Tesis

Efek Kombinasi Deferipron dengan Ekstrak Etanol Buah Phaleria Macrocarpa L. dalam Mencegah Kardiomiopati Pada Tikus Model Hemosiderosis = The Effect of Administering a Combination of Deferiprone and Ethanol Extract of Phaleria macrocarpa L. Fruit in Preventing Cardiomyopathy in a Hemosiderosis Rat Model.

Deposisi kelebihan besi yang belum merusak jaringan disebut sebagai hemosiderosis. Keadaan ini terjadi pada pasien thalasemia yang diberikan transfusi darah berulang. Iron overload memicu peningkatan non-transferrinbound iron (NTBI) dan Reactive oxygen species (ROS) yang berujung pada kardiomiopati. Deferipron adalah kelasi besi standar memiliki efek samping agranulositosis. Buah Phaleria macrocarpa (PM) mengandung senyawa mangiferin yang mampu mengkelat besi. Penelitian ini menggunakan tikus Sprague dawley jantan yang diberikan induksi iron dextran 2 kali/minggu dengan dosis 15mg/IP selama 3 minggu untuk pemodelan tikus hemosiderosis yang mengalami kardiomiopati. Pemberian terapi dilakukan dalam beberapa kelompok yaitu kelompok Deferipron dosis 462,5mg/kgBB, ekstrak etanol PM 100mg/kgBB, kombinasi deferipron dosis 462,5mg/kgBB dan ekstrak etanol PM (DPM1) dan kombinasi deferipron dosis 231,25mg/kgBB dan ekstrak etanol PM (DPM2) sambil dilanjutkan induksi selama 5 minggu. Pemberian induksi iron dextran mampu meningkatkan kadar BNP plasma sebagai indikator terjadinya kardiomiopati. Perlakuan kombinasi deferipron setengah dosis dan ekstrak etanol Phaleria macrocarpa (DPM2) mampu menurunkan kadar besi jantung, ferritin plasma, MDA jantung, dan BNP plasma secara signifikan (p < 0,05). Perlakuan DPM2 dapat menurunkan ekspresi gen senescence SUR2A, sedangkan gen senescence p21 belum dapat diturunkan secara signifikan, dan gen p16 tidak didapatkan ekspresi pada pemeriksaan. Perlakuan DPM2 memiliki ketebalan ventrikel kiri yang lebih tipis dibandingkan kelompok kontrol dengan nilai signifikan (p < 0,05) menunjukkan adanya proses pencegahan terjadinya hipertropi kardiomiopati.
Kata kunci: Hemosiderosis, Ekstrak Buah Mahkota Dewa, Deferiprone, Kardiomiopati


Deposition of excess iron that has not damaged tissue is referred to as hemosiderosis. This situation occurs in thalassemia patients who are given repeated blood transfusions. Iron overload triggers an increase in non-transferrinbound iron (NTBI) and reactive oxygen species (ROS) which leads to cardiomyopathy. Deferiprone is a standard iron chelator that has the side effect of agranulocytosis. Phaleria macrocarpa (PM) fruit contains the compound mangiferin which is able to chelate iron. This study used male Sprague Dawley rats that were given iron dextran induction 2 times/week at a dose of 15 mg/IP for 3 weeks to model hemosiderosis rats that experience cardiomyopathy. The therapy was given in several groups, namely the Deferiprone group with a dose of 462.5mg/kgBW, ethanol extract PM 100mg/kgBW, a combination of deferipron dose 462.5mg/kgBW and ethanol extract PM (DPM1) and a combination of deferiprone dose 231.25mg/kgBW and ethanol extract PM (DPM2) while continuing induction for 5 weeks. Induction administration of iron dextran can increase plasma BNP levels as an indicator of cardiomyopathy. The combination treatment of half dose deferiprone and ethanol extract of Phaleria macrocarpa (DPM2) was able to reduce heart iron, plasma ferritin, heart MDA and plasma BNP levels significantly (p < 0.05). DPM2 treatment could reduce the expression of the senescence gene SUR2A, while the senescence gene p21 could not be reduced significantly, and the gene p16 was not found to be expressed in the examination. The DPM2 treatment had a thinner left ventricular thickness than the control group with a significant value (p < 0.05) indicating the process of preventing hypertrophic cardiomyopathy.
Keywords: Hemosiderosis, Mahkota Dewa Fruit Extract, Deferiprone, Cardiomyopathy