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Abstrak :
ABSTRAK
Secondary iron overload pada thalassemia mayor terjadi karena eritropoiesis inefektif dan tranfusi berkala. Besi melebihi transferin sehingga banyak non transferin bound iron NTBI yang mengkatalisasi terjadinya ion radikal bebas yang merusak jaringan. Pengendapan besi pada saluran cerna mengakibatkan perubahan fungsi, kerusakan organ, gangguan ketersediaan asam amino. Iron overload dikurangi dengan kelasi besi. Transferin merupakan kelator alami tubuh terdiri asam amino dominan alanin, leusin, glisin, asam aspartat. Berdasarkan penelitian, pasien iron overload memiliki transferin lebih rendah dibandingkan non iron overload. Penelitian bertujuan mengetahi perubahan status besi, profil asam amino dan hubungan iron overload dengan profil asam amino. Parameter yang diteliti : besi serum, unsaturated iron binding capacity UIBC , total iron binding capacity TIBC , feritin, saturasi transferin, indeks transferin, alanin, leusin, glisin, asam aspartat. Desain penelitian kohort dengan 21 subjek, yaitu 13 thalassemia beta mayor dan 8 thalassemia beta HbE. Hasil penelitian didapatkan perubahan status besi bermakna yaitu peningkatan feritin pasca transfusi, penurunan feritin pasca kelasi 1 bulan, peningkatan kadar besi pasca kelasi 3 bulan. Perubahan asam amino bermakna yaitu penurunan alanin, leusin, serta peningkatan glisin pasca kelasi 1 bulan Terdapat hubungan kuat, bermakna searah antara indeks transferin dan alanin pre transfusi. Terdapat hubungan kuat, bermakna, searah antara indeks transferin dengan alanin dan glisin pasca transfusi.

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ABSTRACT
Secondary iron overload in thalassemia major occurs due to ineffective erythropoiesis and periodic transfusions. The excess of iron exceed transferrin so there are many non transferrin bound iron NTBI that induce tissue damaging free radical ion. Accumulation of iron in intestine can lead to changes in the function, organ damage, lack of amino acid availability. Iron overload can be reduced by iron chelation. Transferrin is the body 39 s natural chelator comprising of dominant amino acid alanine, leucine, glycine, aspartic acid. Research found that transferrin were lower in iron overload patients. This study aims to acquire the changes of iron status, amino acid profile, and correlation between iron overload and amino acid profile. Studied parameter were serum iron, unsaturated iron binding capacity UIBC , total iron binding capacity TIBC , ferritin, transferrin saturation, transferrin index, alanine, leucine, glycine, aspartic acid. The study design were cohort with 21 subjects consisted of 13 beta major thalassemia and 8 beta Hbe thalassemia. The result showed significant iron status changes ferritin increased post transfusion, ferritin decreased after 1 month chelation and serum iron increased after 3 months chelation. Significant amino acid profile changes decreased of alanine and leucine, and glycin increased after 1 month chelation. There rsquo s significant correlation between transferrin index and alanine pre transfusion. There rsquo s significant correlation between transferrin index and alanine, glycine after 3 month chelation.

