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"Kelebihan besi dapat menyebabkan kerusakan organ akibat pembentukan radikal bebas dan ferroptosis, terutama pada hati sebagai organ utama penyimpanan besi. Efikasi deferiprone sebagai kelator standar yang paling banyak digunakan di Indonesia untuk menurunkan kadar besi hati masih tidak adekuat dan memiliki potensi hepatotoksik. Penelitian ini bertujuan untuk melihat efek kombinasi deferiprone dengan ekstrak etanol buah Phaleria macrocarpa (PM) yang sudah terbukti mampu mengkelat besi untuk mengatasi kelebihan besi pada tikus model hemosiderosis serta melihat interaksi senyawa aktif ekstrak PM dengan transporter uptake besi (DMT-1 dan ZIP-14) secara in-silico. Tikus dibagi menjadi enam kelompok, yaitu normal (N), kontrol negatif (KN), deferiprone (D), kombinasi deferiprone dosis lazim+ekstrak PM (DPM1) dan kombinasi deferiprone setengah dosis lazim+ekstrak PM (DPM2). Induksi kelebihan besi dilakukan dengan injeksi iron-dextran (intraperitoneal) selama 8 minggu. Terapi dimulai pada minggu ke-4 hingga ke-8. Parameter yang diukur meliputi kadar besi dan malondialdehid (MDA) hati, aktivitas ALT dan AST plasma, kadar GSH, TNF-α, ekspresi mRNA GPx4 pada hati, serta pemeriksaan histopatologi. Penelitian in-silico dilakukan dengan pendekatan homology modeling dan molecular docking. Hasil penelitian pada tikus menunjukkan bahwa seluruh kelompok terapi belum mampu menurunkan kadar besi hati secara bermakna dibandingkan kelompok KN, tetapi kelompok DPM-2 menunjukkan penurunan kadar besi yang paling baik. Secara histopatologis, terjadi penurunan akumulasi besi yang bermakna pada kelompok DPM-2. Penurunan kadar besi tersebut disertai dengan penurunan kadar MDA, ALT dan AST yang lebih baik dibandingkan monoterapi dengan deferiprone. Terapi kombinasi menyebabkan peningkatan GSH yang tidak bermakna dan belum mampu meningkatkan ekspresi mRNA GPx4. Hasil molecular docking menunjukkan bahwa beberapa senyawa di dalam ekstrak PM dapat berinteraksi dengan transporter DMT-1 dan ZIP-14 dengan binding energy yang cukup baik. Efek inhibisi terhadap transporter harus dibuktikan lebih lanjut secara in-vitro atau in-vivo.

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Iron overload can lead to organ damage through the formation of free radicals and ferroptosis, particularly affecting the liver as the primary iron storage organ. The efficacy of deferiprone, the most commonly used standard chelator in Indonesia for reducing liver iron levels, remains inadequate and poses potential hepatotoxic risks. This study aims to investigate the effects of combining deferiprone with ethanol extract of Phaleria macrocarpa fruit (PM), which has demonstrated iron-chelating properties, in addressing iron overload in a rat model of hemosiderosis. Additionally, the study examines the interaction of active compounds in PM extract with iron uptake transporters (DMT-1 and ZIP-14) through in-silico methods. Rats were divided into six groups: normal (N), negative control (KN), deferiprone (D), combination of standard dose deferiprone and PM extract (DPM1), and combination of half-dose deferiprone and PM extract (DPM2). Iron overload was induced via intraperitoneal injection of iron-dextran for 8 weeks. Therapy commenced from week 4 to week 8. Parameters measured included liver iron and malondialdehyde (MDA) levels, plasma ALT and AST activities, liver GSH levels, TNF-α levels, and mRNA GPx4 expression, and histopathological examination. In-silico studies employed homology modeling and molecular docking approaches. Results indicated that none of the therapy groups significantly reduced liver iron levels compared to the KN group, but the DPM2 group showed the most substantial reduction in iron levels. Histopathological analysis revealed a significant decrease in iron accumulation in the DPM2 group. This iron reduction was accompanied by better reductions in MDA, ALT, and AST levels compared to deferiprone monotherapy. The combination therapy resulted in a non-significant increase in GSH levels and did not enhance mRNA GPx4 expression. Molecular docking results indicated that several compounds in the PM extract could interact with DMT-1 and ZIP-14 transporters with favorable binding energies. To confirm whether these interactions can result in transporter inhibition, further validation through in-vitro or in-vivo studies is necessary."

