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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Effects of serum lipoproteins on cyclosporine A cellular uptake and renal toxicity in vitro
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Effects of serum lipoproteins on cyclosporine A cellular uptake and renal toxicity in vitro

机译:血清脂蛋白对环孢素A细胞摄取和体外肾毒性的影响

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In-vitro studies were performed to shed light on previous findings that showed increased uptake of cyclosporine A in the kidneys and liver of hyperlipidemic rats, and increased signs of kidney toxicity. Hepatocytes were obtained from rats, cultured, and exposed to a diluted serum from hyperlipidemic rats. Some cells were also exposed to lipid-lowering drugs. After washing out the rat serum or lipid-lowering drugs, cells were exposed to cyclosporine A embedded in serum lipoproteins. Pretreatment with hyperlipidemic serum and lipid-lowering drugs was associated with an increased uptake of cyclosporine A. As expected, atorvastatin caused an increase in low density lipoprotein receptor and a decrease in MDR1A mRNA in the hepatocytes. A decrease in NRK-52E rat renal tubular cellular viability caused by cyclosporine A was noted when cells were preincubated with diluted hyperlipidemic serum. This was matched with evidence of hyperlipidemic-serum-associated increases in the NRK-52E cellular uptake of cyclosporine A and rhodamine-123. The findings of these experiments suggested that in hyperlipidemia the expression and (or) the functional activity of P-glycoprotein was diminished, leading to greater hepatic and renal uptake of cyclosporine A, and renal cellular toxicity.
机译:进行了体外研究以阐明先前的发现,这些发现表明高脂血症大鼠肾脏和肝脏中环孢菌素A的摄取增加,并且肾脏毒性的迹象增加。从大鼠获得肝细胞,进行培养,并暴露于高脂血症大鼠的稀释血清中。一些细胞还暴露于降脂药物。冲洗掉大鼠血清或降脂药物后,将细胞暴露于包埋在血清脂蛋白中的环孢素A。高脂血症血清和降脂药的预处理与环孢菌素A的摄取增加有关。正如预期的那样,阿托伐他汀引起肝细胞中低密度脂蛋白受体的增加和MDR1A mRNA的减少。当将细胞与稀释的高脂血症血清预孵育后,会注意到由环孢菌素A引起的NRK-52E大鼠肾小管细胞活力的降低。这与高脂血症血清相关的环孢素A和若丹明123的NRK-52E细胞摄取增加的证据相符。这些实验的发现表明,在高脂血症中,P-糖蛋白的表达和(或)功能活性降低,导致更大的肝和肾对环孢菌素A的摄取,以及肾细胞毒性。

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