Abstrak :
Latar belakang: Indonesia memiliki prevalensi talasemia yang tinggi karena terletak dalam sabuk talasemia dunia. Iron overload seringkali terjadi pada pasien talasemia yang membutuhkan transfusi sehingga perlu diberikan kelasi besi. Akan tetapi, obat kelasi besi yang tersedia saat ini memiliki harga yang mahal dan menimbulkan banyak efek samping. Penelitian sebelumnya menunjukkan mangiferin berpotensi sebagai alternatif terapi kelasi besi namun bioavailibilitasnya rendah. Penelitian ini bertujuan menilai pengaruh pemberian mangiferin menggunakan nanopartikel kitosan-alginat terhadap aktivitas katalase di hati. Metode: Sebanyak 25 tikus Sprague-Dawley dibagi ke dalam 5 kelompok dengan perlakuan: Normal (N), Iron Overload (IO), dan terapi mangiferin (IO+M50); mangiferin-nanopartikel (IO+MN50, IO+MN25). Iron Dextran sebanyak 15 mg diinjeksikan secara intraperitoneal dua kali seminggu selama 4 minggu. Mangiferin dan mangiferin-nanopartikel diberikan secara oral setiap hari selama 4 minggu. Organ hati diperoleh dari organ tersimpan yang disimpan pada suhu -80°C. Aktivitas katalase pada hati diukur menggunakan Catalase Activity Assay Kit dan spektrofotometer. Analisis statistik dilakukan menggunakan uji Kruskal-Wallis (p=0,05) karena data tidak terdistribusi normal. Hasil: Penelitian ini menunjukkan tidak ada perbedaan aktivitas katalase yang bermakna di hati tikus antar tiap kelompok. Aktivitas katalase secara berurutan dari rendah ke tinggi adalah: kelompok IO+MN25 (0,00216 U/mg), IO+M50 (0,00221 U/mg), IO (0,00221), IO+M50 (0,0026 U/mg), dan N (0,00299 U/mg). Kesimpulan: Aktivitas katalase pada hati tikus Sprague-Dawley antar tiap kelompok tidak berbeda bermakna. ......Introduction: Indonesia has a high prevalent of thalassemia because of its location on world thalassemia belt. Iron overload often happens in transfusion dependent thalassemia patient in which iron chelation therapy is necessary. However, iron-chelating agents that available at this moment are expensive and have numerous adverse effects. Previous researches show that mangiferin could become an alternative iron-chelating therapy but has low bioavailability. This study aims to evaluate administration of mangiferin using chitosan-alginate nanoparticles on catalase activity in liver. Method: A total of 25 Sprague-Dawley rats were divided into 5 groups: Normal (N), Iron Overload (IO), and given with mangiferin therapy (IO+M50, IO+MN50, IO+MN25). Fifteenth milligrams of iron dextran were injected intraperitoneally, twice a week for 4 weeks. Mangiferin and mangiferin nanoparticles were orally given according to each group dose, every day for 4 weeks. Organ obtained by using stored organ that had been stored under -80°C cooler. Catalase activity on liver was measured using Catalase Activity Assay Kit and Spectrophotometer then analyzed by Kruskal-Wallis (p=0,05) because datas aren’t distributed normally. Result: This study shows there’s no significant catalase activity difference between each group. Katalase activity consecutively from lowest to highest are: IO+MN25 (0,00216 U/mg), IO+M50 (0,00221 U/mg), IO (0,00221), IO+M50 (0,0026 U/mg), and N (0,00299 U/mg). Conclusion: There’s no significant difference of catalase activity in Sprague-Dawley rat’s liver between each group.

Abstrak :
Prematuritas merupakan penyebab mortalitas dan morbiditas neonatus tertinggi. Sebagian besar prematur mendapat transfusi PRC berulang selama perawatan. Sementara itu, transfusi PRC berulang dapat meningkatkan kadar zat besi. Namun, hingga saat ini belum ada konsensus mengenai suplementasi besi pada prematur yang telah mendapat transfusi PRC berulang. Penelitian ini bertujuan untuk mengetahui status besi pada bayi prematur usia gestasi 28-32 minggu yang telah mendapat transfusi PRC berulang dan membuat rekomendasi mengenai pemberian suplementasi besi. Penelitian ini adalah penelitian kohort prospektif terhadap 70 bayi prematur yang lahir di RSCM bulan Maret 2021 – Mei 2021. Profil besi diperiksa usia kronologis 1, 2 dan 3 bulan. Hasil penelitian menunjukkan profil besi bayi prematur yang mendapat transfusi PRC > 2 kali lebih tinggi secara signifikan dibandingkan ≤ 2 kali (p<0,05). Titik potong total volume transfusi PRC yang menyebabkan status besi berlebih adalah PRC ≥ 50 mL/kgBB. Median feritin serum pada usia kronologis 1 bulan adalah 498,11 µg/L (358-885,62 µg/L), dua bulan adalah 232,66 µg/L (60,85-538,44 µg/L), tiga bulan adalah 42 µg/L (40,1-168,63 µg/L). Faktor risiko yang memengaruhi status besi berlebih pada bayi prematur adalah riwayat sepsis (OR 5,918 (IK 95%: 2,027-17,277)). Dari hasil penelitian disimpulkan bahwa bayi prematur yang mendapat transfusi PRC >2 kali memiliki profil besi yang lebih tinggi dibandingkan ≤ 2 kali pada usia kronologis 1 bulan. Bayi premtur yang mendapat transfusi PRC ≥ 50 mL/kgBB memiliki status besi berlebih di usia kronologis 1 bulan sehingga suplementasi besi sebaiknya diberikan pada usia kronologis 2 bulan. ......Prematurity is the most common cause of neonatal mortality and morbidity. Most of the preterm infants received multiple PRC transfusions during hospitalization. Meanwhile, multiple PRC transfusions can increase iron levels. However, to date there is no consensus regarding iron supplementation in preterm who have received multiple PRC transfusions. The objective of this study are to determine iron status in premature infants aged 28-32 weeks who have received multiple PRC transfusions and make recommendations regarding iron supplementation. This study is a prospective cohort study of 70 preterm infants born at the Cipto Mangunkusumo Hospital in March 2021 – May 2021. Iron profiles were examined chronologically age at 1, 2 and 3 months of age. The result are the iron profile of preterm infants who received PRC transfusion was > 2 times significantly higher than ≤ 2 times (p<0.05). The cut-off point for the total volume of PRC transfusion that causes iron overload status is ≥ 50 mL/kgBW. The median serum ferritin at 1 month of age was 498.11 g/L (358-885.62 g/L), two months was 232.66 g/L (60.85-538.44 g/L), three months is 42 g/L (40.1-168.63 g/L). The risk factor influencing iron overload status in preterm infants was a history of neonatal sepsis (OR 5.918 (95% CI: 2.027-17.277)). The conclusion of this study are preterm infants who received PRC transfusion >2 times had a higher iron profile than ≤ 2 times at 1 month chronological age. Preterm infants who received PRC transfusions ≥ 50 mL/kgBW had iron overload status at 1 month of chronological age and therefore iron supplementation should be given at 2 months of chronological age.