"Pendahuluan: Akumulasi zat besi berlebih, terutama pada pasien thalassemia yang menerima transfusi darah rutin, dapat memicu penyakit pernapasan seperti PPOK melalui pembentukan radikal bebas. Meskipun kelator besi seperti deferiprone efektif, deferiprone memiliki efek samping seperti neutropenia dan agranulositosis. Phaleria macrocarpa diketahui juga mengandung mangiferin yang bersifat antioksidan dan antiinflamasi. Tujuan penelitian ini untuk mengetahui efektivitas terapi kombinasi deferiprone dan ekstrak etanol P. macrocarpa sebagai alternatif untuk mengobati kondisi kelebihan zat besi dengan efek samping yang lebih rendah. Metode: Penelitian menggunakan tikus Sprague-Dawley (200-250 g) yang dibagi menjadi enam kelompok: Normal (N), Kontrol Negatif (KN), Deferiprone (D), Phaleria macrocarpa (PM), Kombinasi Dosis Penuh (DPM-1), dan Kombinasi Setengah Dosis (DPM-2). Tikus diinjeksi iron dextran 15 mg/x selama 8 minggu. Kelompok perlakuan menerima ekstrak etanol Phaleria macrocarpa (100 mg/kgBB) selama 4 minggu, sedangkan deferiprone diberikan dalam dosis penuh (462,5 mg/kgBB) atau setengah dosis (231,2 mg/kgBB) selama 4 minggu. Kadar zat besi dalam jaringan paru diukur menggunakan Atomic Absorption Spectrometry (AAS). Hasil: Kelompok PM menunjukkan penurunan kadar besi paling rendah di paru dibandingkan KN. Uji normalitas Shapiro-Wilk menunjukkan data terdistribusi normal (p>0,05). Uji One Way Anova tidak menemukan perbedaan signifikan antar kelompok (p>0,05), sehingga uji post hoc tidak dilakukan. Kesimpulan: Pemberian terapi deferiprone dan ekstrak Phaleria macrocarpa secara kombinasi tidak menunjukkan perbedaan yang signifikan dalam penurunan kadar besi di paru secara statistik. Namun, data menunjukkan kadar besi mengalami penurunan walaupun tidak signifkan pada kelompok PM dan DPM2.

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Introduction: Excessive iron accumulation, particularly in thalassemia patients who undergo regular blood transfusions, can lead to respiratory diseases like COPD, through free radical formation. Although iron chelators such as deferiprone are effective, they may cause side effects including neutropenia and agranulocytosis. Phaleria macrocarpa, containing mangiferin, has known antioxidant and anti-inflammatory properties. The study aims to evaluate the effectiveness of combining deferiprone with Phaleria macrocarpa extract for treating iron overload with fewer side effects. Methods: Sprague-Dawley rats (200–250 g) were divided into six groups: Normal (N), Negative Control (KN), Deferiprone (D), Phaleria macrocarpa (PM), Full-Dose Combination (DPM-1), and Half-Dose Combination (DPM-2). The rats were injected with 15 mg/x iron dextran for 8 weeks to induce iron overload. The treatment groups received ethanol extract of Phaleria macrocarpa (100 mg/kg body weight) for 4 weeks, while deferiprone was given at full dose (462.5 mg/kg body weight) or half dose (231.2 mg/kg body weight) for 4 weeks. Iron levels in lung tissues were measured using Atomic Absorption Spectrometry (AAS). Results: The PM group showed the lowest reduction in lung iron levels compared to KN. The Shapiro-Wilk test confirmed that the data were normally distributed (p>0.05). One-way Anova revealed no significant differences between groups (p>0.05), so post hoc tests weren’t conducted. Conclusion: Although the combination of deferiprone and Phaleria macrocarpa extract did not significantly reduce lung iron levels, The data showed that iron levels decreased, although not significantly, in the PM and DPM2 groups."

