KB-R7943 decreased renal tubular call apoptosis and p38 expression Induced by contrast media

Objective To investigate whether intraeellular Ca2+ overload via NCX system and p38MAPK contributes to the contrast media nepbrotoxicity and whether KB-R7943,an inhibitor of reverse mode of Na+/Ca2+ exchanger,attenuates contrast media-inducod tubular cell injury and inhibits the expression of p-p38.Methods The tubular cells were treated with KB-R7943 at various concentrations 1 h before contrast media administration.Lactic dehydrogenase (LDH) was determined to evaluate the cell damage severity.Flow cytometry was used to quantify the apoptotic cells.Morphologic change of tubular cell was observed by inverted microscope and intracellular Ca2+ concentration was detected by fluorescence probe using confocal microscope.The expression of p-p38 protein was examined by Western blot.The expression of Na+/Ca2 + exchanger mRNA was evaluated by reverse transcription-polymerase chain reaction.Results Contrast media induced significantly increased LDH level in the culture media and apoptotic tubular cells.Intraeellular Ca2 + concentration was also increased progressively following contrast media administration.The expression of p-p38 protein was increased significantly at 30 min and decreased at 60 min in contrast media group.The expression of Na+/Ca2+ exchanger mRNA had no change at 30 min and 60 min.KB-R7943 attenuated the cell injury,decreased the tubular cell apoptosis and inhibited the increased expression of p-p38 protein induced by contrast media through decreasing intracellular Ca2+ overload.Conclusion Intracellular Ca2+ overload via the NCX system contributed to the contrast media-induced nephrotoxicity;KB-R7943 exerted renoprotective effects through decreasing intracellular Ca2+ overload and inhibiting the expression of p-p38 protein. Key words: Contrast media; Tubular epithelial cells; KB-R7943; p38 mitogen-activated protein kinase