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

Figures & data

Table 1.  Physicochemical properties for iodixanol, iohexol, iopromide, and ioversol

X-ray contrast agent	mOsm/kg undiluted	mOsm/kg (150 mg I/ml)	Molecular weight
Iodixanol	290 (320 mg I/mL)	350	1550
Iohexol	780 (350 mg I/mL)	559	821
Iopromide	610–620 (300 mg I/mL)	530	791
Ioversol	630 (300 mg I/mL)	531	807

Sources: osmolality undiluted was adapted from Davidson et al.,¹² whereas osmolality at 150 mg I/mL (diluted in incubation medium) was measured on a Wescor 5520 XR Vapor Pressure Osmometer ( ELITech Biomedical Systems, Puteaux, France), the solutions were measured in four replicates and the mean is reported. Molecular weights are adapted from Morcos.¹³

Table 2.  Cell death (%, mean ± SEM), measured by the trypan blue exclusion assay, in NRK 52-E cells after exposure to incubation medium (control), iodixanol, iohexol, iopromide, and ioversol (150 mg I/mL)

	1 h	3 h	6 h	12 h	24 h
Control (I)	7.20 ± 0.51	7.15 ± 0.65	7.20 ± 0.63	6.10 ± 0.26	7.72 ± 0.56
Iodixanol (II)	4.00 ± 0.32*	4.00 ± 0.32	6.00 ± 1.00	11.40 ± 1.29	33.60 ± 2.58*
Iohexol (III)	5.00 ± 0.89	4.60 ± 0.68	2.75 ± 0.25*	48.60 ± 5.38*	81.40 ± 1.57*
Iopromide (IV)	6.00 ± 0.55	6.20 ± 0.74	7.20 ± 0.37	37.20 ± 0.86*	55.00 ± 5.40*
Ioversol (V)	9.80 ± 1.53	12.40 ± 2.11*	12.40 ± 1.25*	42.40 ± 1.47*	57.70 ± 2.62*
Significance**	II vs. V	II vs. V	II vs. V	II vs. III	II vs. III
	III vs. V	III vs. V	III vs. IV	II vs. IV	II vs. IV
	IV vs. V	IV vs. V	III vs. V	II vs. V	II vs. V
			IV vs. V	III vs. IV	III vs. IV
				III vs. V	III vs. V

Note: *Statistically significant difference relative to control (one-way ANOVA with Dunnet's post hoc test, 4 ≤ n ≤ 5 for the ICM groups and 20 for the control group, p < 0.05); **statistically significant difference in pairwise comparison (Duncan's method, p < 0.05).

Table 3.  Cell viability (percent of control, mean ± SEM), as determined by mitochondrial dehydrogenase activity, in NRK 52-E cells after exposure to incubation medium (control), iodixanol, iohexol, iopromide, and ioversol (150 mg I/mL)

	0.5 h	1 h	2 h	3 h	6 h	12 h	24 h
Control (I)	100.00 ± 0	100.00 ± 0	100.00 ± 0	100.00 ± 0	100.00 ± 0	100.00 ± 0	100.00 ± 0
Iodixanol (II)	34.91 ± 1.94	29.22 ± 1.01	30.50 ± 0.87	28.54 ± 0.74	31.76 ± 2.26	23.87 ± 0.56	21.71 ± 0.76
Iohexol (III)	44.69 ± 4.73	37.92 ± 2.35	39.77 ± 2.37	34.21 ± 1.87	35.36 ± 3.22	16.42 ± 0.57	5.59 ± 0.37
Iopromide (IV)	43.14 ± 3.23	35.18 ± 2.28	35.82 ± 2.24	31.64 ± 1.60	31.52 ± 2.12	21.02 ± 0.85	10.73 ± 0.94
Ioversol (V)	45.75 ± 2.15	41.67 ± 1.87	42.22 ± 1.10	36.15 ± 1.68	37.58 ± 2.43	26.21 ± 1.08	8.32 ± 0.33
Significance*		II vs. III	II vs. III	II vs. III		II vs. III	II vs. III
		II vs. IV	II vs. IV	II vs. V		II vs. IV	II vs. IV
		II vs. V	II vs. V			II vs. V	II vs. V
		IV vs. V	IV vs. V			III vs. IV	III vs. IV
						III vs. V	III vs. V
						IV vs. V	IV vs. V

Note: *Statistically significant difference, one-way ANOVA with Duncan's post hoc test, 5 ≤ n ≤ 8, p < 0.05.

Table 4.  Cell death (%, mean ± SEM) assessed on formalin-fixed NRK 52-E cells after exposure to incubation medium (control), iodixanol, iohexol, iopromide, and ioversol (150 mg I/mL) (n = 5: two counts from the first specimen and three from the last)

	Control	0.5 h	1 h	2 h	3 h	6 h	12 h	24 h
Iodixanol	5.76 ± 0.55	5.83 ± 0.39	4.94 ± 0.28	6.26 ± 0.16	9.00 ± 0.37	9.40 ± 0.65	16.16 ± 0.71	70.05 ± 0.70
Iohexol	5.70 ± 0.42	5.33 ± 0.54	7.44 ± 0.33	8.32 ± 0.44	14.60 ± 0.38	17.64 ± 1.34	29.41 ± 0.25	95.59 ± 0.70
Iopromide	5.97 ± 0.42	6.11 ± 0.38	7.75 ± 0.39	8.52 ± 0.46	13.20 ± 0.24	15.52 ± 0.50	27.32 ± 1.15	92.99 ± 0.85
Ioversol	5.43 ± 0.73	5.34 ± 0.30	7.02 ± 0.41	9.09 ± 0.54	14.13 ± 1.00	18.09 ± 0.83	32.83 ± 1.07	93.51 ± 0.67

Figure 1. (A) Hematoxylin-stained NRK 52-E cells (control – incubation media treated) (×200). Note the confluence of the cell layer. Randomly scattered throughout the culture are cells that have separated from the surrounding cells and contain condense dark nuclei (arrows). These are degenerating/dying cells. (B) Hematoxylin-stained NRK 52-E cells after 1 h exposure to 150 mg I/mL ioversol (×400). Note the increased number of dead cells scattered throughout the cell culture layer. (C) Hematoxylin-stained NRK 52-E cells after 3 h exposure to 150 mg I/mL ioversol (×400). There are more necrotic cells and the confluence of the cell culture layer is lost. (D) Hematoxylin-stained NRK 52-E cells after 12 h exposure to 150 mg I/mL ioversol (×400). Note that almost all the cells are either necrotic or dying. Also cell-to-cell contact is minimal.

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