"Kelebihan besi dapat terjadi akibat transfusi berulang dan peningkatan absorpsi besi pada pasien talasemia. Talasemia dapat menyebabkan splenomegali dan hiperaktivitas limpa, sedangkan kelebihan besi menyebabkan kerusakan DNA dan stress oksidatif. Mangiferin dalam buah Phaleria macrocarpa memiliki potensi sebagai agen pengkelat besi dan antioksidan. Penelitian ini bertujuan untuk menguji ekstrak etanol buah Mahkota Dewa dalam menurunkan kadar besi organ limpa tikus yang mengalami iron overload. Tikus Sprague-Dawley 30 ekor dikelompokkan menjadi normal, kontrol negatif, deferiprone 462,5 mg/kgBB, mangiferin 50 mg/kgBB, Phaleria macrocarpa 100 mg/kgBB (PM1), dan Phaleria macrocarpa 200 mg/kgBB (PM2). Setiap kelompok, kecuali normal, diinjeksikan iron sucrose 15 mg sebanyak 2 kali seminggu secara intraperitoneal. Pada minggu ke-7, dilakukan pengambilan organ limpa untuk dibuatkan homogenat. Homogenat direaksikan dengan HNO3 dan asam perklorat, kemudian ditambahkan aquades dan disaring sebelum kadar besi diukur menggunakan Atomic Absorption Spectrometry (AAS). Kadar besi dimasukkan ke dalam rumus dan dianalisis dengan Kruskall-Wallis. Seluruh kelompok yang diinduksi besi memiliki kadar besi lebih tinggi dibandingkan kelompok normal. Kelompok deferiprone, mangferin, dan PM1 memiliki kadar besi cenderung lebih tinggi daripada kelompok negatif, sedangkan kadar besi PM2 cenderung lebih rendah. Kelompok PM2 menurunkan kadar besi lebih besar daripada PM1, mangiferin, dan deferiprone.

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Iron overload can happen due to repeated transfusion and increased iron absorption in thalassemia patients. Thalassemia can cause splenomegaly and hypersplenism, while iron overload causes DNA’s damage and oxidative stress. Mangiferin from Phaleria macrocarpa’s fruit has potential as iron chelator and antioxidant. This study intends to evaluate ethanol extract of Phaleria macrocarpa’s fruit in reducing iron value in spleen from iron overloaded rats. A total of 30 Sprague-Dawley rats were sorted into normal group, negative control, deferiprone 462,5 mg/kgBW, mangiferin 50 mg/kgBW, Phaleria macrocarpa 100 mg/kgBW (PM1), and Phaleria macrocarpa 200 mg/kgBW (PM2). Every group, except normal, was administered with iron sucrose 15 mg twice a week through intraperitoneal. At week 7th, spleen organs were taken to create homogenates. Homogenates were reacted with HNO3 and perchlorate acid, then added with aquades and filtered before iron levels were measured by Atomic Absorption Spectrometry (AAS). Iron levels were inputted in the formula and analyzed using Kruskall-Wallis. All induced groups have higher iron levels compared to the normal group. Deferiprone, mangiferin, and PM1 tended to have higher iron levels compared to negative control, while iron levels of PM2 tended to be lower. PM2 group reduced iron levels more than PM1, mangiferin, and deferiprone."

"Latar belakang: Besi berlebih dalam tubuh manusia dapat memicu stress oksidatif dan menyebabkan kerusakan ginjal. Malondialdehid (MDA) merupakan produk samping peroksidasi lipid akibat stres oksidatif. Penelitian menunjukkan bahwa senyawa mangiferin yang terkandung dalam buah Phaleria macrocarpa bermanfaat sebagai pengkelat besi. Penelitian ini bertujuan untuk menganalisis efektivitas ekstrak etanol buah Phaleria macrocarpa dalam menurunkan kadar MDA pada ginjal tikus yang diberi besi berlebih. Metode: 30 tikus Sprague-Dawley dibagi dalam 6 kelompok, yaitu normal, kontrol negatif, Deferiprone 462,5 mg/kgBB, Mangiferin 50 mg/kgBB, ekstrak etanol Phaleria macrocarpa 100 mg/kgBB, dan 200 mg/kgBB. Kelompok perlakuan diinjeksikan besi sukrosa intraperitoneal (15 mg/kali) dua kali seminggu selama tiga minggu, dilanjutkan perlakuan sesuai kelompok. Pada minggu ke-7, organ ginjal diambil untuk dibuat homogenat yang selanjutnya diukur kadar proteinnya menggunakan metode Bradford. Kadar MDA diukur dengan Thiobarbituric Acid menggunakan spektrofotometer 530 nm, kemudian hasilnya dibagi kadar protein (nmol/mg protein). Uji statistik yang digunakan berupa perbandingan rerata >2 kelompok menggunakan One-Way ANOVA. Hasil: Semua kelompok induksi besi mengalami peningkatan MDA secara signifikan dibandingkan kelompok tanpa perlakuan. Pemberian mangiferin dan ekstrak etanol Phaleria macrocarpa 100 mg/kgBB berhasil menurunkan kadar MDA secara signifikan dibandingkan kelompok kontrol negatif. Selain itu, dosis 100 mg/kgBB juga memiliki hasil yang paling mendekati nilai normal (3,876 ± 0,248 vs 2,890 ± 0,497). Namun, pemberian dosis 200 mg/kgBB menunjukkan hasil kadar MDA yang paling tinggi (4,868 ± 0,774 nmol/mg protein). Kesimpulan: Pemberian ekstrak etanol buah Phaleria macrocarpa 100 mg/kgBB dapat menurunkan kadar MDA ginjal tikus Sprague-Dawley yang paling baik dibandingkan dosis 200 mg/kgBB maupun kontrol positif.