Abstrak :
Iron overload (IO) akibat transfusi darah jangka panjang pada penderita talasemia dapat berdampak fatal pada berbagai organ, termasuk pankreas. Akumulasi besi bebas serta kerusakan akibat stress oksidatif dapat menyebabkan resistensi insulin dan disfungsi sel β pankreas. Tanaman Phaleria macrocarpa yang mengandung mangiferin berpotensi sebagai agen pengkelat besi dan antioksidan. Penelitian ini bertujuan untuk menganalisis efek ekstrak etanol buah Phaleria macrocarpa terhadap kadar besi organ pankreas pada tikus model hemosiderosis. Sejumlah 30 ekor tikus Sprague-Dawley dibagi menjadi kelompok normal, deferiprone 462,5 mg/kgBB, kontrol negatif (IO), mangiferin 50 mg/kgBB, Phaleria macrocarpa 100 mg/kgBB dan 200 mg/kgBB. Injeksi intraperitoneal iron sucrose (15 mg) diberikan 2x seminggu selama 7 minggu untuk seluruh kelompok kecuali normal. Setelah pemberian terapi secara oral selama 4 minggu terakhir, kadar besi diukur dengan Atomic Absorption Spectrometry. Dosis total induksi besi 240 mg selama 7 minggu pada tikus model IO secara signifikan (p < 0,05) meningkatkan kadar besi pankreas sebesar 6 kali dibanding normal. Ekstrak etanol buah Phaleria macrocarpa dosis 100 dan 200 mg/kgBB cenderung menurunkan kadar besi organ pankreas pada tikus. Terdapat perbedaan yang signifikan (p < 0,05) antara kadar besi pankreas pada PM1 dan PM2. Tidak ada perbedaan yang signifikan antara kadar besi pankreas pada PM2 dengan normal. ......Iron overload due to long-term blood transfusion in thalassemia patients can cause fatal impacts on various organs, including the pancreas. Insulin resistance and pancreatic cell dysfunction may result from the accumulation of free iron and oxidative stress damage. Phaleria macrocarpa plants, which contain mangiferin, have potential as iron chelating agents and antioxidants. This study aimed to analyze the effect of Phaleria macrocarpa fruit ethanol extract on pancreatic iron levels in hemosiderosis model rats. Thirty Sprague-Dawley rats were divided into normal, deferiprone 462,5 mg/kgBB, negative control, mangiferin 50 mg/kgBB, and Phaleria macrocarpa extract at 100 and 200 mg/kgBB. 15 mg of iron sucrose was injected intraperitoneally twice a week for 7 weeks into all groups except normal. The iron level in the rat pancreas was assessed using AAS after 4 weeks of oral therapy. The total dose of 240 mg iron induction for 7 weeks in IO model rats significantly (p < 0,05) increased iron level 6x compared to normal. Phaleria macrocarpa ethanol extract at 100 and 200 mg/kgBB doses tended to decrease pancreatic iron level in rats. The difference in pancreatic iron level between PM1 and PM2 is significant (p < 0,05). PM2 and normal don't have significantly different pancreatic iron level.

Abstrak :

Latar belakang: Besi berlebih yang terakumulasi di dalam tubuh akibat transfusi darah berulang pada pasien talasemia-β mayor dapat menyebabkan kerusakan pada banyak organ, terutama hati. Besi berlebih di dalam tubuh dapat dikurangi kadarnya dengan agen kelasi besi. Mangiferin yang berasal dari sumber alami telah terbukti memiliki kemampuan sebagai agen kelasi besi, antioksidan, dan antiinflamasi. Namun, mangiferin memiliki bioavailabilitas yang rendah. Salah satu cara untuk meningkatkan bioavailabilitas mangiferin yaitu menjadikannya dalam formulasi kitosan-alginat nanopartikel. Penelitian ini bertujuan untuk membuktikan efek mangiferin dan mangiferin dalam kitosan-alginat nanopartikel pada gambaran histopatologi organ hati tikus yang diberi besi berlebih.

