Skripsi

Pengaruh Pemberian Kombinasi Deferiprone dan Ekstrak Etanol Buah Mahkota Dewa Terhadap Ekspresi Gen DMT1 pada Organ Hati Tikus Model Hemosiderosis = The Effect of the Combination of Deferiprone and Ethanol Extract of Mahkota Dewa Fruit on DMT1 Gene Expression in the Liver of Hemosiderosis Model Rats.

Latar Belakang Iron overload merupakan akumulasi sistemik zat besi, salah satunya akibat transfusi darah yang berkepanjangan. Iron overload dapat memicu hemosiderosis pada organ hati yang difasilitasi oleh DMT1. Hemosiderosis ditatalaksana dengan kelasi besi standar seperti Deferiprone yang memiliki biaya tinggi dan risiko toksisitas berupa agranulosis serta kegagalan organ. Di sisi lain, Phaleria macrocarpa mengandung mangiferin yang berpotensi sebagai agen kelator alternatif. Oleh karena itu, penelitian ini bertujuan untuk menganalisis pengaruh kombinasi Deferiprone dan ekstrak Phaleria macrocarpa terhadap ekspresi gen DMT1 pada hati tikus model hemosiderosis. Metode Sebanyak 29 tikus Sprague-Dawley dibagi menjadi enam kelompok: normal (N), hemosiderosis (KN), Deferiprone 462,5 mg/kgBB (D), ekstrak Phaleria macrocarpa 100 mg/kgBB (PM), dan dua kelompok kombinasi (DPM1: full dose (462,5 mg/kgBB); DPM2: half dose (231,25 mg/kgBB) Deferiprone). Hemosiderosis diinduksi dengan injeksi iron sucrose 15 mg secara intraperitoneal. Setelah periode perlakuan, mRNA DMT1 diisolasi dari organ hati dan ekspresinya dikuantifikasi menggunakan qRT-PCR dengan gen pembanding β-Aktin. Data dianalisis secara statistik menggunakan SPSS 25. Hasil Tidak ada perbedaan bermakna pada ekspresi DMT1 antar kelompok perlakuan. Ekspresi DMT1 terendah ditunjukkan pada kelompok KN, sedangkan ekspresi tertinggi ditemukan pada kelompok kombinasi dosis penuh (DPM1). Semua kelompok terapi (D, PM, DPM1, dan DPM2) menunjukkan peningkatan ekspresi DMT1 dibandingkan kelompok KN. Peningkatan ekspresi pada kelompok kombinasi lebih tinggi daripada terapi tunggal. Kesimpulan Kombinasi Deferiprone dan ekstrak Phaleria macrocarpa secara sinergis meningkatkan ekspresi gen DMT1 lebih kuat dibandingkan terapi tunggal. Efek upregulasi ini kemungkinan bersifat dose-dependent, yaitu dosis Deferiprone yang lebih banyak menunjukkan peningkatan ekspresi DMT1 yang cenderung lebih tinggi.
Kata Kunci: DMT1, Deferiprone, Phaleria macrocarpa, Hemosiderosis, Kelasi Besi


Background Iron overload is the systemic accumulation of iron, one of which is the result of prolonged blood transfusions. Iron overload can trigger hemosiderosis in the liver, facilitated by DMT1. Hemosiderosis is managed with standard iron chelators such as Deferiprone, which are expensive and carry the risk of toxicity in the form of agranulosis and organ failure. On the other hand, Phaleria macrocarpa, which contains mangiferin, has the potential as an alternative chelating agent. Therefore, this study aimed to analyze the effect of a combination of Deferiprone and Phaleria macrocarpa extract on DMT1 gene expression in the livers of hemosiderosis model rats. Methods Twenty-nine Sprague-Dawley rats were divided into six groups: normal (N), hemosiderosis (KN), Deferiprone 462.5 mg/kgBW (D), Phaleria macrocarpa extract 100 mg/kgBW (PM), and two combination groups (DPM1: full dose (462.5 mg/kgBW); DPM2: half dose (231.25 mg/kgBW) of Deferiprone). Hemosiderosis was induced by intraperitoneal injection of 15 mg of iron sucrose. After the treatment period, DMT1 mRNA was isolated from the liver and its expression was quantified using qRT-PCR with the reference gene β-Actin. Data were statistically analyzed using SPSS 25. Results There was no significant difference in DMT1 expression between treatment groups. The lowest DMT1 expression was found in the KN group, while the highest expression was found in the full-dose combination group (DPM1). All treatment groups (D, PM, DPM1, and DPM2) showed increased DMT1 expression compared to the KN group. The increase in expression in the combination group was higher than in the single therapy group. Conclusion The combination of Deferiprone and Phaleria macrocarpa extract synergistically increased DMT1 gene expression more strongly than either therapy alone. This upregulation effect is likely dose-dependent, with higher doses of Deferiprone showing a tendency for higher DMT1 expression increases.
Keywords: DMT1, Deferiprone, Phaleria macrocarpa, Hemosiderosis, Iron chelation