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Introduction: Iron overload in human body may induce oxidative stress and kidney failure. Malondialdehyde (MDA) is byproduct of oxidative stress induced lipid peroxidation. Studies shown that Mangiferin in Phaleria macrocarpa fruit also useful as chelator agent. This study aims to analyze the effectivity of Phaleria macrocarpa fruits ethanol extract on reducing kidney Malondialdehyde (MDA) levels in rats induced by iron overload. Method: Thirty Sprague-Dawley rats were divided into six groups: normal, negative control, Deferiprone 462.5 mg/kgBW, Mangiferin 50 mg/kgBW, Ethanol extract of Phaleria macrocarpa 100 mg/kgBW, and 200 mg/kgBW. Intervention groups received iron sucrose intraperitoneally (15 mg/times) biweekly for three weeks, followed by corresponding group intervention. At week 7, kidneys were taken to make homogenate. Each sample homogenate was measured its protein using Bradford and MDA level using Thiobarbituric Acid method by spectrophotometer 530 nm (nmol/mg protein). Statistical test used was mean difference among >2 groups using One-Way ANOVA. Result: Iron overload induction groups were associated with significantly higher MDA levels than normal. The administration of mangiferin and ethanol extract 100 mg/kgBW successfully reduced MDA level significantly compared to negative control. Besides, 100 mg/kgBW dose group had the closest MDA to normal (3.876 ± 0.248 vs. 2.890 ± 0.497). However, dose of 200 mg/kgBW showed the highest MDA (4,868 ± 0,774 nmol/mg protein). Conclusion: The administration of 100 mg/kgBW Phaleria macrocarpa fruits ethanol extract was associated with the best reduction of kidney MDA level in Sprague-Dawley rats induced by iron overload compared to either 200 mg/kgBW dose or positive control."

"Latar Belakang: Phaleria macrocarpa (PM) mengandung mangiferin yang memiliki kemampuan sebagai kelator besi dengan membentuk kompleks. Kompleks dapat menekan akumulasi besi pada pasien talasemia yang rutin transfusi. Kondisi besi berlebih dapat mempengaruhi terjadinya cedera organ ginjal. Penelitian bertujuan untuk mengetahui efektivitas ekstrak etanol buah PM sebagai agen kelator besi diamati pada organ ginjal tikus model besi berlebih. Metode: 30 tikus Sprague-Dawley dibagi acak 6 kelompok: normal (N), besi berlebih (KN), besi berlebih diobati Deferiprone dosis 462,5 mg/kgBB (D), besi berlebih diobati mangiferin dosis 50mg /kgBB (M), besi berlebih diobati ekstrak PM dosis 100mg/kgBB (PM100), besi berlebih diobati ekstrak PM dosis 200mg/kgBB (PM200). Injeksi besi diberikan 2kali/minggu selama 3 minggu dilanjutkan 8 minggu bersama pengobatan. Kadar besi ginjal diukur menggunakan AAS. Kadar urea dan kreatinin plasma serta TNF-α ginjal diukur menggunakan kit. Hasil: Mangiferin dari ekstrak terdeteksi pada ginjal tikus model besi berlebih diukur dengan HPLC. Mangiferin dan PM tidak dapat menurunkan kadar besi di organ ginjal dan kadar ureum plasma signifikan. Pengaruh mangiferin dan PM pada kadar kreatinin plasma tidak linier. Mangiferin dan PM dapat menurunkan kadar TNF-α ginjal signifikan dengan KN dan D.Kesimpulan: Mangiferin dan PM memiliki potensi kelator besi dan menurunkan respon inflamasi pada kondisi besi berlebih.

