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Antasena Andra Sidqi
"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.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Ekida Rehan Firmansyah
"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.
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Jakarta: Fakultas Kedokteran Universitas Indonesia , 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Azis Muhammad Putera
"Latar Belakang: Cisplatin, agen kemoterapi pilihan untuk kanker ovarium, bersifat hepatotoksik dengan menginduksi stres oksidatif. Kurkumin adalah agonis jalur Nrf2/Keap1 yang penting dalam respons terhadap stres oksidatif, namun bioavailabilitasnya buruk. Pemberian kurkumin dalam bentuk nanopartikel meningkatkan bioavailabilitasnya dalam tubuh dan distribusinya ke organ target. Penelitian ini bertujuan untuk mengetahui pengaruh nanopartikel kurkumin terhadap hepatotoksisitas cisplatin melalui modulasi jalur Nrf2/Keap1 dilihat dari kadar MDA dan ekspresi gen jalur Nrf2/Keap1.
Metode: 25 ekor tikus Wistar betina dikelompokkan menjadi 5 kelompok yaitu kelompok normal, 4 kelompok model kanker ovarium yang diinduksi DMBA yang dibagi menjadi kelompok tanpa terapi, monoterapi cisplatin 4 mg/KgBB intraperitoneal, ko-kemoterapi cisplatin dan kurkumin konvensional 100 mg/KgBB per oral, serta ko-kemoterapi cisplatin dan nanopartikel kurkumin dalam kitosan 100mg/KgBB per oral selama 1 bulan. Tikus dikorbankan dan hepar disimpan beku. Pengukuran MDA dilakukan dengan metode spektrofotometri, sementara analisis gen jalur Nrf2/Keap1 dilakukan dengan prosedur qRT-PCR.
Hasil: Uji parametrik ANOVA dan post-hoc Tukey menunjukkan adanya penurunan kadar MDA hepar secara bermakna antara kelompok ko-kemoterapi kurkumin konvensional dan ko-kemoterapi nanokurkumin dengan kelompok monoterapi cisplatin (p=0,000 dan p=0,005). Tidak ada perbedaan bermakna antarkelompok pada ekspresi relatif mRNA Keap1 (p=0,190). Tidak ada perbedaan bermakna antara kelompok ko-kemoterapi kurkumin konvensional dengan nanokurkumin terkait ekspresi relatif Nrf2 (p=0,990), HO-1 (p=0,513), dan NQO-1 (p=1,000).
Kesimpulan: Pemberian kurkumin menurunkan kadar MDA jaringan hepar dibanding kelompok monoterapi cisplatin. Tidak ada perbedaan bermakna antara kurkumin konvensional dan nanokurkumin dalam melemahkan hepatotoksisitas cisplatin dilihat dari MDA dan ekspresi gen jalur Nrf2/Keap1.

Introduction: Cisplatin induces hepatotoxicity by oxidative stress-related mechanism. Curcumin activates the Nrf2/Keap1 pathway, modulating cellular response to oxidative stress, but its bioavailability is poor. The administration of curcumin in nanoparticles may increase the bioavailability and distribution of curcumin into tissues. This research aimed to assess the attenuation of cisplatin- induced hepatotoxicity through the modulation of Nrf2/Keap1 pathway by nanocurcumin.
Methods: 25 female Wistar rats were divided into a normal group and four ovarian cancer models by DMBA induction (further classified into a no treatment group, cisplatin monotherapy [4 mg/KgBW i.p.], co-administration of cisplatin and conventional curcumin [100 mg/KgBW p.o.], and co-administration of cisplatin and curcumin-loaded chitosan nanoparticles [100mg/KgBW p.o.]) for a month. The livers of the sacrificed animals were frozen. MDA level was measured by spectrophotometry, while the analysis of Nrf2/Keap1 pathway was done using qRT-PCR.
Results: The ANOVA parametric test showed significant differences between groups in hepatic MDA level ((p<0,001). MDA level was markedly reduced in groups receiving conventional (p<0,001) and nanocurcumin (p=0,005), though there were no significant differences between the administration of conventional and nanocurcumin in MDA level (p=0,277). There were no significant differences between groups in Keap1 relative mRNA expression (p=0,190). No statistically significant differences were observed between groups receiving conventional curcumin and nanocurcumin in the relative gene expression Nrf2 (p=0,990), HO-1 (p=0,513), and NQO-1 (p=1,000) mRNAs.
