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Tri Yuliani
"Latar Belakang: Kardiomiopati uremikum adalah kelainan jantung yang didasari oleh kelainan pada ginjal dan merupakan penyebab kematian tertinggi pada pasien penyakit ginjal kronik (PGK). Overload cairan dan stres oksidatif berperan dalam patogenesis penyakit ini. Kuersetin adalah antioksidan yang bersifat kardioprotektif, namun belum ada data tentang efeknya pada kardiomiopati uremikum. Penelitian ini bertujuan untuk mengetahui efek kuersetin pada kardiomiopati uremikum menggunakan model nefrektomi 5/6 pada tikus.
Metode: Uremia diinduksi pada 3 kelompok tikus jantan Sprague-Dawley dengan nefrektomi 5/6, satu kelompok kontrol tanpa nefrektomi 5/6, masing-masing 6 ekor/kelompok dan diamati selama 8 minggu. Kelompok SNX tidak diberi pengobatan. Kelompok SNX+Q mendapat quersetin per oral dengan dosis 100 mg/kgBB/hari dan kelompok SNX+Cap mendapat kaptopril 10 mg/kgBB/hari. Hewan uji dikorbankan untuk diukur kadar malondialdehid (MDA) plasma dan jantung, aktivitas glutation peroksidase (GPX) jantung, NT-proBNP plasma, dan fibrosis jantung. Data dianalisis dengan uji ANOVA.
Hasil: Nefrektomi 5/6 menimbulkan sedikit fibrosis jantung, tidak mempengaruhi NT-proBNP, tidak mempengaruhi MDA jantung dan plasma dan meningkatkan secara bermakna aktivitas GPX jantung (p<0.05) sedangkan pemberian kuersetin dan kaptopril tidak mempengaruhi fibrosis jantung, tidak mempengaruhi NT-proBNP (p>0.05), tidak mempengaruhi MDA jantung dan plasma (p>0.05) dan tidak mempengaruhi aktivitas GPX jantung pada tikus uremia yang diinduksi dengan nefrektomi 5/6 (p>0.05).
Kesimpulan: Kuersetin tidak mempengaruhi fibrosis jantung dan fungsi jantung tikus uremia pasca nefrektomi 5/6. Peningkatan secara bermakna aktivitas GPX jantung pada semua kelompok pasca nefrektomi 5/6 (p<0.05) dibandingkan kelompok kontrol normal menunjukkan bahwa jantung tikus uremia masih berada pada fase kompensasi, yaitu mekanisme adaptasi jantung dan fungsi jantung belum terganggu meskipun terjadi sedikit fibrosis jantung.

Background: Uremic cardiomyopathy is a heart disease because of abnormalities in the kidneys that is the leading cause of death in patients with chronic kidney disease (CKD). Fluid overload and oxidative stress play an important role in its pathogenesis. Quercetin, as an antioxidant, has cardioprotective effect. To the best of our knowledge, its effect on uremic cardiomyopathy has not been investigated yet. This study aims to determine the effect of quercetin on uremic cardiomyopathy using 5/6 nephrectomy model in rats.
Methods: Uraemia was induced surgically in male Sprague-Dawley rats via 5/6 nephrectomy (SNX). Quercetin was administered per orally at a dose of 100 mg/kgBW/day for 8 weeks prior to sacrifice. Meanwhile captopril was administered per orally at a dose of 10 mg/kgBW/day. Oxidative stress was assessed using tiobarbituric acid reactive substances reaction then glutathione peroxidase (GPX) activity was determined to study on antioxidant mechanism. Myocardial fibrosis was analyzed using Massons? Trichrome staining and NTproBNP was measured as a marker of cardiac function. Data was analyzed using ANOVA.
Results: Nephrectomy 5/6 had no effects on plasma NT - proBNP, cardiac and plasma MDA, but induced mild myocardial fibrosis and increased cardiac GPX activity significantly (p<0.05). However, administration of quercetin and captopril had no effects on plasma NT - proBNP, cardiac and plasma MDA, myocardial fibrosis and GPX activity in uremic rats? heart induced by 5/6 nephrectomy.
