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Expression of hypoxia inducible factor-1α (HIF-1α) gene and apoptosis in the heart induced by systemic hypoxia Hendrawan, Siufui; Jusman, Sri W.A.; Ferdinal, Frans; Prijanti, Ani R.; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 18, No 2 (2009): April-June
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Aim This study explored the expression of HIF-1α in hypoxic cardiac muscle in mice, and observed the evidence of apoptosis in hypoxia induced cardiomyocyte.Methods Male Sprague-Dawley rats, were randomized into 7 groups (n = 4 per group): control normoxia group that was exposed to atmospheric oxygen and hypoxia groups that were housed in hypoxic chambers (O2 level 8%) for 1, 3, 7, 14, 21, and 28 days respectively. Animals were sacrificed, hearts were rapidly excised, total RNA was extracted with an mRNA isolation kit and the expression of HIF-1α mRNA was then detected by real-time RT-PCR. Apoptosis was assessed by TUNEL method.Results For rat in hypoxia group, the expression of HIF-1α mRNA in cardiac myocytes was clearly up-regulated compared to the control normoxia group. Further, HIF-1α expression level elevated gradually and reached a peak at 21 days of hypoxia. No cell labeled by the TUNEL method was detected in the control group. Compared with the control group, the apoptotic index was significantly increased in the hypoxia group (P < 0.05). There was no significant correlation between the elevation of HIF-1α mRNA and the elevation of apoptotic index.Conclusion Systemic chronic hypoxia caused the elevation of HIF-1α mRNA and apoptosis in cardiac myocytes. (Med J Indones 2009; 18: 97-101)Keywords: TUNEL, RT-PCR, mRNA, apoptotic index
Myocardial damage after continuous aerobic and anaerobic exercise in rats Flora, Rostika; Ferdinal, Frans; Hernowo, Bethy S.; Wanandi, Septelia I.; Sadikin, Mohamad; Freisleben, Hans-Joachim
Medical Journal of Indonesia Vol 22, No 4 (2013): November
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Background: Regular physical activity is highly recommended in preventive, curative, and rehabilitative programs in order to promote health, especially cardiovascular health. However, physical activity can also cause sudden death. In athletes, sudden death may occur during sport competitions, with myocardial infarction as the most common etiology. It is suspected that continuous training without any rest-day play a role in cardiac muscle damage and sudden death during competition. Our study was aimed to learn about cardiac muscle adaptation on continuous aerobic and anaerobic physical activity without any rest-day. Methods: The specimens in our study were cardiac muscle tissue obtained from rats that had performed aerobic and anaerobic physical activity on treadmill for 1, 3, 7, and 10 days without any rest-day. Blood gas analysis and hematological assessment were used as parameters of systemic adaptation to hypoxia during physical activity. Moreover, histopathology of cardiac muscle tissue was performed as parameter for cardiac muscle damage.Results: The results showed that aerobic and anaerobic physical activity caused a systemic hypoxic condition and triggered adaptation responses. Cardiac muscle damage occurred on the 10th day in both treatment groups, with more severe damage observed in the group with anaerobic physical activity. The tissue protein level in the anaerobic group increased progressively on the 10th day.Conclusion: Physical activity may result in hypoxia and systemic adaptation. Aerobic and anaerobic physical activities performed for 10 days without any rest-day may cause cardiac muscle damage. (Med J Indones. 2013;22:209-14. doi: 10.13181/mji.v22i4.601)Keywords: Cardiac muscle, cardiac muscle damage, histopathology, physical activity
Cytoglobin expression in oxidative stressed liver during systemic chronic normobaric hypoxia and relation with HIF-1α Jusman, Sri W.A.; Iswanti, Febriana C.; Suyatna, Franciscus D.; Ferdinal, Frans; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 23, No 3 (2014): August
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Background: Liver is sensitive against hypoxia and hypoxia will stabilize HIF-1α. At the same time, hypoxia will produce reactive oxygen species (ROS) which can be scavenged by Cygb. The purpose of our study is to know, if normobaric hypoxia can induce Cygb expression and its association with HIF-1α stabilization.Methods: This is an experimental study using 28 male Sprague-Dawley rats, 150-200 g weight. Rats are divided into 7 groups: control group and treatment groups that are kept in hypoxic chamber (10% O2: 90% N2) for 6 hours, 1, 2, 3, 7 and 14 days. All rats are euthanized after treatment and liver tissue are isolated, homogenized and analyzed for oxidative stress parameter, expression of Cygb and HIF-1α.Results: Expression of Cygb mRNA and protein was increased on the day-1 after treatment and reach the maximum expression on the day-2 of hypoxia treatment. But, the expression was decreased after the day-3 and slightly increased at the day-14 of hypoxia. The correlation between expression of Cygb and oxidative stress parameter was strongly correlated. Cygb mRNA, as well as protein, showed the same kinetic as the HIF-1, all increased about day-1 and day-2.Conclusion: Systemic chronic hypoxia and/or oxidative stress up-regulated HIF-1α mRNA which is correlated with the Cygb mRNA and protein expression. Cygb mRNA as well as Cygb protein showed the same kinetic as the HIF-1, all increased about day-1 and day-2 suggesting that Cygb could be under the regulation of HIF-1, but could be controlled also by other factor than HIF-1.
Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise Flora, Rostika; Freisleben, Hans-Joachim; Ferdinal, Frans; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 21, No 3 (2012): August
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α). The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium.Results: Both, HIF-1α protein and VEGF were increased (p < 0.05) in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66). Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35), while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73). The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59) in the aerobic group and strong in the anaerobic group (r = 0.69).Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise. (Med J Indones. 2012;21:133-40)Keywords: Exercise, HIF-1α, myocardium, VEGF
Expression of Hypoxia-Inducible Factor-1α and Myoglobin in Rat Heart as Adaptive Response to Intermittent Hypobaric Hypoxia Exposure Herawati, Margaretha; Wardaya, .; Mulyawan, Wawan; Farhan, Fanny Septiani; Ferdinal, Frans; Jusman, Sri Widia A.; Sadikin, Mohamad
HAYATI Journal of Biosciences Vol 24, No 3 (2017): July 2017
Publisher : Bogor Agricultural University, Indonesia