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Background: Mangiferin, active compound in Phaleria macrocarpa (PM), has been shown as an iron chelating agent by forming complexes. The complex can reduce iron accumulation in thalassemia patients receive transfusions. Renal organ failure can be impacted by the high iron. This study aims to determine the effectiveness of ethanolic extract of PM fruit as iron chelating agent observed in the kidney of iron overload rat.

Methods: 30 Sprague-Dawley divided randomly six groups: normal (N), iron-overload (KN), iron-overload treated Deferiprone dosage 462,5 mg/kgBW (D), iron-overload treated mangiferin dosage 50mg/kgBW (M), iron-overload treated PM extract dosage 100mg/kgBW (PM100) and iron-overload treated with PM extract dosage 200mg/kgBW (PM200). Iron injection was administered twice/week for 3 weeks, continued 8 weeks with treatment. Kidney iron levels of rats measured using AAS. Plasma urea and creatinine levels as well as renal TNF-α measured using kit.

Results: Mangiferin from extract was detected in the kidney of rat iron overload models which measured using HPLC. Mangiferin and PM cannot significantly reduce plasma urea and kidney iron levels. Effect of mangiferin and PM on plasma creatinine levels not linearly. Mangiferin and PM can reduce renal TNF-α levels significantly.

Conclusion: Mangiferin and PM have ability as iron chelator and reduce inflammatory response caused iron overload."

"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.

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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."

"Latar Belakang Besi berlebih dapat meningkatkan stress oksidatif dan merusak jantung. Salah satu marker yang digunakan dalam mendeteksi stress oksidatif adalah malondialdehid (MDA). Buah Phaleria macrocarpa L mengandung mangiferin yang bermanfaat sebagai kelator besi. Penelitian ini bertujuan untuk menganalisis efektivitas ekstrak etanol buah Phaleria macrocarpa L dalam menurunkan kadar MDA pada jantung tikus yang diberi besi berlebih. Metode 30 tikus Sprague-Dawley dibagi ke dalam 6 kelompok, yaitu kelompok normal, kontrol negatif, deferiprone 462,5mg/kgBB, mangiferin 50mg/kgBB, ekstrak etanol buah Phaleria macrocarpa L 100mg/kgBB dan 200mg/kgBB. Setiap kelompok perlakuan kecuali kelompok normal diberi besi intraperitoneal sebanyak 3x/minggu, dosis 15mg/kali selama 8 minggu. Terapi diberikan mulai minggu ke 4, pada minggu ke-8, jantung diambil, dijadikan homogenat untuk pengukuran kadar MDA menggunakan spektrofotometer. Analisis statistic menggunakan Kruskal-Wallis. Hasil Kontrol negatif mengalami peningkatan kadar MDA yang signifikan dibandingkan kelompok normal. Pemberian ekstrak etanol buah Phaleria macrocarpa L 100mg/kgBB dan 200mg/kgBB berhasil menurunkan kadar MDA dibandingkan dengan kontrol negatif. Kadar MDA dosis 100mg/kgBB (0,06±0,02nmol/mg organ) dan dosis 200mg/kgBB (0,13±0,01nmol/mg organ), lebih rendah dibandingkan dengan kontrol negatif (0,22±0,05nmol/mg organ). Kesimpulan Pemberian ekstrak etanol buah Phaleria macrocarpa L 100mg/kgBB dan 200 mg/kgBB dapat menurunkan kadar MDA organ jantung tikus Sprague-Dawley.