Conclusion: Curcumin did attenuate cisplatin-induced hepatotoxicity, but no significant differences were observed in hepatic MDA level and relative expression of genes in the Nrf2/Keap1 pathway between conventional curcumin and nanocurcumin administration.
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Depok: Fakultas Kedokteran Universitas Indonesia , 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Ni Nyoman Berlian Aryadevi Meylandari Putri
"Latar Belakang: Selama beberapa dekade, cisplatin menjadi kemoterapi paling aktif yang tersedia untuk kanker ovarium. Terlepas dari keunggulan hasilnya, cisplatin juga memiliki beberapa efek samping, salah satunya adalah hepatotoksisitas. Dalam perkembangan kedokteran, curcumin ditemukan memiliki efek hepatoprotektif dalam beberapa penelitian, tetapi ternyata memiliki bioavailabilitas yang rendah. Dengan demikian, nanocurcumin dibuat dan ditemukan untuk meningkatkan bioavailabilitasnya. Meskipun demikian, efek curcumin dan nanocurcumin dalam hepatotoksisitas yang disebabkan oleh terapi cisplatin pada kanker ovarium belum diamati. Penelitian ini bertujuan untuk menguji pengaruh kedua obat tersebut terhadap hepatotoksisitas yang diinduksi oleh cisplatin. Metode: Percobaan in vivo dilakukan pada tikus Wistar betina, dengan berat 150-200 gram, yang diinduksi oleh DMBA untuk mencapai model kanker ovarium. Kemudian, terapi cisplatin (4mg / kgBB / minggu) diberikan secara intraperitoneal pada tikus. Kemudian beberapa tikus juga diberi terapi kombinasi dengan curcumin (100 mg / kgBB / hari) dan nanocurcumin (100 mg / kgBB / hari). Tikus-tikus ini dibagi menjadi beberapa kelompok: tikus sehat, tidak ada pengobatan, terapi cisplatin, terapi cisplatin + curcumin, dan terapi cisplatin + nanocurcumin. Setelah sebulan, sampel darah diambil dan disentrifugasi untuk mendapatkan plasma. Tingkat AST, ALT, dan ALP diukur menggunakan spektrofotometer untuk menggambarkan fungsi hati. Hasilnya dianalisis menggunakan one-way ANOVA untuk ALT dan ALP dan Kruskall-Wallis untuk AST, menggunakan perangkat lunak SPSS24. Hasil: Tidak ada perbedaan statistik yang signifikan antara kelompok dalam AST plasma (p = 0,125), AlT (p = 0,154), dan ALP (p = 0,072). Kesimpulan: Tidak ada perbedaan yang signifikan untuk kurkumin dan nanokurkumin dalam mengurangi efek hepatotoksisitas cisplatin

Introduction: For decades, cisplatin has remained the most active chemotherapy available for ovarian cancer. Despite the excellence of the outcome, cisplatin also has severe side effects, one of which is hepatotoxicity. In the development of medicine, curcumin was found to exert a hepatoprotective effect in several studies, but it was found to have low bioavailability. Thus, nanocurcumin was established and discovered to improve its bioavailability. Nonetheless, the effect of curcumin and nanocurcumin in hepatotoxicity caused by cisplatin therapy in ovarian cancer has not been observed. This study aims to examine the effect of both drugs on the cisplatin-induced hepatotoxicity. Method: An in vivo experiment was done on female Wistar rats, weighing from 150-200 grams, which was induced by DMBA to achieve ovarian cancer models. Then, cisplatin therapy (4mg/kgBW/week) was given intraperitoneally to the rats. Then some of the rats were also given combination therapy with curcumin (100 mg/kgBW/day) and nanocurcumin (100 mg/kgBW/day). They were divided into groups of: healthy rats, no treatment, cisplatin therapy, cisplatin+curcumin therapy, and cisplatin+nanocurcumin therapy. After a month, blood sample was taken and centrifuged to obtain plasma. The AST, ALT, and ALP level was measured using spectrophotometer to depict the liver function. The result was analysed using one-way ANOVA for ALT and ALP and Kruskall-Wallis for AST using SPSS24 software. Results: Theres no significant statistical difference between groups in plasma AST (p=0.125), AlT (p=0.154), and ALP (p=0.072). Conclusion: There was no significant differences for both curcumin and nanocurcumin in reducing hepatotoxic effect of cisplatin."
