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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."

"The reaction of cis-[Pt(15NH3)2(H2O)2]2+ (3) with glutathione (GSH) was investigated in aqueous solution. In this reaction, the ammine in the platinum complex formed was liberated. Surprisingly two chelate rings were observed, six-membered-S,O-chelate ring complex cis-[Pt(15NH3)2(SG-S,O) (7) and five-membered-S,N-chelate ring complex cis-[Pt(15NH3)2(SG-S,N)] (8). The bis (thiolate) platinum(II) complex, cis-[Pt(15NH3)2(SG)2] (9) was always present in this reaction in any mole ratio used. The dinuclear sulphur-bridged complex (10), giving a broad peak in 15N NMR, was only present in very tiny amounts."

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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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"Latar Belakang: Periostin memainkan peran sebagai mediator proses inflamasi termasuk inflamasi dan fibrosis ginjal. Namun, data signifikansi periostin pada acute kidney injury terbatas. Kami meneliti korelasi kadar periostin urin dengan fungsi ginjal pada pasien keganasan yang mendapat terapi cisplatin dosis tinggi. Metode: Penelitian kohort prospektif ini dilakukan di n ruang rawat HOM lantai 8 gedung A, di RSCM dari November 2019 hingga jumlah sampel minimal terpenuhi dengan cara consecutive sampling. Data dianalisis menggunakan SPSS versi 23.0 sesuai tujuan penelitian. Hasil: Dari 37 responden diketahui 70,3% laki-laki, 29,7% berusia 41-50 tahun, 59,5% menderita KNF, serta 64,9% memiliki Skor Karnofsky 80. Kadar ureum dan kreatinin darah responden meningkat dari pra kemoterapi hingga 1 minggu paska kemoterapi I. Begitu juga dengan nilai eGFR yang makin menurun. Perubahan kadar periostin menurun selama kemoterapi I dan II, naik kembali 1 minggu paska kemoterapi III dengan nilai p>0,05. Pada uji korelasi kadar periostin urin dengan variabel fungsi ginjal lainnya tidak didapatkan domain yang signifikan bermakna (p>0,05) dengan nilai koefisien korelasi lemah (r = 0,017-0,254) dan beberapa domain memiliki arah korelasi negatif.Simpulan: Tidak didapatkan korelasi bermakna kadar periostin urin dengan kadar ureum darah, kreatinin darah serta laju filtrasi glomerulus pasien keganasan dengan terapi cisplatin dosis tinggi.

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Background: Periostin plays role as mediator of inflammatory processes including inflammation and kidney fibrosis. However, data on the significance of periostin in acute kidney injury are limited. We investigated the correlation of urine periostin levels with kidney function in malignant patients receiving high-dose cisplatin therapy. Methods: This prospective cohort study was conducted in the 8th floor HOM care room in building A, in the RSCM from November 2019 until the minimum sample size was fulfilled by consecutive sampling. Data were analyzed using SPSS version 23.0 according to the purpose of study. Results: Of the 37 respondents known to be 70.3% male, 29.7% aged 41-50 years, 59.5% suffer from NPC, and 64.9% have Karnofsky score of 80. Urea levels and blood creatinine of respondents increased from pre-chemotherapy to 1 week after chemotherapy I. Likewise, the eGFR value decreases. Changes in periostin levels decreased during chemotherapy I and II, rising again 1 week after chemotherapy III with a p value> 0.05. In the correlation test of urinary periostin levels with other kidney function variables, no significant domain was found (p> 0.05) with a weak correlation coefficient (r = 0.017-0.254) and some domains had a negative correlation direction.

Conclusion: No significant correlation was found in urine periostin levels with blood urea levels, blood creatinine and glomerular filtration rates of malignant patients with high-dose cisplatin therapy."

"Latar Belakang. Cisplatin masih merupakan agen pilihan utama untuk kemoradiasi pada pasien karsinoma nasofaring (KNF) stadium lanjut lokal. Acute Kidney Disaease (AKD) merupakan salah satu toksisitas utama pada cisplatin. Diketahui dosis kumulatif cisplatin berhubungan dengan kesintasan. Belum diketahui bagaimana hubungan dosis kumulatif cisplatin dengan AKD.Tujuan.Mengetahui hubungan dosis kumulatif cisplatin dengan kejadian AKDMetode Desain studi ini kohort retrospektif. Didapat subjek penelitian sebanyak 126 pasien KNF stadium lokal lanjut yang menjalani kemoradiasi di Rumah Sakit Cipto Mangunkusumo dalam rentang waktu Januari 2014 sampai Juni 2019. AKD didefinisikan sesuai kriteria Kidney Disease Improving Global Outcomes(KDIGO). Digunakan analisis bivariat menggunakan uji Kai Kuadrat untuk mengetahui hubungan antar variabel.Hasil. Penelitian ini melibatkan 126 pasien yang menjalani kemoradiasi pertama kali di Rumah Sakit Cipto Mangunkusumo (RSCM). Terdapat 49 (38,9%) pasien yang mengalami AKD. Tidak terdapat perbedaan bermakna kejadian AKD antara kelompok yang mendapatkan cisplatin dengan dosis kumulatif >200mg/m2 dan 200mg/m2 (39,5%vs38,0%,p=0,868, RR 1,039,CI 0,662-1,630).Kesimpulan. Proporsi AKD cukup tinggi (38,9%) , namun tidak terdapat perbedaan bermakna kejadian AKD antara dosis kumulatif cisplatin >200mg/m2 dengan 200mg/m2

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Background. Cisplatin is still the first choice agent for chemoradiation in localy advanced-stage Nasopharingeal Cancer (NPC) patients. Acute Kidney Disease (AKD) is one of the main toxicity in cisplatin. Known cumulative doses associated with survival. It is not yet known how the cisplatin cumulative dose relationship with AKD.

