Kahdar Wiradisastra
Departemen Bedah Saraf Fakultas Kedokteran Universitas Padjadjaran-Rumah Sakit Dr. Hasan Sadikin Bandung

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Decreased Oxidative Stress and Apoptosis post Intermittent Hypobaric Hypoxia Exposures in Sprague Dawley Male Mice Cardiac Cells Hidayat, Achmad; Wiradisastra, Kahdar; Hernowo, Bethy Setiawaty; Achmad, Tri Hanggono
Journal of the Indonesian Medical Association Vol. 61 No. 7 July 2011
Publisher : Journal of the Indonesian Medical Association

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Abstract

Aviators often experience intermittent hypobaric hypoxia (IHH) which may cause apoptosis. This study was aimed to analyze the effects of IHH on oxidative stress and apoptosis. Experimental study conducted in February-April 2010 consisted of one control group and four exposed groups of male mice Sprague Dawley. Each group consisted of 7 mice. The control group did not have IHH. The exposed groups (with an interval of one week) had once, twice, three, or four times IHH using a chamber flight. All exposed groups were treated hypobaric equivalent to: 35 000 ft altitude (one minutes), 25 000 ft (five minutes), and 18 000 ft (25 minutes). Protein MnSOD and Caspase-3 expression on mice heart cell were detected by Western Blot methods. In regard to protein MnSOD expressions, subjects with four time IHH exposures had likely similar level of oxidative stress (p=0.4057) compared with control groups. However, in term of protein Caspase-3 expressions, subjects with one, two times IHH exposures had increased apoptosis (p=0.0000; p=0.0001 respectively); three and four time exposures had decreased apoptosis (p=0.0187; p=0.0001 respectively). In conclusion, oxidative stress and apoptosis cell started to decrease after three-time IHH exposures in Sprague Dawley male mice. J Indon Med Assoc.2011;61:289-92.Keywords: intermittent hypobaric hypoxia, MnSOD, Caspase-3, Sprague Dawley Male Mice
Pajanan Hipoksia Hipobarik Intermiten Menurunkan Metabolisme Anaerobik pada Tikus Jantan Spraque Dawley Hidayat, Achmad; Wiradisastra, Kahdar; Hernowo, Bethy S.; Achmad, Tri Hanggono
Jurnal Kedokteran Maranatha Vol 10, No 1 (2010)
Publisher : Universitas Kristen Maranatha

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Hipoksia hipobarik intermiten (HHI) sering dialami oleh para penerbang maupun awak pesawat. Jika hipoksia berlanjut, maka terjadi metabolisme anaerobik yang berlebihan dan gangguan pada mitokondria yang menyebabkan apoptosis. Penelitian ini bertujuan menganalisis efek pajanan HHI terhadap metabolisme anaerobik dengan mengukur ekspresi LDH dan kadar asam laktat sebagai indikator glikolisis serta ekspresi caspase-3 untuk melihat apoptosis sel. Dilakukan penelitian eksperimental selama periode Januari-April 2010 pada tikus jantan Spraque Dawley yang dipajankan HHI satu sampai empat kali dengan interval satu minggu. Satu kelompok kontrol tidak dipajankan hipobarik hipoksia sedangkan empat kelompok perlakuan dipajankan pada hipobarik hipoksia menggunakan type I chamber flight profile (ruang udara bertekanan rendah – RUBR) dengan modifikasi. Tekanan RUBR disesuaikan setara ketinggian 35.000 kaki selama 1-2 menit, 25.000 kaki selama 5 menit, dan 18.000 kaki selama 25 menit. Hasil penelitian menunjukkan kadar asam laktat menurun dengan semakin seringnya tikus terpajan HHI. Ekspresi protein LDH dan Caspase-3 dengan imunohistokimia dan Western Blot juga menurun dengan semakin seringnya tikus terpajan hipoksia hipobarik. Terdapat korelasi antara penurunan ekspresi protein LDH dan Caspase-3 (r = 0,522; p=0,0031). Simpulannya adalah pajanan HHI menurunkan metabolisme anaerobik yang ditandai dengan penurunan glikolisis dan apoptosis pada tikus jantan jenis Spraque Dawley.Kata kunci: hipoksia hipobarik intermiten, metabolisme anaerobik, LDH, asam laktat, Caspase-3
Ekspresi Bcl-2 dan Caspase-3 Pascapaparan Hipoksia Hipobarik Intermiten Hidayat, Achmad; Wiradisastra, Kahdar; Hernowo, Bethy S.; Achmad, Tri Hanggono
Majalah Kedokteran Bandung Vol 43, No 4 (2011)
Publisher : Fakultas Kedokteran, Universitas Padjadjaran

