The effects of the iodinated X-ray contrast media iodixanol, iohexol, iopromide, and ioversol on the rat kidney epithelial cell line NRK 52-E.

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 low-osmolal 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 iso-osmolal 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.

A modified model of gentamicin induced renal failure in rats: toxicological effects of the iodinated X-ray contrast media ioversol and potential usefulness for toxicological evaluation of iodinated X-ray contrast media.

Contrast-induced nephropathy (CIN) remains a serious complication in patients exposed to iodinated X-ray contrast media (ICM). Animal models of CIN are useful to further understand the mechanisms involved, identify novel biomarkers and evaluate potential differences between ICM. The current investigation was undertaken to modify the rat-gentamicin model for potential usefulness for toxicological evaluation of ICM. A dose-range finding study (50, 60 and 70 mg/kg body weight (bw)) of gentamicin was conducted over 4 consecutive days. Based on the kidney histopathology findings, a gentamicin dose of 70 mg/kg bw was chosen to investigate whether ICM would cause further renal damage. Following gentamicin treatment, this group was given a single administration of ioversol (6 gI/kg bw). Blood and urine samples were taken from all animals 3 days before the start of the study and at the end of treatment. Serum and urinary creatinine, urinary N-acetyl-ß-D-glucosaminidase (NAG), γ-glutamyl transferase (GGT), total protein, and urine cytology were evaluated as biomarkers of renal damage. Histopathological examination of kidneys was performed. Histopathological examination of the kidneys revealed vacuolation, dilatation, and necrosis of the proximal tubules in the gentamicin-ioversol treatment group. These changes were not seen in the gentamicin-only treatment groups. Data on GGT and urinary epithelial cells show clear differences between rats treated with gentamicin alone versus gentamicin plus ioversol. These findings show that the modified rat-gentamicin model was able to demonstrate the nephrotoxic effect of ioversol.