Hasil Pencarian  ::  Simpan CSV :: Kembali

Abstrak :
Latar Belakang: Penelitian yang dilakukan bertujuan untuk mengetahui secara lebih mendalam mekanisme molekuler fenomena respons adaptasi pada penduduk Mamuju, Sulawesi Barat sebagai area radiasi latar tinggi (high background radiation area/HBRA) di Indonesia khususnya ditinjau dari jalur inflamasi dan stress oksidatif. Metode: Penduduk Dusun Tande-Tande, Mamuju sebagai area radiasi latar tinggi dan penduduk Desa Topoyo, Mamuju Tengah sebagai kelompok kontrol direkrut dalam penelitian. Pemeriksaan kerusakan DNA, aberasi kromosom tidak stabil, stabil, mikronukleus, indeks mitosis, nuclear division index, aktivitas enzim SOD, GPx konsentrasi CAT serum dan darah lengkap dilakukan pada penelitian. Analisis G2 MN dilakukan untuk memvalidasi respons adaptasi pada penduduk Dusun Tande-Tande. Pengukuran konsentrasi sitokin dan protein pro-inflamasi, anti-inflamasi, p-Akt, Akt, dan NFkB dilakukan untuk mengetahui keterlibatan jalur inflamasi dan stress oksidatif pada fenomena respons adaptasi. Hasil: Analisis kerusakan DNA, aberasi kromosom tidak stabil, stabil, aktivitas SOD, aktivitas GPx menunjukkan tidak terdapat perbedaan yang bermakna antara kedua kelompok penelitian. Rerata konsentrasi CAT kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Nilai indeks mitosis dan nuclear division index (NDI) pada kelompok kasus lebih tinggi secara bermakna dibandingkan kelompok kontrol. Rerata konsentrasi sitokin proinflamasi dan anti-inflamasi pada serum kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Rerata konsentrasi protein marker inflamasi CRP pada serum kelompok kasus lebih rendah tetapi tidak bermakna secara statistik dibandingkan kelompok kontrol. Hasil pemeriksaan darah lengkap memperlihatkan bahwa jumlah sel darah merah kelompok kasus lebih tinggi secara bermakna sedangkan jumlah limfosit, nilai MCV, MCH, MCHC, dan RDW kelompok kasus lebih rendah secara bermakna dibandingkan kelompok kontrol. Rerata nilai rasio p-Akt/Akt dan konsentrasi NFkB kelompok kasus lebih rendah secara bermakna dibandingkan dengan kelompok kontrol. Kesimpulan: Fenomena respons adaptasi terhadap radiasi terjadi pada penduduk Dusun Tande-Tande, Mamuju. Hasil penelitian belum dapat membuktikan peningkatan antioksidan serta sitokin tertentu baik sitokin pro maupun anti-inflamasi pada kelompok kasus. Aktivasi jalur Akt dan NFkB pada kelompok kasus belum dapat dibuktikan mengingat nilai rasio p-Akt/Akt serta konsentrasi NFkB lebih rendah secara bermakna dibandingkan dengan kelompok kontrol. ......Background: This study aim is to investigate the molecular mechanism of radioadaptive response in inhabitants of Mamuju, West Sulawesi as one of the high background radiation areas of Indonesia, particularly from inflammatory and oxidative stress perspectives. Methods: Tande-Tande sub-village, Mamuju district inhabitants as high background radiation areas, and Topoyo Village inhabitants in Middle Mamuju district were recruited in this study. Evaluation of DNA damage, unstable and stable chromosomal aberrations, micronucleus, mitotic index, nuclear dividon index, SOD and GPx activities, serum catalase concentration and complete blood count were performed in this study. The G2 MN assay for validating the radioadaptive response phenomenon was performed in this study. Measurement of pro and anti-inflamamatory cytokines, p-Akt, AKt and NFkB were performed to find out the involvement of infllmation and stress oxidative on radioadaptive response phenomenon. Results: The levels of DNA damage and stable and unstable chromosomal aberrations were not significantly different between the two groups. The rate of cell proliferation represented by the mitotic and nuclear dividion indexes showed a significantly higher rate in the case group. The SOD and GPx activities were not significantly different between the two groups. Interestingly, the CAT concentration was significantly lower in the case group. A significant lower level of both pro- and anti-inflammatory cytokines was also found in the case group. A lower level of CRP concentration as an inflammatory marker protein also showed in the present study, although it was not statistically significant. The complete blood counts analysis revealed a significant increase in RBC numbers and a significant decrease in lymphocyte numbers (MCV, MCH, MCHC, and RDW values) in the case group. The p-Akt/Akt ratio and NFkB concentration were also found to be statistically lower in the case group. Conclusion: It can be concluded that the radioadaptive response phenomena induced by chronic low radiation dose exposure existed in Tande-Tande sub-village inhabitants. However, this present study failed to find a significant increase of antioxidant enzymes and inflammatory cytokines in Tande-Tande sub-village inhabitants. The activation of Akt and NFkB pathways in Tande-Tande sub-village inhabitants was also not found in this present study.

