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Abstrak :
Latar Belakang: Penyakit Ginjal Kronik PGK merupakan masalah kesehatan di seluruh penjuru dunia. PGK menjadi penyebab menurunnya kualitas hidup penderitanya sekaligus meningkatkan risiko kematian. Penyakit Ginjal Kronik ditandai dengan terjadinya kerusakan ginjal dalam waktu lama dan progresif. Gangguan pada PGK berkaitan dengan kejadian stres oksidatif, yaitu keadaan di mana Reactive Oxygen Species ROS terbentuk melebihi pertahanan antioksidan. Kuersetin sebagai bagian keluarga flavonoid diketahui memiliki aktivitas antioksidan. Penelitian sebelumnya mendapatkan bahwa pemberian kuersetin mampu meningkatkan ekspresi protein Nuclear factor related erythroid factor 2 Nrf2 di dalam nukleus pada tikus yang mengalami PGK. Penelitian ini merupakan penelitian lanjutan untuk mengkonfirmasi apakah peningkatan ekspresi protein Nrf2 di dalam nukleus terjadi pada tahap transkripsi. Metode: Jaringan ginjal tikus Sprague-Dawley dari penelitian terdahulu yang tersimpan pada suhu -80oC, diukur ekspresi mRNA Nrf2, Keap1dan HO1menggunakan qRT PCR. Terdapat 4 kelompok penelitian yaitu kelompok kontrol normal, kelompok dengan nefrektomi 5/6 berturut-turut diberi CMC 0,5 , kaptopril 10 mg/kgBB, dan kuersetin 100 mg/kgBB. Ekspresi mRNA Nrf2, Keap1 dan HO1dianalisis statistik menggunakan uji ANOVA yang dilanjutkan dengan multiple comparison post hoc dengan LSD, Kruskal-Wallis untuk data yang tidak memenuhi syarat uji ANOVA dimana perbedaan dianggap bermakna secara statistik bila p.

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Background Chronic Kidney Disease CKD has been a problem all around the world as it causes the decrease of life quality and also raises the risk of death. Chronic kidney disease characterized with long time and progressively kidney failure. The alteration of CKD correlated to oxidative stress, a condition when Reactive oxygen species ROS produced more than antioxidant defense. Quercetin as a part of flavonoid, has been known to have an antioxidant activity. It has been showed in the previous study that quercetin increased intra nuclear Nuclear factor related erythroid factor 2 Nrf2 . This study proposed to confirm whether the increase of nuclear NRF2 is happened in transcription event. Method Kidney tissue of Sprague Dawley rat from previous study which had been saved in 80oC had measured the expression of Nrf2, Keap1 and HO1 mRNA by qRT PCR. There were 4 groups as the previous study, normal control group, 5 6 nephrectomy plus consecutively 0,5 CMC, 10 mg kgBW captopril, and 100 mg kgBW quercetin. Expression of Nrf2, Keap1 and HO1 mRNA had been analyzed statistically with ANOVA test and LSD multiple comparison post hoc. For data that are not fit to analyzed with ANOVA would be analyzed with Kruskal Wallis and Mann Whitney. The data considered as significantly different by p.

Abstrak :
ABSTRACT
Latar Belakang: Prevelansi gagal ginjal kronis semakin meningkat di Indonesia dan di seluruh dunia. Salah satu sumber utama morbiditas dan mortalitas pada gagal ginjal kronis adalah komplikasi penyakit kardiovaskular. Mastin adalah suplemen yang diproduksi di Indonesia terbuat dari ekstrak kulit buah manggis yang dilaporkan memiliki kemampuan antioksidan, anti-inflamasi dan antitumor. Penelitian ini bertujuan untuk menyelidiki apakah Mastin mampu meningkatkan respon antioksidan dalam hati tikus yang gagal ginjal kronis dengan mengukur ekspresi Nrf2, master regulator Antioxidant Response Element ARE Metode: RNA diekstrak dari jaringan jantung dari 3 kelompok tikus: Kelompok Normal, kelompok nefrektomi dan kelompok nefrektomi dengan Mastin . Kemudian dilakukan prosedur Two step real-time RT-PCR untuk menghitung ekspresi relatif gen Nrf2. Hasil: Ekspresi Nrf2 sangat menurun pada kelompok nefrektomi sedangkan pada kelompok nefrektomi dengan Mastin , ekspresi tersebut hanya sedikit meningkat. Kesimpulan: Gagal ginjal kronis mengakibatkan gangguan dalam aktivasi Nrf2 dalam hati. Meskipun terdapat sedikit peningkatan ekspresi Nrf2 setelah pemberian Mastin , hasil tersebut tidak cukup signifikan untuk memberikan efek kardioprotektif melewati jalur Nrf2.

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ABSTRACT
Background Chronic kidney disease CKD is increasingly prevalent in Indonesia and around the world. One of the major sources of morbidity and mortality in CKD is the complication of developing cardiovascular disease. Mastin is a locally produced supplement made from extract of mangosteen pericarp which is reported to have antioxidative, anti inflammatory and antitumor properties. This research aims to investigate whether Mastin is capable of improving antioxidant responses in the heart during CKD by measuring the expression of Nrf2, a master regulator of antioxidant response elements. Method RNA was extracted from heart tissue of 3 groups of rats Normal group, Nephrectomy group and Nephrectomy with Mastin group. Two Step real time RT PCR was then conducted to calculate the relative expression of Nrf2 gene. Results Expression of Nrf 2 was markedly decreased in the Nephrectomy group but slightly increased in the Nephrectomy with Mastin group. Conclusions Chronic Kidney Disease resulted in impaired activation of Nrf2 pathway in the heart. Although the administration of Mastin slightly increased Nrf2 expression, it is not significant enough to confer cardioprotective effects through the Nrf2 pathway.