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Abstract

The aim of this study was to investigate the influence of intermittent hypobaric hypoxia on the expression hypoxia adaptation proteins, namely hypoxia inducibla factor-1a (HIF-1a) and myoglobin (Mb). Twenty five male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia in a hypobaric chamber in Indonesian Air Force Institute of Aviation Medicine, for 49.5 minutes at various low pressure, 1 week interval for 4 times (day 1, 8, 15 and 22). HIF-1α and Mb protein were measured with ELISA. mRNA expression of Mb was measured with one step real time RT-PCR. HIF-1α protein levels increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p = 0.0437). mRNA expression and protein of Mb increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p = 0.0283; 0.0170), and both are strongly correlated (Pearson, r = 0.6307). The heart of rats adapted to intermittent hypoxia conditions by upregulation the expression of HIF-1a and myoglobin and then both return to normal level.
THE EFFECT OF MAJA FRUIT [Aegle marmelos (L) Correa] ON INFLAMMATION MARKERS INVOLVED IN THE AGING PROCESS Limanan, David; Christian, NO; Efrany, E; Yulianti, E; Ferdinal, Frans
Acta Biochimica Indonesiana Vol 1, No 1 (2018): ACTA BIOCHIMICA INDONESIANA
Publisher : PP PBBMI

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Abstract

Background: Aging is a process that every living creature will pass through and involves various factors. Increased inflammatory factors can be caused by hypoxia which forms Reactive Oxygen Species (ROS) and damages macromolecules and causes the acceleration of the aging process. Maja plants, empirically have long been used as medicinal plants, research on Maja leaves shows anti-inflammatory and antioxidant potential.Objective: The purpose of this study was to find out and understand the potential of Maja fruit in the presence of inflammatory markers of IL-6 and TNF-α which are involved in the aging process.Methods: This research was in vivo experimental, using male experimental animals Sprague Dawley rats divided into 8 groups (n = 4), and divided into 2 groups (fed with Maja ethanol extract (400 mg/ kg/day, 14 days) and not force-fed). Each group was divided into 4 subgroups (normoxia, hypoxia (O2 8%, N2 92%) for 3, 7 and 14 days). At the end of the trial period, animal blood was examined for IL-6 and TNF-α concentrations using the ELISA method.Results: The results showed an increase in levels of IL-6 and TNF-α both in the group fed and not fed in line with the duration of hypoxia when compared with controls. However, groups that are not force-fed show a higher pattern compared to those who are force-fed.Conclusion : The ethanol extract of Maja fruit can help slow down the aging process.
EXPRESSION OF APELIN IS RELATED TO OXIDATIVE DAMAGE IN HEART TISSUE OF RATS DURING CHRONIC SYSTEMIC HYPOXIA Helmi, H R; Ferdinal, Frans; Prijanti, Ani Retno; Jusman, Sri Widia A; Suyatna, Frans D
Acta Biochimica Indonesiana Vol 1, No 2 (2018): ACTA BIOCHIMICA INDONESIANA
Publisher : PP PBBMI