Metode: Dua puluh lima tikus Sprague-Dawley dibagi menjadi 5 kelompok: normal (N), kontrol negatif (KN), terapi mangiferin dosis 50 mg/kg BB/hari (M50), terapi mangiferin dalam kitosan-alginat nanopartikel dosis 50 mg/kg BB/hari (MN50), dan terapi mangiferin dalam kitosan-alginat nanopartikel dosis 25 mg/kg BB/hari (MN25). Setelah diberikan perlakuan selama 28 hari, tikus dikorbankan dan organ hati diambil untuk membuat preparat jaringan. Pengamatan dilakukan di bawah mikroskop dengan menggunakan uji lapang pandang. Parameter yang diteliti adalah gambaran nekrosis, inflamasi, dan steatosis hati.

Hasil: Pemberian mangiferin dapat memperbaiki kerusakan hati akibat besi berlebih dalam bentuk nekrosis, inflamasi, dan steatosis, secara signifikan (p <0,05) dibandingkan dengan kelompok KN. MN50 dan MN25 menunjukkan perbaikan yang signifikan pada nekrosis dan steatosis hati dibandingkan dengan M50. Kemampuan mangiferin dalam kitosan-alginat nanopartikel untuk memperbaiki nekrosis, inflamasi, dan steatosis hati, menunjukkan kecenderungan meningkat secara berurutan dari M50, MN50, dan MN25.

Kesimpulan: Mangiferin dalam kitosan-alginat nanopartikel lebih baik dalam memperbaiki gambaran histopatologi hati tikus yang diberi besi berlebih dibandingkan dengan mangiferin saja.

 

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Background: Iron overload that accumulates in the body due to repeated blood transfusions in β-thalassemia major can cause damage to many organs, especially the liver. Iron overload can be reduced by iron-chelating agents. Mangiferin from natural sources has been proven to have the ability as an iron-chelating agent, antioxidant and anti-inflammatory agent. However, mangiferin has a low bioavailability. To increase mangiferin bioavailability, formulated mangiferin in chitosan-alginate nanoparticles has been made. This study is aimed to determine the effect of mangiferin and mangiferin in chitosan-alginate nanoparticles on liver histopathology of iron overload rats.

Methods: Twenty-five Sprague-Dawley rats were divided into 5 groups: normal (N), negative control (KN), mangiferin therapy dose of 50 mg/kg BW per day (M50), mangiferin in chitosan-alginate nanoparticles therapy dose of 50 mg/kg BW per day (MN50), and mangiferin in chitosan-alginate nanoparticles therapy dose of 25 mg/kg BW per day (MN25). After treatment, the rats were sacrificed and the livers were taken to make preparations. Observations under the microscope were carried out using visual field test. The parameters studied were features of liver necrosis, inflammation, and steatosis.

Results: Mangiferin treatment can ameliorates the liver damage due to iron overload in the form of necrosis, inflammation, and steatosis, significantly (p < 0.05) compared to the KN group. MN50 and MN25 show significant amelioration in liver necrosis and steatosis compared to the M50. The ability of mangiferin in chitosan-alginate nanoparticles to ameliorates liver necrosis, inflammation, and steatosis, show a tendency to increase sequentially from M50, MN50, and MN25.

Conclusion: Mangiferin in chitosan-alginate nanoparticles ameliorates the liver histopathological features of iron overload rats better than mangiferin alone.

 