Depok: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Skripsi Membership  Universitas Indonesia Library
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Muhammad Farrasy Ammar
"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.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Skripsi Membership  Universitas Indonesia Library
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Erico Wanafri
"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.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2021
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UI - Tesis Membership  Universitas Indonesia Library
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Dimas Kirana Mahaputra
"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
"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.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2017
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UI - Tesis Membership  Universitas Indonesia Library
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Sungkar, Amara Reyzel
"Latar Belakang
Diabetes adalah penyakit metabolik kronis dengan prevalensi global yang meningkat, termasuk di Indonesia. Pada diabetes, peningkatan TNF-α memicu peradangan pada liver, sebagai organ yang berperan dalam metabolisme glukosa dan lemak. Acalypha indica (Ai) adalah tanaman herbal dengan aktivitas antioksidan dan antiinflamasi yang menawarkan alternatif terapi. Penelitian ini bertujuan mengukur kadar TNF-α pada liver tikus diabetes dan menganalisis senyawa dalam akar Ai yang dapat berikatan dengan reseptor target TNF-α menggunakan molecular docking.
Metode
Eksperimen dilakukan pada 25 ekor tikus jantan Sprague-Dawley yang dibagi menjadi lima kelompok, yaitu diet normal, DTFK, DTFK+Pioglitazone, DTFK+Ai 250 mg/kgBB, dan DTFK+Ai 400 mg/kgBB. Setelah 8 minggu, tikus diterminasi dan kadar TNF-α pada organ liver diukur menggunakan ELISA. Molecular docking dilakukan terhadap 58 senyawa ekstrak akar Ai untuk menguji afinitasnya terhadap TNF-α (PDB: 2az5) dengan aplikasi Molegro.
Hasil
Pemberian ekstrak akar Ai dosis 400 mg/kgBB dapat menurunkan kadar TNF-α secara signifikan (P=0,0075) pada organ liver tersimpan dari hewan coba tikus diabetes. Hasil studi molecular docking menunjukkan keseluruhan senyawa memiliki ikatan terhadap TNF-α (PDB: 2az5) dengan afinitas tertinggi dimiliki tanin (skor Moldoc: -231,958; skor Rerank: -109,499), mauritianin (skor Moldoc: -138,252; skor Rerank: -88,8503), 1,2,3,6- Tetragalloyl-beta-D-glucopyranose (skor Moldoc: -136.98; skor Rerank: -75,9225), dan clitorin (skor Moldoc: -122,239; skor Rerank: -93,7471).
Kesimpulan
Pemberian ekstrak akar Ai dapat menurunkan kadar TNF-α di organ liver tikus diabetes yang diperkirakan melalui interaksi utama ligan tanin, mauritanin, 1,2,3,6-tetragalloyl- beta-D-glucopyranose, dan clitorin dalam senyawa Ai.

Introduction
Diabetes is a chronic metabolic disease with a rising global prevalence, including in Indonesia. In diabetes, increased TNF-α triggers liver inflammation, a key organ in glucose and fat metabolism. Acalypha indica (Ai), a herbal plant with antioxidant and anti-inflammatory properties, offers an alternative treatment. This study aims to measure TNF-α levels in diabetic mice liver and analyze Ai root compounds that bind to TNF-α using molecular docking.
Method
Twenty-five male Sprague-Dawley rats were divided into five groups: normal diet, DTFK, DTFK + Pioglitazone, DTFK + Ai 250 mg/kgBW, and DTFK + Ai 400 mg/kgBW. After 8 weeks, rats were terminated and liver TNF-α levels were measured using ELISA. Molecular docking was performed on 58 Ai root extract compounds to test their affinity for TNF-α (PDB: 2az5) with Molegro app.
Results
Administration of Ai root extract at a dose of 400 mg/kgBW can significantly reduce TNF-α levels in the stored liver organs of diabetic rats (P=0,0075). Molecular docking showed all compounds bond to TNF-α (PDB: 2az5) with the highest affinity owned by tannin (Moldoc score: -231.958; Rerank score: -109.499), mauritianin (Moldoc score: - 138.252; Rerank score: -88.8503), 1,2,3,6-Tetragalloyl-beta-D-glucopyranose (Moldoc score: -136.98; Rerank score: -75.9225), and clitorin (Moldoc score: -122.239; Rerank score: -93.7471).
Conclusion
Ai root extract reduces TNF-α levels in the liver of diabetic rats, likely through key interactions with tannin, mauritianin, 1,2,3,6-tetragalloyl-beta-D-glucopyranose, and clitorin found in the Ai compounds.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2024
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UI - Skripsi Membership  Universitas Indonesia Library
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Nanik Sundari
"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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UI - Tesis Membership  Universitas Indonesia Library
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