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Abstract

Background: Chronic systemic hypoxia is severe environmental stress for the heart and might lead to the development of heart failure. Apelin is an endogenous peptide that has been shown to have various beneficial effects on cardiac function. Apelin appears to have a role to play in the ventricular dysfunction and maintaining the performance of the heart.Objectives: In the present study we want to investigate the adaptive response of heart tissue to chronic systemic hypoxia and the correlation with apelin expression and oxidative stress in rat. Methods: An experimental study was performed using 28 Sprague-Dawley male rats, 8 weeks of age. Rats were divided into 7 groups 4 each, namely control group; normoxia (O2 atmosphere) and the treatment group of hypoxia (8% O2) for 6 hours; 1;3;5;7 and 14 days respectively. Body weight and heart weight were measured at each treatment. Ventricular thickness was measured by caliper, Apelin mRNA was measured using real-time qRT-PCR with Livak formula and malondialdehyde (MDA) level was used to assess oxidative stress due to cardiac tissue hypoxia.Results: Macroscopic exams showed hypertrophy at day 7th. The relative expression of Apelin mRNA in hypoxic heart is decreased at the beginning and then increased, starting from day-7 to day-14. The MDA levels were significantly increased from day-7 and were strongly correlated with relative expression Apelin.Conclusion:  It is concluded that the increase of Apelin expression is related to oxidative stress in heart tissue of rats during chronic systemic hypoxia.
Kapasitas Total Antioksidan dan Sitotoksisitas Ekstrak Metanol Daun Ara (Ficus auriculata Lour) Limanan, David; Ferdinal, Frans; Salim, Melanie; Julianty, Eny
Jurnal Muara Sains, Teknologi, Kedokteran dan Ilmu Kesehatan Vol 2, No 1 (2018): Jurnal Sains, Teknologi, Kedokteran dan Ilmu Kesehatan
Publisher : Direktorat Penelitian dan Pengabdian kepada Masyarakat, Universitas Tarumanagara

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Abstract

Indonesia merupakan negara megabiodiversitas paling tinggi di dunia. Keragaman flora Indonesia menduduki peringkat ketujuh dunia Hal ini membuat Indonesia memiliki kandidat tanaman obat yang luas, akan tetapi hanya sebagian kecil yang telah dimanfaatkan sebagai bahan baku industri obat. Salah satu tanaman yang memiliki khasiat obat dan telah digunakan secara empirik adalah tanaman ara (Ficus auriculata Lour). Tanaman ara diketahui memiliki senyawa bioaktif yang dapat berfungsi sebagai antioksidan dan dapat digunakan untuk mengatasi stres oksidatif yang merupakan dasar dari berbagai macam penyakit, salah satunya adalah kanker. Selain itu obat-obatan kanker menimbulkan efek samping yang besar terhadap sel-sel normal, sehingga diperlukan penelitian lebih lanjut dalam mencari kandidat antikanker yang cukup efektif dengan efek samping kecil. Bahan bioaktif dari tanaman banyak yang cukup menjanjikan sebagai kandidat obat anti kanker. Karena itu, penelitian ini dilakukan untuk melihat kapasitas total antioksidan dan sifat sitotoksisitas dari ekstrak daun ara. Metode pada penelitian ini berupa penelitian eksperimantal, dengan daun ara yang telah didapatkan dibuat simplisia dan diekstraksi dengan metode maserasi menggunakan pelarut metanol. Hasil ekstraksi dilakukan pengujian kapasitass total antioksidan dengan menggunakan DPPH (Blois) dan uji sitotoksisitas menggunakan metode Brine Shrimp Lethality Test (BSLT).Hasil penelitian didapatkan bahwa kapasitas total antioksidan ekstrak metanol daun ara diperoleh sebesar 213,2564 µg/mL, sedangkan IC-50 asam askorbat sebagai kontrol sebesar 5,9382 µg/mL. Uji sitotoksisitas ekstrak metanol daun ara didapatkan LC50 sebesar 448,895 ppm. Dari hasil penelitian dapat disimpulkan bahwa ekstrak metanol daun ara memiliki kapasitas antioksidan yang lebih kecil dibanding vitamin c tetapi memiliki bersifat sitotoksik sehingga dapat dijadikan kandidat antikanker.Kata Kunci : Ara, sitotoksisitas, kapasitas antioksidan