Abstrak :
Latar belakang: Kelebihan besi akibat transfusi darah terus-menerus dapat dialami penderita penyakit hemoglobinopati seperti talasemia. Di Indonesia, prevalensi penderita talasemia terbilang cukup tinggi. Untuk mengatasi kondisi tersebut, dibutuhkan terapi kelasi besi namun, terapi kelasi yang tersedia memiliki banyak kelemahan. Oleh karena itu, dilakukan studi terhadap mangiferin yang memiliki efek kelasi besi. Oleh karena bioavailabilitas mangiferin rendah, perlu dibentuk sebagai nanopartikel kitosan-alginat. Pada studi terdahulu, efek mangiferin dalam nanopartikel kitosan-alginat terhadap kadar MDA pada jantung tikus dengan kelebihan besi belum pernah dibuktikan Tujuan: Penelitian ini bertujuan untuk menilai kemampuan mangiferin dan mangiferin dalam nanopartikel kitosan-alginat terhadap kadar MDA organ jantung tikus dengan kondisi kelebihan besi Metode: Sebanyak 25 ekor tikus Sprague-Dawley dibagi dalam 5 kelompok: kontrol (N), tikus kelebihan besi (IO), dan kelompok terapi per oral yaitu tikus IO yang diberi mangiferin dosis 50 mg/kgBB (IO + M50), mangiferin nanopartikel kitosan-alginat dosis 50 mg/kgBB (IO + MN50), dan mangiferin nanopartikel kitosan-alginat dosis 25 mg/kgBB (IO + MN25). Tikus kelebihan besi diinjeksikan iron dextran intraperitoneal 15 mg, dua kali seminggu selama empat minggu. Kadar MDA organ jantung diukur menggunakan spektrofotometer. Hasil: Rerata kadar MDA jantung tikus pada kelompok N, IO, MN, MN50, dan MN25 secara berurutan adalah 7,36, 2,53, 5,64, 4,80, dan 9,36 nMol/mg. Tidak ditemukan penurunan kadar MDA pada kelompok terapi terhadap kelompok IO. Meskipun begitu, terdapat perbedaan signifikan kadar MDA jaringan jantung tikus Sprague-Dawley pada setiap kelompok (ANOVA, p = 0,048). Ditemukan juga perbedaan bermakna antara kelompok IO dengan MN (P= 0,03) dan MN 50 (P=0,041). Kesimpulan: Mangiferin dan mangiferin dalam nanopartikel kitosan-alginat tidak mampu menurunkan kadar MDA pada jantung tikus dengan keadaan besi berlebih. ......Introduction: Iron overload due to continuously blood transfusions is a problem that must be faced by people with hemoglobinopathy such as thalassemia. In Indonesia, the prevalence of patient with thalassemia is fairly high. To overcome the conditions of iron overload, iron chelator is needed. However, the available iron chelator therapy has many weaknesses. Therefore, a study of Mangiferin that has an iron chelator effect, has been conducted. However, the bioavailability of mangiferin is low so it needs to be formed as nanoparticles and wrap in chitosan-alginate. In previous studies, the mangiferin effect on MDA levels in the heart of rats with excess iron has not been measured Objective: This study aims to assess the ability of mangiferin and mangiferin in chitosan- alginate nanoparticles on MDA levels in the heart of rats with iron overload conditions. Method: Twenty-five Sprague-Dawley rats were divided into five groups: control (N), iron overload rats (IO), and an oral therapy group, IO rats treated with mangiferin 50 mg/kg/day per oral (IO+M50), mangiferin chitosan-alginate nanoparticle 50 mg/kg/day (IO+MN50), and mangiferin chitosan-alginate nanoparticle 25 mg/kg/day (IO+MN25).The rats were given Iron Dextran 15 mg intraperitoneal, twice a week for four weeks. MDA levels are measured in heart organs using a spectrophotometer. Result: The MDA concentration in heart at N, IO, MN, MN50, and MN25 groups were 7,36 nMol/mg, 2,53 nMol/mg, 5,64 nMol/mg, 4,80 nMol/mg, and 9,36 nMol/mg. There was no decline in MDA levels in the IO group compare to therapy group. However, there was a significant difference in MDA levels of the Sprague-Dawley mouse heart tissue in each group (ANOVA, P = 0.048). It was also found a significant difference between the IO group and MN (p = 0.03) and MN 50 (p = 0.041). Conclusion: Mangiferin and mangiferin in chitosan-alginate nanoparticles could not reduce MDA levels in the heart of mice with iron overload.

Abstrak :
ABSTRAK
Pendahuluan: Thalassemia adalah suatu kelainan genetik akibat kegagalan sintesis rantai globin, mengakibatkan terjadinya anemia berat akibat peningkatan aktivitas eritropoiesis yang inefektif dan hemolisis. Peningkatan aktivitas eritropoiesis akan memacu peningkatan absorpsi besi di usus sehingga terjadi kelebihan besi dalam tubuh. Transfusi darah dilakukan secara berkala untuk mengatasi anemia yang timbul pada pasien thalassemia mayor. Pemberian transfusi berulang akan mempercepat terjadi secondary iron overload, untuk mengatasinya diberikan terapi kelasi rutin.

Tujuan : Mendapatkan perubahan nilai indeks transferin, saturasi transferin, dan feritin sebelum dan sesudah transfusi dan juga sebelum dan sesudah terapi kelasi pada pasien thalassemia mayor. Mendapatkan perbedaan indeks transferin dan saturasi transferin, dan feritin sebagai parameter untuk menilai perubahan status besi pada pasien thalassemia mayor pasca transfusi dan terapi kelasi.

