Lithium interferes with the urinary excretion of phenolsulfonphthalein in rats: involvement of a reduced content of α-ketoglutarate, the driving force for organic anion transporters OAT1 and OAT3, in the kidney cortex
Lithium interferes with the urinary excretion of phenolsulfonphthalein in rats: involvement of a reduced content of α-ketoglutarate, the driving force for organic anion transporters OAT1 and OAT3, in the kidney cortex
复制标题
锂干扰大鼠酚磺酞的尿排泄：涉及肾皮质中 α-酮戊二酸含量的减少，α-酮戊二酸是有机阴离子转运蛋白 OAT1 和 OAT3 的驱动力
作者：
Uwai;Y.;Tsuge;M.;Tokai;Y.;Kawasaki;T.;Nabekura;T.
AimsLithium对双相情感障碍的治疗有效，并且已知会影响肾功能。方法采用大鼠药代动力学实验和Western blotting方法，观察锂对大鼠肾脏有机阴离子转运系统的影响。结果静脉推注酚磺酞（一种肾脏有机阴离子转运蛋白的典型底物）后60 min，尿中回收的剂量为41.2%，并且氯化锂的输注剂量依赖性地干扰其肾排泄。大鼠有机阴离子转运体rOAT 1和rOAT 3的表达水平无明显变化，而这两种转运体的驱动力α-酮戊二酸的含量则明显降低。结论锂对大鼠肾脏有机阴离子转运系统有一定的损害作用。作为机制，认为至少部分涉及rOAT 1和rOAT 3的驱动力降低。
AimsLithium is effective in the treatment for bipolar disorder and is known to influence renal functions. The purpose of this study was to examine the effects of lithium on the renal organic anion transport system.MethodsPharmacokinetic experiments using rats and Western blotting were conducted.ResultsUntil 60 min after the intravenous injection of phenolsulfonphthalein, a typical substrate of the renal organic anion transporters, as a bolus, 41.2% of the dose was recovered in the urine, and the infusion of lithium chloride dose-dependently interfered with its renal excretion. No significant changes were observed in the expression levels of rat organic anion transporters rOAT1 and rOAT3, and the content of α-ketoglutarate, the driving force for both transporters, was significantly decreased in the kidney cortex of rats administered lithium.ConclusionThese findings represented the dysfunction of the renal organic anion transport system in rats by lithium. As the mechanism, the reduced driving force for rOAT1 and rOAT3 was suggested to be involved at least in part.