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"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

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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."

"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.

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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. "

"Latar Belakang : alfa mangostin merupakan kandidat yang bisa menyembuhkan penyakit hati yang disebabkan oleh alkohol. Kerusakan yang disebabkan oleh alkohol, akan dikompenasasi hati dengan mensekret matrix extracellular (ECM). Matrix metalloproteinase (MMP) memiliki peran untuk mendegredasi matrix extraceluler. Tujuan dari studi ini adalah menginvestigasi expresi mRNA MMP2 dan MMP9 pada model alcoholic liver disease in-vitro. Metode : Penilitian ini merupakan experimen in-vitro, dengan galur sel stelata hepatic LX-2. Terdapat 6 kelompok perlakuan yaitu: tanpa obat, asetaldehid, acetaldehid + sorafenib 10μM, asetaldehid + 10μM alpha mangsotin, asetaldehid + 20 μM, dan alfa mangosteen 10μM. Lalu, sample diproses dan dianalisis expresi gen MMP2 dan MMP9 menggunakan qRT-PCR. Hasil : Acetaldehide meningkatkan expresi mRNA MMP2 dan MMP9 secara signifikan. Alfa-mangostin menurunkan ekspresi mRNA MMP2 dan MMP9 pada sel stelata hepatic yg diberikan asetildehid. Sedangkan sel yang diberi alpha mangosteen tidak mempengaruhi expresi MMP2 namun menurunkan expresi MMP9. Konklusi : Alfa mangosteen menurunkan expresi mRNA dari MMP2 dan MMP9. Pada sel stelata hepatic yang diinduksi asetildehid.

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Background : Alpha mangosteen is a possible candidate to treat liver disease that is caused by alcohol. The liver compensate for damage done by alcohol through secreting extracellular matrix (ECM). Matrix metalloproteinase (MMP) has a role in degrading extracellular matrix. Thus, the purpose of study is to investigate MMP2 and MMP9 mRNA expression on an alcoholic liver disease model done in in-vitro.

Method : Study using In-vitro method using LX-2 Hepatic Stelate cells strain. There are 6 groups of sample and each one of the samples were treated: Without drugs, acetyldehyde, acetyldehyde + 10μM sorafenib, acetyldehyde + 10μM alpha mangosteen, acetyldehyde + 20μM alpha mangosteen, amd alfa mangosteen 10μM. And then, the expression of genes is analyze using qRT-PCR.

Results : Acetaldehyde increased MMP2 and MMP9 mRNA expression significantly. Alpha-mangosteen decrease MMP2 and MMP9 mRNA experssion in hepatic stellate cells induced by acetyldehyde. Meanwhile, cells that were given alpha mangosteen did not affect mRNA expression of MMP2 although decrease MMP9 expression.

Conclusion : Alpha mangosteen decrease mRNA expression of MMP2 and MMP9, in hepatic stelate cells induced by acetyldehyde."

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Latar Belakang: Cisplatin telah menjadi terapi lini pertama untuk kanker ovarium, namun efek samping terbesar cisplatin adalah peningkatan resistensi sel kanker yang menyebabkan hepatotoksisitas pada sel normal. Kurkumin terbukti memiliki sifat hepatoprotektif, tetapi efek terapeutik kurkumin terbatas karena memiliki bioavailabilitas yang rendah. Penggunaan kitosan nanopartikel pada kurkumin telah terbukti meningkatkan bioavailabilitas kurkumin sehingga efektivitasnya lebih besar. Penelitian ini dilaksanakan untuk melihat pengaruh nanokurkumin terhadap hepatotoksisitas akibat pemberian cisplatin. Tujuan: Membandingkan pengaruh kurkumin dan nanopartikel kurkumin untuk digunakan sebagai ko-kemoterapi dengan cisplatin pada kanker ovarium tikus yang ditinjau melalui jalur apoptosis, khususnya marker Bax dan Kaspase-3. Metode: Penelitian ini merupakan penelitian eksperimental in vivo pada model kanker ovarium tikus betina galur Wistar yang diinduksi 7,12-dimethybenzen[a]anthracene (DMBA) dan dilaksanakan di Departemen Farmakologi dan Terapeutik Fakultas Kedokteran Universitas Indonesia sejak bulan Juni 2019 hingga Juni 2020. Cisplatin diberikan dalam dosis sebesar 4 mg/kgBB secara intraperitoneal. Kurkumin dan nanokurkumin diberikan dalam dosis oral sebesar 100 mg/kgBB. Organ tersimpan hepar yang diambil dari 25 ekor tikus terbagi menjadi 5 kelompok perlakuan, yaitu kelompok tikus normal, model kanker ovarium tikus, terapi cisplatin, terapi cisplatin + kurkumin, dan terapi cisplatin + nanokurkumin. Setelah dikelompokkan, dilakukan homogenisasi sampel yang terpilih. Lalu, RNA Bax dan Kaspase-3 diisolasi dari homogenat sampel organ hepar dan cDNA kedua gen disintesis. Kemudian, tingkat ekspresi mRNA Bax dan Kaspase-3 pada hepar diukur menggunakan qRT-PCR. Data ekspresi mRNA Bax dan Kaspase-3 dianalisis dan diuji korelasi antarkelompok menggunakan aplikasi SPSS. Hasil: Tidak ada perbedaan yang signifikan antara kelima kelompok pada tingkat ekspresi mRNA Bax (p=0,372) dan Kaspase-3 (p=0,111). Kesimpulan: Tidak ditemukan pengaruh kurkumin dan nanokurkumin terhadap ekspresi mRNA Bax dan Kaspase-3 organ hepar pada model kanker ovarium tikus setelah pemberian terapi cisplatin.

