The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

Abstract

Nephrotoxicity, associated with the administration of iodinated X-ray contrast media (ICM), continues to be a major side effect in a significant number of vulnerable patients undergoing diagnostic X-ray imaging procedures. The molecular mechanisms underlying these adverse effects on the kidneys are unclear despite several decades of investigation. Side effects are more common after exposure to high-osmolar compared with low-osmolar ICM, suggesting that osmolality may be an important physical-chemical property related to nephrotoxicity. This investigation in cultured NRK 52-E cells, a cell line of renal origin, compares the in vitro toxicity of the iso-osmolal ICM iodixanol with the lowosmolal ICM iohexol, iopromide, and ioversol. The cellular toxicity was evaluated with the trypan blue exclusion assay, the MTT assay, and incidences of cell death. A qualitative assessment of vacuolation of the cultured NRK 52-E cells was taken as a measure of intracellular uptake of ICM. A difference in cell death incidence was observed between the iso-osmolal iodixanol and the low-osmolal iohexol, iopromide, and ioversol contrast media, with the isoosmolal iodixanol having the least effect in each of the in vitro systems tested. The osmolality of the contrast media appeared to be the major cause for the observed in vitro toxicity.

The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM)

“…Increasing apoptosis by hematoxylin-stained. [ 60 ] NRK52-E (Rat tubular cells) Iohexol (Omnipaque) 100 mgI/ ml 24 h 1. Decreasing cell proliferation by MTT assay.…”

Potential and Limits of Kidney Cells for Evaluation of Renal Excretion

“…However, our own previous studies and those of others [ 14 , 15 , 16 , 17 ] demonstrated the rather diverse expression of transport proteins dependent on the subtype of MDCK cells. NRK-52 cells have also widely been used mainly for toxicological studies [ 18 , 19 , 20 ]; however, to date, detailed cell characteristics have not been published. The same is the case for IHKE-1 cells.…”

A Novel Contrast-Induced Acute Kidney Injury Model Based on the 5/6-Nephrectomy Rat and Nephrotoxicological Evaluation of Iohexol and IodixanolIn Vivo

“…Jensen et al [29] reported that LOCM induced more markedly direct toxic effect on tubular epithelial cells than IOCM. This is consistent with our result.…”