Objective. To determine the relationship of cisplatin cumulative dose with the incidence of AKD

Methods The design of this study was a retrospective cohort. There were 126 study subjects from advanced stage NPC patients who get chemoradiation at Cipto Mangunkusumo Hospital in the period of January 2014 to June 2019. AKD was in accordance with the Kidney Disease Improving Global Outcomes (KDIGO) study. Bivariate analysis using the chi Square test to find out the relationship between variables.

Results. This study found 126 patients who received chemoradiation for the first time at the RSCM. Obtained 49 (38,9%) patients who get AKD. Excluding the difference in the incidence of AKD between the groups receiving cisplatin with cumulative doses of >200 mg / m2 and 200 mg / m2 (39,5%vs38,0%,p=0,868,RR 1,039,CI 0,662-1,630)

Conclusion. The proportion of AKD is quite high (38,9%), but does not contain a significant difference with the AKD between the cumulative dose of cisplatin >200mg / m2 with 200mg / m2"

"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.

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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."

"Latar Belakang. Sebagian besar pasien kanker akan mengalami neuropati. Gejalaneuropatik yang muncul akibat kemoterapi dapat menghambat proses terapi.Cisplatin merupakan kemoterapi yang paling banyak digunakan dalam terapikanker nasofaring (KNF) dan banyak menyebabkan neuropati perifer. Penelitianini bertujuan untuk mengetahui gambaran neuropati pada pasien KNF yangmendapat kemoterapi di RSUPN Cipto Mangunkusumo serta faktor-faktor yangmempengaruhinya.Metode. Subyek penelitian ini adalah pasien KNF yang dikemoterapi dengancisplatin kurang dari 6 bulan sebelum pemeriksaan, baik tunggal, sebagaikemoadjuvant maupun kombinasi dengan kemoterapi lain yang tidakmenyebabkan neuropati perifer. Pasien Diabetes Mellitus serta gangguanneurologis sebelumnya disingkirkan dari penelitian. Dilakukan anamnesis,pemeriksaan fisik neurologis, dan elektroneurografi (ENG). Penelitian dilakukandengan menggunakan desain potong lintang. Pengumpulan data dilakukan padabulan Februari hingga Mei 2013.Hasil. Sebanyak 100 subyek penelitian yang terdiri dari 81 subjek laki-laki dan 19subyek perempuan diikutsertakan dalam penelitian ini. Usia dari subjek penelitianberkisar antara 30-60 tahun. Didapatkan 76% subjek mengalami neuropati, 51subjek diantaranya mengalami neuropati ENG, 25 subjek mengalami neuropatisecara klinis dan ENG. Didapatkan neuropati sensorik 82.89%, neuropati motorik80,26%, dan 51,32% mengalami neuropati otonom. Berdsarkan tipenya 89,47%mengalami degenerasi aksonal dan tidak satupun mengalami yang mengalamidemielinisasi murni. Secara statistik terdapat hubungan yang bermakna antara usiadan dosis dengan kejadia neuropati secara klinis (masing-masing p < 0,05).Kesimpulan. Telah didapatkan yang mendapat kemoterapi cisplatin di RSUPNCipto Mangunkusumo termasuk tinggi yaitu sebesar 76%, dan hanya 25% yangmengalami gejala neuropati secara klinis. Lebih dari setengah (51%) pasienmengalami neuropati subklinis prevalensi neuropati perifer. Neuropati sensorikmerupakan neropati paling banyak terjadi. Hampir semua pasien yang mendapatkemoterapi cisplatin mengalami neuropati aksonal. Usia lebih tua dan dosis totalyang lebih besar merupakan faktor-faktor yang mempengaruhi neuropati padapasien KNF yang mendapat kemoterapi cisplatin

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Background. The majority of cancer patients will experience neuropathy.

Neuropathic symptoms arising from chemotherapy can inhibit the therapeutic

process. Cisplatin is the most widely used chemotherapy in the treatment of

nasopharyngeal cancer (NPC) and the many causes of peripheral neuropathy. This

study aims to describe the neuropathy in NPC patients who received

chemotherapy in Cipto Mangunkusumo and the factors that influence it.

Method. The study subjects were NPC patients whose chemotherapy with

cisplatin less than 6 months before the examination, whether single, as

kemoadjuvant or in combination with other chemotherapy that does not cause

peripheral neuropathy. Diabetes Mellitus and patients with neurological disorders

previously excluded from the study. Anamnesis, neurological physical

examination, and elektroneurografi (ENG) were done. The study was conducted

using a cross-sectional design. The data was collected between February and May

2013.

Results. A total of 100 study subjects consisted of 81 male subjects and 19 female

subjects were included in this study. Age of study subjects ranged from 30-60

years. There were 76% of the subjects had neuropathy, 51 subjects had

neuropathy based on ENG only, 25 subjects based on clinical and ENG. There

were 82.89% had sensory neuropathy, 80.26% had motor neuropathy, and 51.32%

had autonomic neuropathy. Most (89.47%) had axonal degeneration and none had

the experience of pure demyelination. There is a statistically significant

relationship between age and dose with the incidence of clinical neuropathy (each

p <0,05).

Conclusion. The prevalence of neuropathy in cisplatin chemotherapy in NPC

patients in Cipto Mangunkusumo was as high as 76%, and only 25% who

experienced clinical symptoms. More than half (51%) patients had subclinical

neuropathy of peripheral neuropathy. Older age and greater total doses are all

factors that influence the KNF neuropathy in patients receiving cisplatin

chemotherapy."

"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.

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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. "

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