Conclusion: Uremic rats? heart induced by 5/6 nephrectomy demonstrated mild myocardial fibrosis but preserved in vivo cardiac function. Increased GPX activity in uremic rats? heart compared to normal control (p<0.05) suggests induction of antioxidant defense mechanisms that might not be exhausted yet highlighting a compensatory phase which was unchanged following chronic either quercetin or captopril administration.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Tesis Membership  Universitas Indonesia Library
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Silalahi, Todung Donald Aposan
"Intervensi koroner perkutan (IKP) terbukti mengurangi morbiditas dan mortalitas penyakit jantung koroner (PJK). Cedera pembuluh darah akibat IKP dapat menyebabkan timbulnya inflamasi dan stress oksidatif. Studi ini menunjukkan bahwa kurkumin memiliki efek menekan inflamasi dan antioksidan pada penderita PJK stabil pasca-IKP. Penelitian ini bertujuan untuk mengetahui efektivitas suplementasi kurkumin per oral dalam menurunkan kadar inflamasi dan stres oksidatif pasca-IKP pasien PJK stabil.
Pasien dewasa PJK stabil dilakukan IKP, dirandomisasi secara acak tersamar ganda ke dalam kelompok kurkumin atau plasebo. Kurkumin (45 mg/hari) atau plasebo diberikan selama 7 hari sebelum IKP hingga 2 hari setelah IKP. Kadar marker inflamasi (hsCRP dan sCD40L) dan marker oksidatif (MDA dan GSH) dalam serum dinilai dalam 3 fase, 7 hari pra-IKP, 24 jam pasca-IKP, dan 48 jam pasca-IKP.
Selama periode April–Juni 2015, terdapat 50 pasien yang direkrut (25 kurkumin dan 25 plasebo) di RSUP Cipto Mangunkusumo dan RS Jantung Jakarta. Konsentrasi hsCRP dan sCD40L pada kelompok kurkumin dalam 3 fase cendrung menurun (p < 0,05) dibanding kelompok plasebo, tetapi konsentrasi hsCRP dan sCD40L pada tiap fase tidak berbedaan bermakna, sedang kadar MDA dan GSH tidak berbeda bermakna setiap fase, namun menunjukkan kecenderungan penurunan kadar MDA (p = 0,6) dan GSH (p = 0,3).
Pemberian kurkumin mempunyai kecenderungan menurunkan respons inflamasi pasca-IKP dan cenderung menghambat pembentukan stress oksidatif yaitu MDA serum melalui mekanisme peningkatan penggunaan antioksidan internal yaitu GSH serum.

Background: Percutaneous coronary intervention (PCI) has been proven to improve morbidities and mortalities in stable coronary heart disease (CHD). However, ischemia-reperfusion injury resulted from PCI might induce inflammation and oxidative stress. Several studies suggested that curcumin exerts anti-inflammatory and antioxidant properties that may be beneficial in post-PCI stable CHD patients.
Objectives: To determine the efficacy of orally administered curcumin in reducing inflammatory response and oxidative stress in post-PCI of stable CHD patients.
Methods: A double-blind randomized controlled trial consisting of 50 adult patients of both sexes with stable CHD who underwent PCI were treated with curcumin or placebo. Either curcumin (45 mg/day) or placebo was given 7 days prior to PCI until 2 days after PCI. Inflammatory markers (hsCRP and sCD40L) and oxidative stress assessment (MDA and GSH) were measured in 3 phases (7 days pre-PCI, 24 hours post-PCI, and 48 hours post-PCI).
Results: During April–June 2015, 50 patients were recruited (25 curcumin and 25 placebo) from Cipto Mangunkusumo General Hospital and Jakarta Heart Center. The serum concentrations of hsCRP and sCD40L in curcumin group (p < 0.05) in all observation phases were significantly lower compared with placebo group; however, there were no significant differences between groups. No significant difference was observed among phases in MDA and GSH, but there was a trend of decreasing MDA and GSH levels (p = 0.6 and p = 0.3, respectively) in curcumin group.
Conclusion: Curcumin tends to reduce inflammatory response following PCI by decreasing oxidative stress (MDA) through the increase of internal antioxidant utilization (GSH).
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Disertasi Membership  Universitas Indonesia Library
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Mona Oktarina
"ABSTRAK
Latar Belakang: Tujuan dari penelitian ini adalah untuk mengetahui pengaruh stres oksidatif pada ketahanan hidup spermatozoa manusia melalui peningkatan ekspresi caspase 3 dan aktivasi Akt. Informasi ini berhubungan dengan infertilitas laki-laki yang menurunkan viabilitas dan parameter kinetik spermatozoa.
