|
KMID : 0811719980020010069
|
|
Korean Journal of Physiology & Pharmacology
1998 Volume.2 No. 1 p.69 ~ p.76
|
|
|
Effect of Cisplatin on Na＋/H＋ Antiport in the OK Renal Epithelial Cell Line
|
|
Jee Yeun Kim
Yang Saeng Park
|
|
|
Abstract
|
|
|
|
Cis-diamminedichloroplatinum II (cisplatin), an effective antitumor agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin in the renal proximal tubular transport system, OK cell line was selected as a cell model and Na+/H+ antiport activity was evaluated during a course of cisplatin treatment. The cells grown to confluence were treated with cisplatin for 1 hour, washed, and incubated for up to 48 hours. At appropriate intervals, cells were examined for Na+/H+ antiport activity by measuring the recovery of intracellular pH (pHi) after acid loading. Cisplatin of less than 50 μM induced no significant changes in cell viability in 24 hours, but it decreased the viability markedly after 48 hours. In cells exposed to 50 μM cisplatin for 24 hours, the Na+?dependent pHi recovery (i.e., Na+/H+ antiport) was drastically inhibited with no changes in the Na+?independent recovery. Kinetic analysis of the Na+?dependent pHi recovery indicated that the Vmax was reduced, but the apparent Km was not altered. The cellular Na+ and K+ contents determined immediately before the transport measurement appeared to be similar in the control and cisplatin group, thus, the driving force for Na+?coupled transport was not different. These results indicate that cisplatin exposure impairs the Na+/H+ antiport capacity in OK cells. It is, therefore, possible that in patients treated with a high dose of cisplatin, proximal tubular mechanism for proton secretion (hence HCO?3 reabsorption) could be attenuated, leading to a metabolic acidosis (proximal renal tubular acidosis).
|
|
|
KEYWORD
|
|
|
Na＋/H＋ antiport, Cisplatin, OK cell,
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|
|