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Introduction Iron overload can increase oxidative stress and cause heart failures. One of the markers used in detecting oxidative stress is malondialdehyde (MDA). Phaleria macrocarpa L fruit contains mangiferin which is useful as iron chelator. This study aims to analyze the effectiveness of ethanol extract of Phaleria macrocarpa L fruit in reducing MDA levels in heart of rats induced by iron overload. Method 30 Sprague-Dawley rats were divided into 6 groups, namely normal group, negative control, deferiprone 462,5mg/kgBW, mangiferin 50mg/kgBW, ethanol extract of Phaleria macrocarpa L 100mg/kgBW and 200mg/kgBW. Each treatment group other was given intraperitoneal iron injections 3 times/week, 15mg/time for 8 weeks. At week- 8, heart was taken to be used as homogenate and followed by measuring protein levels using Bradfort test. MDA levels were measured with TBA solution using 530nm spectrophotometer, then absorbance results were divided by the protein levels of the heart. Then analysis was carried out using Kruskal-Wallis. Results The negative control group experienced significant increase in MDA levels compared to the normal group. Administration of extract ethanol of Phaleria macrocarpa L fruit 100mg/kgBW and 200mg/kgBW was successful in reducing MDA levels compared to the negative control. MDA level in dose of 100mg/kgBW (0.06±0.02nmol/mg organ), 200mg/kgBW (0.13±0.01nmol/mg organ), lower than the negative control (0.22±0.05nmol/mg organ). Conclusion Administration of ethanol extract of Phaleria macrocarpa L fruit 100mg/kgBW can reduce MDA levels in the heart organs of Sprague-Dawley rats."

"Iron overload adalah kondisi besi berlebih yang disebabkan oleh transfusi darah berkepanjangan. Iron overload dapat menyebabkan terbentuknya radikal bebas dan stres oksidatif, sehingga dapat menyebabkan kerusakan jaringan pada organ paru. Buah mahkota dewa yang mengandung mangiferin, diketahui berpotensi menjadi agen pengkelat besi. Penelitian ini bertujuan untuk mengetahui efek ekstrak buah mahkota dewa sebagai agen pengkelat besi pada organ paru-paru tikus dengan kelebihan besi. Tikus Sprague-dawley jantan akan dibagi menjadi 6 kelompok, kelompok normal, kontrol negatif, deferipron 462,5 mg/kgBB, mangiferin 50 mg/kgBB, Phaleria macrocarpa 100 mg/kgBB, dan Phaleria macrocarpa 200 mg/kgBB. Iron sucrose diberikan kepada semua kelompok kecuali kelompok normal sebanyak 15 mg sebanyak 2 kali seminggu secara intraperitoneal hingga minggu ke-7, kemudian dilarutkan dalam larutan asam perklorat, larutan HNO3, dan aquades. Hasil yang didapatkan adalah semua kelompok yang diinduksi besi, kecuali Phaleria macrocarpa 200 mg/kgBB cenderung menurunkan kadar besi, meskipun tidak signifikan. Kadar besi pada kelompok PM 1 lebih rendah dari kelompok deferipron dan mangiferin, sedangkan kelompok PM2 lebih tinggi dari kelompok kontrol negatif. Kelompok PM1 menurunkan kadar besi lebih baik dibandingkan PM2, mangiferin, dan deferipron

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Iron overload is a condition of excess iron caused by prolonged blood transfusions. Iron overload can cause the formation of free radicals and oxidative stress, which can cause tissue damage to the lungs. Mahkota dewa which contains mangiferin, is known to have the potential to be an iron chelating agent. This study aims to determine the effect of Mahkota Dewa fruit extract as an iron chelating agent in the lungs of rats with excess iron. Male Sprague-Dawley rats will be divided into 6 groups, normal group, negative control, deferipron 462.5 mg/kgBB, mangiferin 50 mg/kgBB, Phaleria macrocarpa 100 mg/kgBB, and Phaleria macrocarpa 200 mg/kgBB. Iron sucrose was given to all groups except the normal group as much as 15 mg 2 times a week intraperitoneally until the 7th week, then dissolved in perchloric acid solution, HNO3 solution, and distilled water. The results obtained were that all groups induced by iron, except Phaleria macrocarpa 200 mg/kg, tended to decrease iron levels, although not significantly. Iron levels in the PM1 group were lower than the deferipron and mangiferin groups, while the PM2 group was higher than the negative control group. The PM1 group reduced iron levels better than PM2, mangiferin, and deferipron"

"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."