Metode: Spermatozoa manusia diperoleh dari donor normozoospermia. Spermatozoa dimurnikan menggunakan larutan percoll. Spermatozoa dari seminal plasma dilarutkan dalam media Bigger, Whitter, dan Whittingham (BWW). Kemudian, spermatozoa diinkubasi dengan hidrogen peroksida (H2O2) 50 M, 100 M, 150 M, 200 M dan 250 M selama 2 jam. Stres oksidatif diuji dengan uji malondialdehid (MDA). Viabilitas diperiksa dengan larutan eosin Y. Parameter motilitas diukur dengan Computer Assisted Sperm Analyzer (CASA). Deteksi protein western blot akan dilakukan dengan antibodi anti-caspase-3 untuk mengenali caspase-3 dan antibodi phosphodetect yang mengenali fosforilasi Akt.
Hasil: Setelah inkubasi H2O2 selama 2 jam, terdapat efek H2O2 terhadap penurunan viabilitas dan motilitas (VAP, VSL, VCL) secara signifikan. Selain itu, viabilitas dan motilitas memiliki hubungan positif dengan proses apoptosis dan ketahanan hidup spermatozoa dengan menggunakan caspase 3 (meningkat) dan fosforilasi Akt (menurun) secara signifikan.
Kesimpulan: Stres oksidatif dapat menurunkan viabilitas dan kinetik spermatozoa melalui peningkatan ekspresi caspase-3 dan penurunan aktivitas Akt

ABSTRACT
Background: The purposes of this study was to evaluate the effect of oxidative stress on survival of human spermatozoa through releasing apoptotic process, This information has correlated with idiopathic infertility that decrease viability and motility parameters spermatozoa.
Methods: Human spermatozoa were obtained from normozoospermic volunteer donors. Spermatozoa was purified using discontinuous Percoll. Spermatozoa from the plasma seminal dissolved in Bigger, Written, and Whittingham (BWW) medium. Then, spermatozoa were incubated with 50 M, 100 M, 150 M, 200 M dan 250 M hydrogen peroxide (H2O2) for 2-h. Oxidative stress were assed by malondialdehyde (MDA) assay. Viability was examined by eosin Y solution. Kinectic parameters were assessed by Computer Assisted Sperm Analyzer (CASA). Detection of perotein in the western blot was examined with anti-caspase-3 antibodies to recognize caspase-3 activity and phsophodetect antibody that recognizes the phosphorylation of Akt.
Results: After 2-h incubation H2O2, there was dose dependent effect of H2O2 on viability and motility parameters significantly decrease. Therefore, viability and kinetic were positive relationship on apoptotic and survival effect by using caspase-3 activation (increase) and akt (decrease) significantly.
Conclusions: Oxidative stress can decreases viability and kinetic spermatozoa through increase caspse 3 and decrease Akt activation"
Depok: Fakultas Kedokteran Universitas Indonesia, 2019
T-pdf
UI - Tesis Membership  Universitas Indonesia Library
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Andi Arus Victor
"Latar Belakang: Stres oksidatif merupakan salah satu faktor patogenesis terjadinya retinopati diabetik (RD). Fotokoagulasi laser dan anti-VEGF bermanfaat pada penanganan RD. Keberhasilan terapi dan prognosis dapat dilakukan melalui penilaian klinis dan penanda biologis stres oksidatif.
Tujuan: Penelitian ini bertujuan membandingkan pengaruh fotokoagulasi laser dan bevacizumab intravitreal (BIV) terhadap penanda biologis stres oksidatif, antara lain aktivitas ALDH plasma, kadar VEGF, MDA dan aktivitas SOD vitreus pada penyandang RD proliferatif.
Metode: Penelitian ini adalah penelitian prospektif dengan desain uji klinis acak tersamar tunggal. Sebanyak 72 mata dari 69 penyandang RD proliferatif di Rumah Sakit Cipto Mangunkusumo (RSCM) antara Februari 2011 ? Juni 2013 dirandomisasi menjadi 4 kelompok terdiri dari kelompok 1) kontrol yaitu kelompok langsung vitrektomi sesuai indikasi (n = 18), 2) kelompok yang mendapat fotokoagulasi laser pre-vitrektomi (n = 18), 3) kelompok yang mendapat BIV pre-vitrektomi(n = 18) dan 4) kelompok yang mendapat kombinasi BIV dan fotokoagulasi laser previtrektomi (n = 18).