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Abstract

Hipoksia hipobarik intermiten sering dialami oleh awak pesawat, karena selama di dalam kabin pesawat bernapas dengan tekanan udara yang lebih rendah. Tubuh akan beradaptasi dengan cara mengikat oksigen lebih banyak dan juga mengurangi dampak hipoksia. Fungsi mitokondria akan terganggu pada hipoksia, yaitu permiabilitas membran luar mitokondria karena protein Bcl-2 menurun. Jika hipoksia berlanjut akan terjadi kebocoran membran mitokondria, pelepasan sitokrom-c, dan proses apoptosis berlangsung. Penelitian ini bertujuan menganalisis protein Bcl-2 sebagai antiapoptosis dan caspase-3 sebagai indikator apoptosis akibat paparan hipoksia hipobarik intermiten. Dilakukan penelitian eksperimental pada tikus jantan Spraque Dawley periode Januari–April 2010 dengan melakukan paparan hipoksia hipobarik intermiten satu sampai empat kali dengan interval satu minggu. Jantung tikus dijadikan spesimen untuk dilakukan pemeriksaan ekspresi protein dengan pulasan imunohistokimia di Departemen Patologi Anatomi RS Dr. Hasan Sadikin Bandung dan western blot di Bagian Biomolekuler FK Universitas Indonesia Jakarta. Ekspresi protein Bcl-2 meningkat sesuai dengan frekuensi paparan hipoksia hipobarik intermiten, sebaliknya ekspresi protein caspase-3 menurun (rs=-0,448, p=0,013). Dari penelitian ini dapat disimpulkan bahwa terjadi penurunan tingkat apoptosis akibat paparan hipoksia hipobarik intermiten, hal ini disebabkan mekanisme adaptasi natural yang ditandai dengan menurunnya apoptosis sel dan secara tidak langsung akan memberi efek kardioprotektif. [MKB. 2011;43(4):166–70].Kata kunci: Apoptosis, Bcl-2, caspase-3, hipoksia hipobarik intermitenBcl-2 and Caspase-3 Expression Post Exposure of Intermittent Hypobaric HypoxiaIntermittent hypobaric hypoxia often suffered by cabin crew due to the fact that they are breathing lower pressured air inside the plane cabin. Human body will adapt by binding more oxygen and reducing hypoxia effect. Mitochondria function will be irritated by hypoxia which affect, outer mithochondrial membrane permeability due to decrease of Bcl-2 protein. Later on if hypoxia continues mitochondrial membrane will leaked cytocrome-c will released and apoptotic pathway will occur. The purpose of this study was to analyze Bcl-2 protein as antiapoptosis and caspase-3 as apoptosis indicator of intermittent hypobaric hypoxia exposure. Experimental study >was subjected to Spraque Dawley male mice during January–April 2010 by exposing them to several intermittent hypobaric hypoxias (one to four treatment) in an interval of one week. Protein expression on mice heart cell were detected by immunohistochemistry in the Department of Pathology Anatomy Padjadjaran University-RS Dr. Hasan Sadikin Bandung and western blot methods in Department Biomolecullar Indonesia University Jakarta. Bcl-2 protein expressions increased according with the frequency of intermittent hypobaric hypoxia exposures while a reverse trend was found for caspase-3 protein expressions (rs=-0.448, p=0.013). From the study it can be concluded that apoptosis will be decreased as a result of intermittent hypobaric hypoxia exposures, which occurred from natural adaptation mechanism indicated by decrease of cell apoptosis and cardio protective effect will be emerged. [MKB. 2011;43(4):166–70].Key words: Apoptosis, Bcl-2, caspase-3, intermittent hypobaric hypoxia