Metode: Desain penelitian kohort prospektif. Subjek penelitian terdiri dari 35 pasien thalassemia mayor usia 7-18 tahun yang mendapat transfusi berulang dan kelator besi rutin. Dilakukan pemeriksaan kadar besi serum, UIBC, TIBC, feritin, transferin, saturasi transferin dan indeks transferin pre transfusi, pasca transfusi dan pasca terapi kelasi.

Hasil: Rerata indeks transferin pasca transfusi 124±22 % lebih rendah secara bermakna dari pre transfusi dengan nilai p=0,016, sedangkan pasca kelasi 123 ± 34.5 % (p=0,045). Saturasi transferin pasca transfusi 96 (51 – 100)% meningkat secara bermakna dibangdingkan pre transfusi 87(69-100)% dengan nilai p=0,026, namum tidak berbeda bermakna pada pasca kelasi 87 (39-100). Kadar feritin serum pasca transfusi 3737 (649 -17.094) mg/dL, meningkat secara bermakna dibandingkan pre transfusi 3315 (544,7-14.964) mg/dL (p=0,018). Perbedaan indeks transferin dan saturasi transferin pre transfusi 45(22-153)% lebih tinggi secara bermakna dibandingkan pasca transfusi 35(6-89)% dengan nilai p=0,000, sedangkan pasca kelasi adalah 41±25 dengan nilai p=0,036.

Kesimpulan: pemeriksaan indeks transferin untuk pemantauan efektifitas terapi kelasi pada pasien thalasemia mayor dapat dipertimbangkan.

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ABSTRACT
Introduction. β thalassemia syndromes are a group of hereditary disorder characterized by genetic deficiency in the synthesis of β-globin chains. It is associated in severe anemia caused by an increase in ineffective erythropoiesis activity and hemolysis. Erythropoiesis activity will spur increased iron absorption in the intestine so there will be an excess of iron in the body. Blood transfusion is used routinely to treat anemia arising in patients with thalassemia major. Repeated transfusion will accelerate occur secondary iron overload, to solve given chelation therapy routine.

Objective :To know the index value changes transferrin, transferrin saturation, and ferritin before and after transfusion and also before and after chelation therapy in patients with thalassemia major. To know difference transferrin index and transferrin saturation, and ferritin as a parameter to assess changes iron status in patients thalassemia major post-transfusion and chelation therapy.

Methods. This was prosphective cohort, There were 35 patients with thalassemia major who receive repeated transfusions and iron kelator routine, with age 7-18 years. Examination of serum iron levels, UIBC, TIBC, ferritin, transferrin, transferrin saturation and transferrin index before transfusion, after transfusion, and after chelation therapy.

Results. Mean transferrin index post-transfusion 124±22% was significantly lower than pre transfusion (p=0.016), as well as post-chelation 123±34.5% with a value of p=0.045. Transferrin saturation post-transfusion 96 (51-100)% increased significantly with pre transfusion 87 (69-100)% with a value of p=0.026, However no significant difference were observed in post chelation therapy 87 (39-100). Post-transfusion serum ferritin level 3737 (649-17094) mg/dL, increased significantly compared to pre transfusion 3315 (544.7-14,964) mg/dL (p=0.018). Differences transferrin index and transferrin saturation pre transfusion was 45 (22-153)% significantly higher than the post-transfusion 35 (6-89)% with a value of p=0.000, while the post chelation thyrapy was 41±25% (p=0.036).

Conclusion. Transferrin index can be considered for monitoring the effectiveness of chelation therapy in patients with thalassemia major.