Abstrak :
Latar belakang: Nanopartikel perak (AgNPs) telah banyak diteliti karena aktivitas anti-inflamasinya yang berpotensi digunakan sebagai obat yang bekerja secara lokal di saluran gastrointestinal (GI) untuk pengobatan kolitis ulseratif. Namun, disolusi AgNPs secara masif dalam kondisi asam di lambung berpotensi menyebabkan serapan sistemik dan toksisitas. Pendekatan rasional harus dirancang untuk penargetan kolon secara selektif. Metode: Biomolekul alginat dipilih sebagai agen penstabil untuk radiosintesis dan penghantaran AgNPs karena bersifat biokompatibel, sensitif pH, dan polianionik. Radiosintesis dioptimalkan menggunakan Central Composite Design – Response Surface Methodology (CCD-RSM) yang melibatkan 20 percobaan tanpa penambahan isopropanol sebagai scavenger radikal hidroksil. Stabilitas nanosuspensi dievaluasi selama penyimpanan pada suhu 4°C kondisi gelap selama 40 hari. Disolusi AgNPs secara in vitro ditentukan dalam simulasi cairan lambung pH 1,2 selama 120 menit. Kemudian, serapan sistemik dan toksisitas AgNPs terstabilisasi alginat ditentukan setelah pemberian oral dosis berulang 14 hari pada mencit sehat dengan dosis bervariasi (2,5, 5,0, dan 10,0 mg/kg BB). Hasil: Radiosintesis berhasil mensintesis AgNPs terstabilisasi alginat tanpa penambahan isopropanol. Kondisi optimal diperoleh pada dosis iradiasi 20 kGy, konsentrasi precursor ion perak 7,78 mM, dan konsentrasi alginat 1,2 % (b/v) yang menghasilkan nilai konversi 65,43 % dengan konsentrasi AgNPs 480,9 ppm. Morfologi AgNPs berbentuk bulat dengan ukuran 10,25 ± 5,03 nm. Menariknya, alginat berperan ganda sebagai agen penstabil sekaligus agen pereduksi selama radiosintesis. Alginat juga berperan menstabilkan nanosuspensi hingga 67 ± 5 hari, dan meminimalkan disolusi pada kondisi asam pH 1.2 hingga kurang dari 1,5 % dalam periode disolusi 120 menit. Setelah administrasi oral dosis berulang 14 hari dosis 2,5 mg/kg BB, mencit sehat tidak menunjukkan tanda toksisitas. Perak tidak terdeteksi pada organ dalam, sedangkan penilaian hstopatologis untuk hepar dan kolon tidak berbeda bermakna dengan kelompok kontrol. Kesimpulan: Alginat berperan penting dalam radiosintesis AgNPs tanpa penambahan isopropanol. Alginat juga berperan sebagai agen penstabil yang baik untuk menjaga stabilitas selama penyimpanan dan mencegah disolusi dalam kondisi asam. Dosis 2,5 mg/kg BB dapat digunakan sebagai dosis referensi untuk penelitian lebih lanjut mengenai toksisitas/bioaktivitas AgNPs sebagai obat yang bekerja secara lokal di saluran gastrointestinal (GI) untuk pengobatan kolitis ulseratif. ......Background: Silver nanoparticles (AgNPs) have been extensively investigated due to their anti-inflammatory activity which potentially used as locally-acting drug in the gastrointestinal (GI) tract for treatment of ulcerative colitis. However, massive dissolution of AgNPs in acidic stomach potentially lead to systemic uptake and toxicity. Rational approaches must be designed for selectively targeting the colon. Methods: Biomolecule alginate was chosen as stabilizing agent for radiosynthesis and delivery of AgNPs due to its biocompatibility, pH sensitiveness, and polyanionic nature. Radiosynthesis was optimized using central composite design – response surface methodology (CCD-RSM) which involved 20 run experiments without addition of isopropanol as a hydroxyl radical scavenger. The stability of nanosuspension was evaluated during storage at 4°C under dark for 40 days. The in vitro dissolution of AgNPs was determined in simulated gastric fluid pH 1.2 for 120 min. Then, systemic uptake and toxicity of alginate-stabilized AgNPs were determined upon 14 days repeated dose oral administration in healthy mice at varied dose (2.5, 5.0, and 10.0 mg/kg BW). Results: Radiosynthesis had successfully synthesized alginate AgNPs without addition of isopropanol. The optimal condition was found at dose of 20 kGy, precursor silver ion of 7.78 mM, and alginate concentration of 1.2 % (w/v) which resulted the conversion yield of 65.43 % with concentration of AgNPs at 480.9 ppm. The AgNPs was spherical in shape at size of 10.25 ± 5.03 nm. Interestingly, alginate played dual role as stabilizing and reducing agent during radiosynthesis. The alginate allowed stabilization of nanosuspension for 67 ± 5 days, and also minimized the acid dissolution down to 1.5 % during 120 min dissolution time. Upon 14 days repeated dose oral administration of AgNPs at dose 2.5 mg/kg BW, the healthy mice did not showed toxicity sign. Silver was not detected in internal organ, while hstopathological scoring for liver and colon is not significantly different with control group. Conclusion: Alginate plays important role in radiosynthesis of AgNPs without addition of isopropanol. It also acts as good stabilizing agent for maintaining stability during storage and preventing dissolution in acidic condition. Dose of 2.5 mg/kg BW can be used as a reference dose for further research on toxicity/bioactivity of AgNPs as locally-acting drug in the gastrointestinal (GI) tract for treatment of ulcerative colitis.