Hasil: Hasil penelitian ini mendapatkan bahwa pada kelompok 1, 2, 3 dan 4 masingmasing rerata aktivitas ALDH plasma (IU/mg protein) (0,034+0,02; 0,027+0,02; 0,025+0,02; 0,031+0,1; p = 0,66), kadar MDA vitreus (nmol/mL) (1,661+1,21; 1,557+1,32; 1,717+1,54; 1,501+1,09; p = 0,96), dan aktivitas SOD (U/mL) (0,403+0,50; 0,210+0,18; 0,399+0,49; 0,273+0,32 p = 0,38) dan tidak terdapat perbedaan bermakna, sedangkan perbandingan rerata kadar VEGF vitreus (pg/mL) (0,356+0,60; 0,393+0,45; 0,150+0,24; 0,069+0,13; p = 0,05) menunjukkan perbedaan yang bermakna. Kadar VEGF kelompok kombinasi BIV dengan fotokoagulasi laser lima kali lebih rendah dibandingkan dengan kelompok kontrol.
Simpulan: Kombinasi BIV dan fotokoagulasi laser tidak berpengaruh terhadap aktivitas ALDH plasma dan SOD vitreus, namun berpengaruh terhadap kadar MDA dan VEGF vitreus penyandang RD proliferatif. Kombinasi BIV dengan fotokoagulasi laser perlu dilakukan pada RD proliferatif. Pengukuran ALDH plasma dapat digunakan sebagai faktor prognostik untuk perubahan CMT dan visus.

Background: Diabetic Retinopathy (DR) is retinal vascular complications in patients with diabetes mellitus (DM). Oxidative stress plays a major role in the pathogenesis of this disease. The current management of DR includes laser photocoagulation (LF) and administration of anti-VEGF, such as intravitreal bevacizumab (IVB). Clinical parameters are usually applied in determining the outcomes of these methods of therapies. However, the measurement of biomarkers of oxidative stress can possibly be used to determine the prognosis.
Purpose: This study was aimed to compare the effect of LF, IVB and combined treatments on biomarkers of oxidative stress such as plasma ALDH and vitreal SOD activities, and vitreal VEGF and MDA level on proliferative DR patients.
Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital (RSCM) between February 2011 - June 2013 were randomized into 4 groups : 1) control group (n = 18), 2) LF previtrectomy group (n = 18), 3) IVB pre-vitrectomy group (n = 18) and 4) combined IVB and LF pre-vitrectomy group (n = 18). In all groups, the biomarkers of oxidative stress were measured as the primary outcome and visual acuity and CMT as secondary outcome.
Results: There were no statistically significant differences in the comparison of the average plasma ALDH activity (IU/mg protein) (0.034+0.02; 0.027+0.02; 0.025+0.02; 0.031+0.1; p = 0.66), vitreal MDA level (nmol/mL) (1.661+1.21; 1.557+1.32; 1.717+1.54; 1.501+1.09; p = 0.96) and SOD activity (U/mL) (0.403+0.50; 0.210+0.18; 0.399+0.49; 0.273+0.32 p = 0.38) among these four groups, respectively. However, the average of vitreal VEGF level (pg/mL) among these 4 group showed a statistically significant difference (0.356+0.60; 0.393+0.45; 0.150+0.24; 0.069+0.13; p = 0.05), with the level of vitreal VEGF in the combined group was 5 times lower than control.
Conclusion: Combined treatments of DR by IVB and LF does not have any effect on the activities of plasma ALDH and vitreal SOD. However, these combined treatments were correlated with lower vitreal MDA and VEGF level, higher SOD activity and lower VEGF level in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients. The measurement of plasma ALDH can be used as a prognostic factor for determining the visual acuity and CMT.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
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UI - Disertasi Membership  Universitas Indonesia Library
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Dwi Ramadhani
"Latar Belakang: Penelitian yang dilakukan bertujuan untuk mengetahui secara lebih mendalam mekanisme molekuler fenomena respons adaptasi pada penduduk Mamuju, Sulawesi Barat sebagai area radiasi latar tinggi (high background radiation area/HBRA) di Indonesia khususnya ditinjau dari jalur inflamasi dan stress oksidatif.