Abstrak :
Latar belakang: Iron overload pada penderita talasemia memicu terbentuknya Reactive Oxygen Species dalam tubuh. Sel tubuh secara alami mempunyai mekanisme dalam menangkal radikal bebas dan antioksidan, salah satunya dengan mengaktifkan enzim katalase. Mangiferin adalah bahan alami yang terbukti mempunyai efek anti oksidan dan pengkelat besi, Namun dari hasil penelitian membuktikan bahwa bioavailabilitas mangiferin kecil. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian mangiferin dalam nanopartikel kitosan-alginat terhadap aktivitas enzim katalase pada jantung tikus yang diberi besi berlebih. Metode: Organ jantung tikus Sprague-Dawley yang didapat dari penelitian sebelumnya, dibuat dalam bentuk homogenat dan dibagi menjadi lima kelompok, yaitu: kelompok normal , kelompok Iron Overload , dan kelompok yang diberi besi berlebih dengan terapi mangiferin 50 mg/kg BB, mangiferin nanopartikel 50 mg/kg BB dan mangiferin nanopartikel 25 mg/kg BB. Homogenat digunakan untuk pengukuran kadar protein dengan metode Bradford dan aktivitas enzim katalase diukur dengan Catalase Activity Assay Kit. Hasil: Pada penelitian ini, dengan uji Kruskal-Wallis, didapatkan nilai p sebesar 0.05, yang berarti tidak didapatkan perbedaan aktivitas katalase jantung yang bermakna antar tiap kelompok. Aktivitas katalase jantung tertinggi ditemukan pada kelompok normal dengan nilai sebesar (0,1580 ± 0,1371) U/mg, diikuti kelompok mangiferin nanopartikel 25 (0,0336 ± 0,0137), kelompok mangiferin 50 (0,0209 ± 0,0127), kelompok Iron overload (0,0137 ± 0,0041) dan kelompok mangiferin nanopartikel 50 (0,0129 ± 0,0031). Kesimpulan: Tidak terdapat penurunan aktivitas katalase yang bermakna pada organ jantung tikus pada pemberian mangiferin dalam nanopartikel kitosan-alginat dibandingkan dengan pemberian mangiferin saja maupun antara mangiferin nanopartikel yang diberikan dengan dosis yang berbeda. ......Background: Iron overload in thalassemic patients triggers the formation of Reactive Oxygen Species in the body. Body cells naturally have mechanisms to fight against free radicals and antioxidants; one of them is the activation of Catalase enzymes. Mangiferin is a natural substance proven to have antioxidant and iron binding properties. Nevertheless, results from studies show that the bioavailability of Mangiferin is modest. The objective of this study is to find out the effect of Mangiferin administration in Chitosan-Alginate nanoparticles on the Catalase Enzyme in the hearts of rats given an overload of iron. Method: The hearts of the Sprague-Dawley rats were obtained from the previous study, made in the homogenate form and divided into five groups namely the normal group, Iron Overload, and the groups given an overload of iron by giving the therapy of Mangiferin with the dose of 50mg/kg of body weight, Mangiferin nano particles 50 mg/kg of body weight and Mangiferin nano particles 25 mg/kg of body weight. Homogenate was used to measure the protein concentration with the method of Bradford and Catalase enzyme activity was measured by Catalase Activity Assay Kit. Result: In this study, with the Kruskal Wallis testing, p value is not less than 0,05, meaning there was no significant difference in the cardiac catalase activity among the groups. The highest cardiac catalase activity was encountered in the normal group with the value (0,1580 ± 0,1371) U/mg, followed by the mangiferin nanoparticles 25 group (0,0336 ± 0,0137), mangiferin 50 group (0,0209 ± 0,0127), Iron overload group (0,0137 ± 0,0041) and mangiferin nanopartikel 50 group (0,0129 ± 0,0031). Conclusion: There was no significant reduction in the catalase activity in the hearts of the rats in the mangiferin group with the chitosan alginate nanoparticles compared with the group with were administration of mangiferin as well as among the mangiferin nanoparticle groups in diverse doses.

Abstrak :
Latar Belakang: Sampai saat ini belum ada terapi yang digunakan untuk mencegah iron overload pada pasien talasemia. Studi terdahulu menunjukkan bahwa ekstrak daun Mangifera foetida L. dapat menurunkan kadar besi pada model iron overload in vitro dan in vivo. Penelitian ini bertujuan untuk mengetahui efikasi ekstrak daun Mangifera foetida L. dalam mencegah terjadinya iron overload pada tikus yang diinduksi besi. Metode: Tiga puluh tikus Sprague-Dawley jantan dibagi menjadi 5 kelompok yaitu kelompok normal (tidak diberi perlakuan), kelompok iron overload (IO) dan kelompok dosis setara mangiferin (DSM) 50,100, dan 200 mg/kg BB. Kelompok IO, DSM 50, DSM 100, dan DSM 200 diberikan bersama dengan induksi Fe dekstran secara intraperitonial 15 mg seminggu dua kali selama 4 minggu. Sebelum dan sesudah 4 minggu percobaan hewan coba diambil darah dan urinnya. Setelah 4 minggu hewan coba diterminasi dan diambil organ limpa, hati, dan jantung. Pemeriksaan yang dilakukan adalah aktivitas SOD plasma, Fe urin, Fe limpa, Fe plasma, kadar mangiferin darah, dan kadar ferritin darah. Hasil: Ekstrak daun Mangifera foetida L. tidak dapat mencegah kenaikan Fe di plasma, dan limpa. Terjadi penurunan aktivitas SOD, yang disertai dengan peningkatan konsentrasi ferritin. Kesimpulan: Ekstrak daun Mangifera foetida L. tidak terbukti dapat mencegah peningkatan kadar besi, ferritin dan penurunan aktivitas antioksidan pada tikus yang diinduksi besi.

