF-α dengan metode Elisa dan gambaran histopatologi kolon dengan pewarnaan HE. Pada penelitian ini mencit diinduksi menggunakan DSS 2% yang dicampurkan dengan air minum dan diinduksi selama 9 hari dilanjutkan dengan pemberian ekstrak etanol Temu mangga selama 14 hari. Pada penelitian ini ada 6 kelompok hewan perlakuan yaitu K0 (baseline), DS,  PD, MD4, MD8, MD16. Perhitungan statistik menggunakan uji parametrik ANOVA untuk penurunan TNF-α, dan jumlah sel goblet. Skoring perubahan jaringan kolon (metode cooper). Hasil perhitungan menunjukkan penurunan kadar TNF-αterutama pada kelompok  MD16. Dimana penurunan TNF-α pada MD16 berbeda bermakna (p<0,05) dengan DS. Skor perubahan  jaringan kolon (metode cooper) MD16 memperlihatkan hasil berbeda bermakna (p<0,05) dengan DS. Efek Perlakuan dengan dosis Temu mangga 16 mg/20 gram mencit memberikan hasil yang lebih baik pada regenerasi sel dibanding dosis 8 mg/20 gram mencit dan 4 mg/20 gram mencit. Hal ini ditunjukkan dari gambaran Histopatologi kolon yang ditandai peningkatan jumlah sel goblet dan penurunan jumlah lokasi radang .
Globally it is said that the incidence of Inflammatory bowel disease. (IBD) is 10 cases per 100,000 population. The main focus of the plan is an attempt IBD Therapeutic inhibition of the inflammatory cascade process. Temu mangga ( Curcuma mangga val) is known to have anti-inflammatory effects. In this study we want to know effectiveness Temu mangga extract (Curcuma mangga Val) in lowering levels of serum TNF-α mice and improvement of colonic histopathology picture mice model of Inflammatory bowel disease (IBD). Measurement of TNF-α with Elisa method and description of colonic histopathology with HE staining. In this study, mice were induced using DSS 2% that is mixed with water and induced for 9 days followed by ethanol extract of Temu mangga appointment for 14 days. In this study, there are six groups of animals ie K0 treatment (baseline), DS, PD, MD4, MD8, MD16. Statistical calculations using ANOVA parametric test for the decline in TNF-α, and the number of goblet cells. Scoring changes in colonic tissue (method cooper). The calculations show decreased levels of TNF-α, especially in group MD16. Where the reduction in TNF-α in MD16 significantly different (p<0,05) with DS. Score changes in colonic tissue (method cooper) MD16 showed significantly different results (p<0,05) with DS. The treatment effects at a dose of 16 mg Temu mangga/20 gram mice provide better results in the regeneration of the cells compared to the dose of 8 mg/20 gram mice and 4 mg/20 gram mice. It is shown on the picture Histopathology of colonic marked increase in the number of goblet cells and decrease the number of locations inflammation."
Depok: Fakultas Farmasi Universitas Indonesia, 2017
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