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논문분류	춘계학술대회 초록집
제목	In vitro Effect of Statins on Intracellular Cyclosporine A Concentration in Human Peripheral Blood Mononuclear Cells
저자	Seok Ju Park1, Sun Woo Kang1, Tae Hee Kim1, Mi Sun Kang2
출판정보	2013; 2013(1):
키워드	스타틴, 시클로스포린/Statin, Cyclosporine
초록	Background: It was known that declining intracellular T-lymphocyte concentration of cyclosporine A precedes acute rejection in kidney transplant recipients. The aim of this study was to elucidate the impact of various statins on intracellular cyclosporine A concentration in the PBMC (peripheral blood mononuclear cell). Method: PBMCs were isolated from 30 ml of freshly collected blood which were obtained from healthy 4 volunteers with informed consent. PBMC were incubated in the media with 0.1 ml of ND96 buffer containing 200 nm of cyclosporine A in the presence and absence of rosuvastatin (10 μm, 100 μm), simvastatin (10 μm, 100 μm), atorvastatin (10 μm, 100 μm), fluvastatin (10 μm, 100 μm), pitavastatin (10 μm, 100 μm) for 30 min at 37℃. The radioactivity was measured by a MicroBeta TriLux 96-well Scintillation/Luminescence detector (PerkinElmer). We also measured intracellular cyclosporine A concentration in the presence of the statins (100 μm) in the LLC-PK1 overexpressing P-glycoprotein cells. Result: The intracellular concentration of cyclosporine A in the control and in the presence of verapamil was 30.5±6.2 fmol/min/2×105 and 55.8±6.4 fmol/min/2×105 (p=0.008) respectively. The intracellular cyclosporine A concentration with simvastain (10μm, 100 μm) and with atorvastatin (10μm, 100 μm) showed significant higher value, 67.1±6.7 fmol/min/2×105 (p=0.002), 66.2±4.5 fmol/min/2×105 (p=0.001), 45±4.9 fmol/min/2×105 (p=0.03), 57.5±2 fmol/min/2×105 (p=0.002),respectively. But the others were not (p>0.05). It also revealed higher intracellular cyclosporine A concentrations in the presence of verapamil, atorvastatin and simvastatin, 398.7±1.1 fmol/min/1×104 (p= 0.0002), 108.3±0.6 fmol/min/1×104 (p=0.04), 222±0.8 fmol/min/1×104 (p=0.01), respectively, in the LLC-PK1 cells. Conclusion: The intracellular cyclosporine A concentration could be affected variously with statins by p-glycoprotein mediated inhibition.
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