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Background: Cisplatin has become the first-line therapy for ovarian cancer, but it has a side effect of increasing cancer cell resistance which causes hepatotoxicity in normal cells. Curcumin has been shown to have hepatoprotective properties, but its therapeutic effect is limited because of its low bioavailability. The use of chitosan nanoparticles in curcumin has been shown to increase the bioavailability of curcumin. This research was conducted to see the effect of nanocurcumin on hepatotoxicity due to cisplatin administration. Aim: Comparing the effect of curcumin and curcumin nanoparticles as co-chemotherapy with cisplatin in rat ovarian cancer that is evaluated through apoptotic pathways, specifically Bax and Kaspase-3 markers. Methods: This research is an in vivo experimental study on a female ovarian cancer model of Wistar rats induced 7,12-dimethybenzen[a]anthracene (DMBA) and was carried out in the Department of Pharmacology and Therapeutics of the Faculty of Medicine, University of Indonesia from June 2019 to June 2020. Cisplatin is given in doses of 4 mg/kgBW intraperitoneal. Curcumin and nanocurcumin are given in oral doses of 100 mg/kgBW. Stored liver organs which was taken from 25 rats was divided into 5 treatment groups which are normal, ovarian cancer model, cisplatin therapy, cisplatin + curcumin therapy, and cisplatin + nanocurcumin therapy group. After the samples are grouped, homogenization of the selected sample is carried out. Then, the Bax and Kaspase-3 RNA were isolated from the homogenate samples and the cDNA of the two genes was synthesized. Then, the levels of Bax and Kaspase-3 mRNA expressions in the liver were measured using qRT-PCR. Bax and Kaspase-3 mRNA expressions were analyzed and tested intergroup correlations using the SPSS application. Results: There were no significant differences between the five groups in the expression levels of Bax mRNA (p=0,372) and Kaspase-3 (p=0,111). Conclusion: This study shows no effect of curcumin and nanocurcumin on the expression of Bax and Caspase-3 liver organ mRNA in rat ovarian cancer models after cisplatin therapy.

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"Leukemia granulositik kronik (LGK) merupakan salah satu penyakit keganasan hematologi yang prevalensinya dapatterus meningkat di masa depan. Terapi LGK saat ini adalah imatinib yang merupakan tirosin kinase inhibitor. Meskipun imatinib memiliki kemampuan klinis superior, diperkirakan sekitar 20-30% pasien LGK resisten terhadap terapi imatinib,yang salah satu penyebabnya terkait ekspresi P-gp berlebih, sehingga memompakan imatinib intraseluler ke domain ekstraseluler. P-gp disandi oleh gen ABCB1 yang bersifat sangat polimorfik, tiga single nucleotide polymorphism (SNP) telah diteliti pada pasien LGK, yaitu C1236T, C3435T dan G2677T/A. Mutasi yang paling umum terjadi untuk memprediksi respons klinis terapi imatinib pada pasien LGK Asia adalah mutasi C1236T. Penelitian ini bertujuan untuk mengetahui hubungan mutasi C1236T gen ABCB1 dengan pencapaian MMR pada pasien LGK fase kronik yang mendapat imatinib.Metode: Penelitian ini merupakan penelitian potong lintang (cross-sectional) menggunakan 120 sampel darah pada pasien LGK fase kronik yang mendapat imatinib mesilat selama ≥ 12 bulan yang memenuhi kriteria seleksi. Dilakukan amplifikasi dengan metode PCR dilanjutkan dengan sekuensing metode Sanger untuk penentuan mutasi C1236T gen ABCB1.Hasil: Dari 120 sampel darah yang memenuhi kriteria seleksi dan dianalisis. Terdapat 28,3% pasien LGK fase kronik yang mencapai MMR. Mutasi C1236T adalah 72 pasien (60%). Tidak terdapat hubungan mutasi dengan pencapaian MMR (risiko prevalensi 0,717 [0,275-1,461], p = 0,282).Kesimpulan: Tidak terdapat hubungan antara mutasi C1236T gen ABCB1 pada pasien LGK fase kronik yang mendapat imatinib 12 bulan dengan pencapaian MMR.

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Chronic myeloid leukemia (CML) is one of the hematological malignancy disease which prevalence may continue to increase in the future. The treatment option of CML recently is imatinib, the tyrosine kinase inhibitor. Despite its superior clinical performance, imatinib drug resistance is developed in 20-30% patient, one of the causes is related to over expression of P-gp that transfer intracelluler imatinib to the extracelluler domain. P-gp is encoded by ABCB1 gene which is highly polymorphic. Three ABCB1 gene single nucleotide polymorphism (SNP), has been studied in CML patient; C1236T, C3435T, and G2677T/A. The most common mutation that can predict the clinical respond of imatinib therapy in Asian CML patient is C1236T mutation. This study purpose is to find the association between C1236T mutation in ABCB1 gene to the achievement of MMR in chronic phase.

Methods: This is a cross-sectional study using 120 blood samples of chronic phase CML patient who received imatinib mesylate for up to 12 months and met the selection criteria. The amplification process with PCR methods was performed, followed by Sanger methods of sequencing to determine the C1236T gene ABCB1 mutation.

Results: A total of 120 blood samples that met the selection criteria was obtained and analyzed. About 28,3% of chronic phase CML patient achieved the MMR. C1236T mutation was found in 72 patients (60%). There was no association between mutation and MMR achievement (prevalence risk 0,717 [0,275-1,461] p = 0,282]).

Conclusion: There was no association between C1236T gene ABCB1 mutation of chronic phase CML patient who received imatinib 12 months with the MMR achievement."