Comparison of the toxicity of the radiocontrast agents, iopamidol and diatrizoate, to rabbit renal proximal tubule cells in vitro

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 244; no. 3; pp. 1139 - 1144
• Main Authors: MESSANA, J. M, CIESLINSKI, D. A, NGUYEN, V. D, HUMES, H. D
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.03.1988
• Subjects: Adenosine Triphosphate - analysis; Analysis of Variance; Animals; Biological and medical sciences; Calcium - analysis; Diatrizoate - toxicity; Drug toxicity and drugs side effects treatment; Hypoxia - metabolism; In Vitro Techniques; Iopamidol - toxicity; Kidney Tubules, Proximal - analysis; Kidney Tubules, Proximal - drug effects; Medical sciences; Oxygen Consumption; Pharmacology. Drug treatments; Potassium - analysis; Rabbits; Toxicity: urogenital system; Vertebrata; Mammalia; Urinary system disease; Toxicity; Animal; Rabbit; Lagomorpha; Mechanism of action; In vitro; Proximal tube; Contrast media; Kidney
• ISSN: 0022-3565; 1521-0103

Radiographic contrast agent-induced acute renal failure is an increasingly recognized clinical event. Multiple factors have been implicated in its development. Recent experiments have demonstrated that sodium diatrizoate, a common ionic radiocontrast agent, is moderately toxic to proximal tubule cells in vitro, and that this toxicity is enhanced by hypoxia. In this study, we compare toxicities of the nonionic radiocontrast agent, iopamidol, and the commonly used ionic contrast agent, diatrizoate. Suspensions enriched in proximal tubule segments were exposed for 82.5 min to 10 or 25 mM diatrizoate or 10 or 25 mM iopamidol with or without 22.5 min or 30 min of hypoxia. Cell viability parameters, including basal and uncoupled respiratory rates, tubule cell potassium and calcium levels and cell ATP content were measured. No consistent differences in tubule viability parameters were observed between tubule suspensions exposed to 10 mM concentrations of the radiocontrast agents during either oxygenated or hypoxic conditions. Under oxygenated conditions, both 25 mM iopamidol and diatrizoate exposure produced greater metabolic alterations in renal tubules than control conditions, but the effects were not statistically significant. With concomitant hypoxia, the alterations after 25 mM diatrizoate exposure were significantly greater than those seen after exposure to 25 mM iopamidol. Iopamidol had less of a detrimental effect on renal tubule potassium content and both basal and uncoupled respiratory rates than that of diatrizoate under these conditions. Thus, diatrizoate is more toxic to rabbit renal proximal tubule cells than iopamidol in vitro, and this difference in toxicity is enhanced by hypoxia.