Abstrak :
Latar Belakang: Hipoksia kronik merupakan salah satu penyebab penyakit ginjal antara lain akibat iskemia kronik, anemia serta peningkatan pembentukan Reactive Oxygen Species (ROS) di dalam sel. Penggunaan obat jangka panjang untuk mengurangi faktor risiko hipoksia pada ginjal yaitu Angiotensin-Converting Enzyme inhibitors dan Angiotensin Receptor Blockers akan menimbulkan efek samping yang berat. Pemberian kombinasi ekstrak air akar Acalypha indica 250 mg/KgBB (AI250) dan herba Centella asiatica 150 mg/kgBB (CA150) menunjukkan efek neuroterapi sel neuron pada tikus Spraque Dawley pascahipoksia. Atas dasar penelitian tersebut akan dibuktikan manfaat kombinasi ekstrak etanol (akar AI+ herba CA) dan/atau ekstrak tunggalnya dalam memperbaiki kerusakan ginjal tikus Spraque Dawley pascahipoksia melalui mekanisme antioksidan. Metode: 28 ekor tikus Sprague Dawley jantan yang dibagi ke dalam 7 kelompok yaitu normal; hipoksia+air; hipoksia+kombinasi1; hipoksia+kombinasi2; hipoksia+tunggal1; hipoksia+tunggal2; hipoksia+vit C. Induksi hipoksia dilakukan selama 7 hari dalam hypoxic chamber diisi O2 10 % dan N2 90 % bertekanan 1 atm. Pada hari ke-8 pascareoksigenasi 1 jam masing-masing kelompok diberi perlakuan air; (AI200+CA150); (AI250+CA100); AI250; CA150 dan vitamin C peroral selama 7 hari. Pada akhir studi hewan coba diterminasi menggunakan eter. Darah dan organ ginjal diambil untuk pemeriksaan kadar MDA, ekspresi relatif mRNA HIF-1α, kadar kreatinin dan urea plasma serta pemeriksaan histopatologi. Hasil: Pemberian ekstrak etanol kombinasi (AI250+CA100) dapat menurunkan kadar MDA ginjal dan plasma secara bermakna dibandingkan kontrol hipoksia (p=0,001dan p=0,021) dan ekstrak etanol AI 250 (p=0,003 dan 0,043). Pada kombinasi ekstrak AI250+CA100 terjadi penurunan ekspresi relatif mRNA HIF-1α (p=0,014). (AI250+CA100), penurunan kadar urea plasma (p=0,001) dan perbaikan lesi intra- glomerulus p=0,013. Kesimpulan: Kombinasi ekstrak etanol (AI250+CA100) dan tunggal (AI250) memiliki aktivitas antioksidan terbaik sehingga dapat mencegah kerusakan ginjal pascahipoksia, secara biokimiawi dan gambaran histopatologinya.

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Background: The Chronically hypoxia can be caused by chronic ischemia, anemia and increased formation of Reactive Oxygen Species (ROS) in the cell. Existing treatments for long term in order to reduce the risk factors in kidney hypoxia (Angiotensin Converting Enzyme inhibitor and Angiotensin Receptor Blockers) can cause severe side effects. Using combination of water extract of the root of Acalypha indica 250 mg/KgBB (AI250) and herbaceus Centella asiatica 150 mg/kgBB (CA150) showed the effect of neuronal cell neurotherapy in Spraque Dawley Rat post-hypoxic. On the basis of this studies wil be proven benefits of the ethanolic extract in combination and single of the Root of Acalypha indica and Herbaceus Centella asiatica Supplementation in repairing at Spraque Dawley rat kidney damage post-hypoxic through an antioxidant mechanism. Methode: 28 Male Sprague-Dawley rats were divided into 7 groups: normal control; hypoxia + water control; hypoxia + combination 1; hypoxia + combination 2; hypoxia + single 1; hypoxia + single 2; hypoxia + vitamin C. Induction of hypoxic for 7 days in a hypoxic chamber filled with 10% O2 and 90% N2 pressure of 1 atm. On the 8 th day pasca reoxygenation for 1 hour, each group were treated by water; (AI200 + CA150); (AI250 + CA100); AI250; CA150 and vitamin C orally for 7 days. At the end of the test animal studies using ether terminated. Blood and kidneys were taken for examination MDA levels, the relative mRNA expression of HIF-1α, plasma urea and plasma creatinine levels and histopathology. Result: Combination of ethanolic extract (AI200+CA150) decreased MDA levels kidney tissue and plasma were significantly compared with the control (p = 0,001dan p = 0.003) and ethanolic extract AI 250 (p = 0.016 and 0.043), AI250 + CA100 decreased relative mRNA expression HIF-1α (p = 0.014). The combination of extracts (AI250 + CA100) decreased plasma urea levels (p = 0.001) and the repair of intra-glomerular lesions p = 0.013. Conclusion: the combination (AI250+CA100) and single (AI250) administration has the best antioxidant activity, thus preventing kidney damage post hypoxic by biochemical parameters and histopathology.