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Introduction: Presently, there is no available agent for the prevention of iron overload in thalassemia patients. Previous studies had shown that Mangifera foetida L. leaves extract reduced the levels of iron in iron overload in vitro and in vivo models. The present study aimed to determine the efficacy of Mangifera foetida L. leaves extract in the prevention of iron overload in the rats induced with iron. Methods: Thirty male Sprague-Dawley rats were divided into 5 groups treated with: none (untreated), iron overload (IO), equivalent dose group mangiferin (DSM) 50, DSM 100 and DSM 200 mg / kg BB. Fe dextran 15 mg intraperitoneal twice weekly for 4 weeks were given together with IO group, DSM 50, DSM 100 and DSM 200. Urine and blood samples were taken before and after treatments. After 4 weeks of treatment, rats were terminated and samples of spleen, liver, and heart were taken. SOD activities were done in plasma, Levels of Fe were determined in plasma, urine and spleen, while Ferritin and mangiferin levels were determined from plasma. Results: Mangifera foetida L. leaves extract did not prevent the increase of Fe plasma, and spleen. SOD activities were shown to decrease, along with the increase of ferritin concentrations. Conclusion: Mangifera foetida L. leaves extract could not prevent the increased levels of iron, ferritin and decreased antioxidant activity in rats induced by iron.

Abstrak :
Latar belakang: Iron overload adalah kondisi dimana terjadi penumpukan besi berlebih dalam tubuh dan sering terjadi pada pasien yang menjalani transfusi berulang seperti pasien talasemia beta mayor. Iron overload ini merusak banyak organ dan salah satunya yang terberat adalah kerusakan organ jantung berupa kardiomiopati yang merupakan penyebab utama kematian pasien talasemia beta mayor. Tatalaksana yang diberikan untuk mencegah iron overload adalah obat pengkelat besi yang saat ini harganya mahal dan banyak efek samping. Mangiferin adalah senyawa polifenol yang dapat dijadikan kandidat potensial obat pengkelat besi. Sayangnya bioavailabilitasnya rendah, sehingga dipikirkan pembuatan formulasi mangiferin dalam nanopartikel kitosan alginate akan dapat meningkatkan bioavailabilitas dan distribusinya ke organ. Pada penelitian ini mangiferin akan diukur kadarnya dalam organ jantung tikus Sprague- Dawley yang diberi besi berlebih. Metode: Data penelitian ini diperoleh dari homogenat organ jantung tersimpan tikus Sprague- Dawley yang diperoleh dari penelitian sebelumnya sebanyak 17 sampel dan diukur kadar Mangiferin dalam jantung menggunakan alat HPLC. Tikus dibagi ke dalam tiga kelompok dan diinduksi besi berlebih sambil diberikan Mangiferin yang berbeda setiap harinya yaitu Mangiferin konvensional 50 mg/ kgBB (MK50), Mangiferin kitosan alginat 50 mg/ kgBB (MN50), dan Mangiferin kitosan alginat 25 mg/ kgBB (MN25). Hasil: Nilai rerata kadar MK50, MN50 dan MN25 yang diukur dalam organ jantung tikus dalam satuan (ng/g) berturut-turut sebesar 4365,80, 4453,65 dan 4171,97 dengan nilai p = 0, 974. Simpulan: Kadar mangiferin di jantung tikus Sprague-Dawley yang diinduksi besi berlebih setelah pemberian mangiferin kitosan alginate nanopartikel tidak berbeda dengan pemberian mangiferin konvensional. ......Background : Iron overload is an accumulation of excess iron in the body and often occurs in repeated transfusion patients such as beta thalassemia major. Iron overload damages multi-organs and the worst impact is cardiomyopathy which is the main cause of death in beta thalassemia major patients. The preventive treatment for iron overload is iron chelating drugs, which are expensive and have many adverse effects. Mangiferin is a polyphenol that have potential to be a candidate for iron chelator. Unfortunately, its bioavailability is low. Therefore, new formulation is considered to increase the bioavailability of Mangiferin with chitosan alginate nanoparticles technology which was measured in the heart organ of iron overload Sprague-Dawley rats. Method : The data of this study were obtained from the stored heart organ homogenate of Sprague-Dawley rats which were obtained from a previous study of 17 samples and the levels of mangiferin in the heart were measured using an HPLC device. Rats were divided into three groups and induced by excess iron while given different Mangiferin every day, namely conventional Mangiferin 50 mg/kgBW (MK50), Mangiferin chitosan alginate 50 mg/kgBW (MN50), and Mangiferin chitosan alginate 25 mg/kgBW (MN25). Results: The mean values of MK50, MN50 and MN25 levels measured in the rat heart in units (ng/g) were 4365.80, 4453.65 and 4171.97 with p = 0.974, respectively. Conclusion: There was no significant difference between Conventional Mangiferin and Mangiferin Nanoparticles in the heart of Sprague-Dawley rats induced by excess iron.