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Am J Physiol Renal Physiol 252: F246-F255, 1987;
0363-6127/87 $5.00
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AJP - Renal Physiology, Vol 252, Issue 2 246-F255, Copyright © 1987 by American Physiological Society

ARTICLES

Direct toxic effect of the radiocontrast agent diatrizoate on renal proximal tubule cells

H. D. Humes, D. A. Hunt and M. D. White

The pathophysiology of radiocontrast agent-induced acute renal failure is presently unclear. To test for a possible direct deleterious effect of diatrizoate, a commonly used radiocontrast agent, on renal tubule cells, suspensions enriched in rabbit proximal tubule segments were incubated with sodium diatrizoate. After these manipulations, a variety of well-established metabolic parameters to quantitate the extent of cell injury were measured. Diatrizoate sodium (25 mM) produced significant declines in tubule K+, ATP, and total adenine nucleotide (TAN) contents, significant decreases in tubule basal and uncoupled respiratory rates, and a significant increase in tubule Ca2+ content, demonstrating the development of cell injury induced by diatrizoate. These effects were dose related and were progressive with increasing incubation time from 97.5 to 157.5 min. The effects of N-methylglucosamine (meglumine) on renal tubule cell viability was also evaluated. Meglumine is a low molecular weight amino-substituted cationic compound and is commonly added to radiocontrast dye solutions. Meglumine (25 mM) had significant effects to lower tubule K+ content and to decrease both tubule basal and uncoupled respiratory rates. These alterations were slightly additive to diatrizoate in that meglumine diatrizoate produced greater alterations in tubule-metabolic parameters compared to diatrizoate sodium. A period of 22.5 min of hypoxia also caused deleterious changes in each of these quantitative indices of cell viability, and diatrizoate potentiated the degree of hypoxia-induced cell injury. These results demonstrate that the radiocontrast agent, diatrizoate, is directly toxic to renal proximal tubule cells. Meglumine, a cation added to diatrizoate containing radiocontrast solutions, also had a moderate toxic effect on renal epithelial cells and added to the toxicity of diatrizoate. Diatrizoate also aggravated the degree of cell injury induced by a 22.5-min period of hypoxia. These experiments thus provide evidence for a direct toxic effect of diatrizoate on proximal renal tubule cells which was additive to hypoxic cell injury.


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