Metode: Penduduk Dusun Tande-Tande, Mamuju sebagai area radiasi latar tinggi dan penduduk Desa Topoyo, Mamuju Tengah sebagai kelompok kontrol direkrut dalam penelitian. Pemeriksaan kerusakan DNA, aberasi kromosom tidak stabil, stabil, mikronukleus, indeks mitosis, nuclear division index, aktivitas enzim SOD, GPx konsentrasi CAT serum dan darah lengkap dilakukan pada penelitian. Analisis G2 MN dilakukan untuk memvalidasi respons adaptasi pada penduduk Dusun Tande-Tande. Pengukuran konsentrasi sitokin dan protein pro-inflamasi, anti-inflamasi, p-Akt, Akt, dan NFkB dilakukan untuk mengetahui keterlibatan jalur inflamasi dan stress oksidatif pada fenomena respons adaptasi.
Hasil: Analisis kerusakan DNA, aberasi kromosom tidak stabil, stabil, aktivitas SOD, aktivitas GPx menunjukkan tidak terdapat perbedaan yang bermakna antara kedua kelompok penelitian. Rerata konsentrasi CAT kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Nilai indeks mitosis dan nuclear division index (NDI) pada kelompok kasus lebih tinggi secara bermakna dibandingkan kelompok kontrol. Rerata konsentrasi sitokin proinflamasi dan anti-inflamasi pada serum kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Rerata konsentrasi protein marker inflamasi CRP pada serum kelompok kasus lebih rendah tetapi tidak bermakna secara statistik dibandingkan kelompok kontrol. Hasil pemeriksaan darah lengkap memperlihatkan bahwa jumlah sel darah merah kelompok kasus lebih tinggi secara bermakna sedangkan jumlah limfosit, nilai MCV, MCH, MCHC, dan RDW kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Rerata nilai rasio p-Akt/Akt dan konsentrasi NFkB kelompok kasus lebih rendah secara bermakna dibandingkan dengan kelompok kontrol.
Kesimpulan: Fenomena respons adaptasi terhadap radiasi terjadi pada penduduk Dusun Tande-Tande, Mamuju. Hasil penelitian belum dapat membuktikan peningkatan antioksidan serta sitokin tertentu baik sitokin pro maupun anti-inflamasi pada kelompok kasus. Aktivasi jalur Akt dan NFkB pada kelompok kasus belum dapat dibuktikan mengingat nilai rasio p-Akt/Akt serta konsentrasi NFkB lebih rendah secara bermakna dibandingkan dengan kelompok kontrol.

Background: This study aim is to investigate the molecular mechanism of radioadaptive response in inhabitants of Mamuju, West Sulawesi as one of the high background radiation areas of Indonesia, particularly from inflammatory and oxidative stress perspectives.
Methods: Tande-Tande sub-village, Mamuju district inhabitants as high background radiation areas, and Topoyo Village inhabitants in Middle Mamuju district were recruited in this study. Evaluation of DNA damage, unstable and stable chromosomal aberrations, micronucleus, mitotic index, nuclear dividon index, SOD and GPx activities, serum catalase concentration and complete blood count were performed in this study. The G2 MN assay for validating the radioadaptive response phenomenon was performed in this study. Measurement of pro and anti-inflamamatory cytokines, p-Akt, AKt and NFkB were performed to find out the involvement of infllmation and stress oxidative on radioadaptive response phenomenon.
Results: The levels of DNA damage and stable and unstable chromosomal aberrations were not significantly different between the two groups. The rate of cell proliferation represented by the mitotic and nuclear dividion indexes showed a significantly higher rate in the case group. The SOD and GPx activities were not significantly different between the two groups. Interestingly, the CAT concentration was significantly lower in the case group. A significant lower level of both pro- and anti-inflammatory cytokines was also found in the case group. A lower level of CRP concentration as an inflammatory marker protein also showed in the present study, although it was not statistically significant. The complete blood counts analysis revealed a significant increase in RBC numbers and a significant decrease in lymphocyte numbers (MCV, MCH, MCHC, and RDW values) in the case group. The p-Akt/Akt ratio and NFkB concentration were also found to be statistically lower in the case group.
Conclusion: It can be concluded that the radioadaptive response phenomena induced by chronic low radiation dose exposure existed in Tande-Tande sub-village inhabitants. However, this present study failed to find a significant increase of antioxidant enzymes and inflammatory cytokines in Tande-Tande sub-village inhabitants. The activation of Akt and NFkB pathways in Tande-Tande sub-village inhabitants was also not found in this present study.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
D-pdf
UI - Disertasi Membership  Universitas Indonesia Library
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Jakarta: EGC, 1987
574.192 BIO
Buku Teks  Universitas Indonesia Library
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QU 4 Bio
Buku Teks  Universitas Indonesia Library
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