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"Latar Belakang: Kurkumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta- 1,6-diene-3,5-dione) adalah sebuah zat dengan efek renoprotektif. Ketika digunakan dengan cisplatin, kedua zat ini bekerja secara sinergis dengan mengurangi efek nefrotoksik dari cisplatin. Namun, kurkumin memiliki kelarutan yang rendah, metabolism yang cepat, dan farmakokinetik yang buruk. Penggunaan nanopartikel kurkumin (nanokurkumin) dapat meningkatkan ambilan obat sehingga dapat meningkatkan kedayagunaanya dalam situasi klinik. Tujuan peneliatian ini adalah untuk mengevaluasi kadar kurkumin dan nanokurkumin di jaringan ginjal tikus.Metode: Penelitian ini adalah studi eksperimental pada tikus yang diberikan cisplatin dan kurkumin 100 mg/kgbb (Cur100) atau cisplatin dan nanokurkumin 100 mg/kgbb (Nanocur100) atau cisplatin dan nanokurkumin 50mg/kgbb (Nanocur50). Masing-masing kelompok terdiri dari 4 ekor tikus. Kurkumin dan nanokurkumin diberikan selama 7 hari. Sampling dilakukan 24 jam setelah pemberian dosis kurkumin atau nanokurkumin terakhir. Konsentrasi kurkumin dan nanokurkumin dianalisa menggunakan UPLC/MS-MS.Hasil: Data terkumpul disajikan dalam mean ± SEM. Rata-rata konsentrasi dari kurkumin pada grup Cur100 adalah 14.773 (CI: 8.904 – 20.642) pg/mg. Rata-rata konsentrasi dari nanokurkumin pada grup Nanocur100 adalah 11.631 (CI: 0.000 – 25.009) pg/mg. Rata-rata konsentrasi dari nanokurkumin pada grup Nanocur50 adalah 12.548 (CI: 0.563 – 24.534) pg/mg. Hasil dari tes one-way ANOVA adalah 0.805 (p>0.05) sehingga dapat disimpulkan bahwa tidak ditemukan signifikansi pada ketiga kelompok.Kesimpulan: Kurkumin dalam bentuk nanopartikel (nanokurkumin) yang diberikan bersama cisplatin tidak menghasilkan kadar dalam jaringan yang berbeda dibandingkan kurkumin konvensional.

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Background: Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6- diene-3,5-dione) is a substance with renoprotective effect. When used together with cisplatin, it works synergistically by reducing the nephrotoxic effects of cisplatin. However, it has low solubility, rapid metabolism, and poor pharmacokinetics. Usage of curcumin nanoparticle (nanocurcumin) should increase the uptake of the drug thus improving its viability for clinical use. The aim of our study is to evaluate the concentration of curcumin and nanocurcumin in rat kidney tissue.

Methods: This research is an experimental study on rats that were given cisplatin and curcumin 100 mg/kgbw (Cur100) or cisplatin and nanocurcumin 100 mg/kgbw (Nanocur100) or cisplatin and nanocurcumin 50 mg/kgbw (Nanocur50). Each group consists of 4 rats. Curcumin and nanocurcumin were given for 7 days. Sampling were done 24 hours after the last dose of curcumin or nanocurcumin. Concentration of curcumin and nanocurcumin were analyzed using UPLC/MS-MS detection.

Result: Collected data was expressed in mean ± SEM. Mean concentration of curcumin in the first group (Cur100) was 14.773 (CI: 8.904 – 20.642) pg/mg. Mean concentration of nanocurcumin in the second group (Nanocur100) was 11.631 (CI: 0.000 – 25.009) pg/mg. Mean concentration of nanocurcumin in the third group (Nanocur50) was 12.548 (CI: 0.563 – 24.534) pg/mg. The result of one-way ANOVA test was 0.805 (p>0.05) thus concluded that there is no significance difference between the three groups.