"ABSTRAKLatar Belakang: Muatan besi berlebih akibat transfusi darah dan peningkatan serapan besi di saluran cerna, masih merupakan isu penting pada Thalasemia Intermedia TI , dan dikaitkan dengan berbagai komplikasi yang meningkatkan morbiditas dan mortalitas. Pemeriksaan MRI T2 hati sebagai pemeriksaaan yang tervalidasi dalam menilai Liver Iron Concentration LIC , merupakan pemeriksaan yang mahal dan tidak tersedia secara merata di Indonesia.Tujuan: Mengetahui gambaran muatan besi berlebih darah dan hati pada pasien thalasemia intermedia dewasa dan korelasi antara saturasi transferin, feritin serum, MRI T2 hati, dan LIC yang dinilai dengan pemeriksaan MRI T2 hati dengan nilai elastografi hati.Metode: Penelitian potong lintang pada pasien thalasemia intermedia dewasa dengan transfusi darah dan dengan atau tanpa kelasi besi di RSUPNCM dr. Cipto Mangunkusumo mulai dari bulan Agustus sampai dengan Oktober 2016, dengan total subyek penelitian sebanyak 45 orang. Dilakukan pemeriksaan saturasi transferin, feritin serum, elastografi hati, dan MRI T2 hati. Analisis statistik menggunakan uji korelasi Pearson dan Spearman.Hasil: Sebanyak 64,4 subyek penelitian adalah Thalasemia ?-Hb E, dengan median RIK umur 33 22 tahun. Sebanyak 84,4 subyek penelitian mendapatkan transfusi darah secara reguler. Seluruh subyek penelitian mengalami komplikasi hemosiderosis hati melalui pemeriksaan MRI T2 hati. Sebanyak 48,9 mengalami hemosiderosis hati berat, dengan nilai median MRI T2 hati 1,6 ms. rerata feritin serum adalah 2831 1828 ng/mL, dengan nilai median saturasi transferin 66 . Nilai rerata LIC melalui pemeriksaan MRI T2 adalah 15,36 7,37 mg besi/gr berat kering hati dan nilai rerata elastografi hati adalah 7,7 3,8 Kpa. Uji korelasi didaptakan terdapat korelasi nilai elastografi hati dan rerata feritin serum r = 0,651; p = 0,000 , nilai elastografi hati dan LIC r = 0,433; p = 0,003 dan korelasi negatif nilai elastografi hati dan MRI T2 hati r = -0,357; p = 0,016 .Simpulan: Terdapat korelasi antara muatan besi berlebih feritin serum dan LIC dengan nilai elastografi hati. Terdapat korelasi negatif nilai elastografi hati dengan MRI T2 hati pada pasien thalasemia intermedia dewasa.

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ABSTRACTBackground Iron overload is a common feature of thalassemia intermedia due to regular blood transfusion and increase gastrointestinal iron absorption. Early detection and adequate iron chelator can significantly decrease related morbidities and mortality due to complication from iron overload. Liver Iron Concentration LIC is the best way to measure body iron stores. MRI T2 as a validated test to identify LIC, is expensive and currently not available in all medical services in Indonesia.Objective To identify liver iron overload and correlation of transferrin saturation, serum ferritin, liver MRI T2 , and LIC with transient liver elastography in adult thalassemia intermedia patient.Methods We conducted a cross sectional study enrolling 45 patients with thalassemia intermedia with blood transfusion and with and without iron chelator therapy. The study was conducted at Cipto Mangunkusumo Hospital from August 2016 through October 2016. We performed measurements of transferrin saturation, serum ferritin level, transient liver elastography and liver MRI T2 . The Pearson and Spearman correlation test were used to evaluate the correlation transient liver elastography with transferrin saturation, serum ferritin, Liver MRI T2 , and LIC.Results As much as 64,4 of study subject are Hb E Thalasemia Intermedia with median IQR age is 33 22 years old. As much as 84,4 of study subject have regular blood transfusion. On the basis of liver MRI T2 , all studi subject suffered from liver iron overload, with 48,9 had severe liver iron overload. The median value of Liver MRI T2 was 1,6 ms. The mean serum ferritin was 2831 1828 ng mL, with median value of transferrin saturation was 66 . The mean of LIC corresponding to Liver MRI T2 and mean liver stiffness measurement was 15,36 7,37 mg Fe gr dry weight and 7,7 3,8 Kpa respectively. Liver Stiffness correlated with serum ferritin r 0,651 p 0,000 , Liver MRI T2 r 0,357 p 0,016 , and LIC r 0,433 p 0,003 . No correlation was found between liver elastography and transferrin saturation r 0,204 p 0,178 .Conclusions Serum ferritin, Liver MRI T2 , and LIC correlated with liver elastography. No correlation was found between transferin saturation and liver elastography. "