Proximal tubule cell response to radiographic contrast media

Renal dysfunction associated with contrast media (CM) administration is generally attributed to reduced renal blood flow. Studies, however, also suggest direct tubular effects of CM, whose mechanisms remain unclear. This study was conducted to assess the chemotoxic effects of iopamidol, a prototypic CM, on a porcine proximal tubule (PT) cell line, LLC-PK 1 cells. Results indicate that iopamidol did not affect cell viability (determined by trypan blue exclusion and fluorescein staining), but did reduce cell proliferation. Moreover, iopamidol altered mitochondrial function, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and mitochondrial membrane potential. Decreased MTT reduction was evident with all CM tested, and its rapid recovery after CM removal suggests that inhibition of mitochondrial function is reversible. Injury to PT cells by iopamidol is supported by the fact that CM increase extracellular adenosine, an indicator of cellular stress. This study provides greater insight into the mechanism underlying the nephrotoxicity induced by contrast in patients and explains the reversibility of this toxicity.