Conclusion: Concentration of curcumin in nanoparticle form (nanocurcumin) that were given with cisplatin did not show distinguishable difference in kidney tissue in comparison to conventional curcumin."

"Latar belakang: Mortalitas yang tinggi pada kanker ovarium utamanya disebabkan oleh progresi, kemoresistensi, dan rekurensinya. Diketahui progresivitas dan kemoresistensi kanker ovarium dipengaruhi oleh aksis endothelin, yang melibatkan endothelin-1 dan reseptor endothelin melalui proses epithelial-to-mesenchymal transition (EMT), sehingga menargetkan aksis ini merupakan prospek yang menjanjikan dalam pengembangan agen sensitisasi yang efektif. Kurkumin, senyawa herbal yang banyak di Indonesia, berpotensi menjadi agen ko-kemoterapi kanker ovarium, namun mekanismenya masih belum banyak diketahui. Penelitian sebelumnya menemukan bahwa kurkumin mampu menekan jalur endothelin di beberapa galur sel. Tujuan: Penelitian eksperimental dilakukan untuk menganalisis aktivitas kurkumin sebagai agen ko-kemoterapi cisplatin dalam memodulasi aksis endothelin pada sel SKOV3. Metode: Sampel terbagi menjadi tiga kelompok, yaitu kelompok kontrol (hanya diberikan vehicle), kelompok cisplatin 3,75 μM, serta kelompok kurkumin 5 μM dan cisplatin 3,75 μM. Sel diinkubasi selama 48 jam setelah pemberian perlakuan. Setelah 48 jam, dilakukan pemeriksaan ekspresi mRNA endothelin-1, reseptor endothelin A, dan reseptor endothelin B menggunakan metode qRT-PCR. Hasil: Terdapat penurunan signifikan ekspresi mRNA endothelin-1 pada sel SKOV3 yang diberikan kurkumin bersama cisplatin (0,55±0,32; p=0,005) dibandingkan dengan kelompok kontrol (3,35±2,80). Tidak ditemukan perbedaan dalam ekspresi mRNA reseptor endothelin A dan B yang signifikan antar kelompok. Kesimpulan: Kurkumin sebagai agen ko-kemoterapi cisplatin mampu memodulasi aksis endothelin melalui penekanan ekspresi mRNA endothelin-1, namun tidak melalui penekanan ekspresi mRNA reseptor endothelin A maupun B.

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Background: The high mortality of ovarian cancer is mainly attributed to its progression, chemoresistance to cisplatin, and recurrence. This progression and chemoresistance is mediated by the endothelin axis, which involves endothelin-1 and endothelin receptors through epithelial-to-mesenchymal transition (EMT) process, so targeting this axis is a promising prospect in developing an effective chemosensitizer. According to previous studies, curcumin, a ubiquitous herbal compound in Indonesia, has the potential to be a co-chemotherapeutic agent in ovarian cancer, but its mechanism in cancer progression is still unknown. Previous studies show that curcumin has the ability to modulate endothelin axis in non cancer cells.

Objective: To analyze the activity of curcumin as a co-chemotherapeutic agent with cisplatin in modulating endothelin axis in SKOV3 cells.

Methods: Sample is divided into three groups: control group (only given vehicle), cisplatin 3,75 μM group, and curcumin 5 μM and cisplatin 3,75 μM group. Cells are then incubated for 48 hours. After 48 hours, expression of endothelin-1, endothelin receptor A, and endothelin receptor B mRNAs are measured by qRT-PCR.

Results: There is a significant decrease in endothelin-1 mRNA expression in SKOV3 cells treated with curcumin and cisplatin (0,55±0,32; p=0,005) compared to control group (3,35±2,80). There is no significant difference of endothelin receptor A and B mRNA expression between each group.

Conclusion: Curcumin as a co-chemotherapeutic agent with cisplatin potentially modulates endothelin axis through repression of endothelin-1 mRNA expression, but not endothelin receptor mRNA A or B expression."

"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.

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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."