Characterization of a novel model for investigation of radiocontrast nephrotoxicity.
OBJECTIVE
Radiocontrast agents are one of the most common causes of acute renal failure in the world. These agents are required for both diagnostic and therapeutic modalities of medical intervention, including computed tomography (CT), angiography and cardiac catheterization. Publications over the past 40 years support three potential mechanisms of toxicity: oxidative stress, haemodynamics and hyperosmolar effects. An in vitro model provides a rapid evaluation of cellular toxicity without the complications of haemodynamics. This study evaluated the renal toxicity of radiocontrast agents at clinically relevant concentrations.


METHODS
This study investigated the toxicity of two radiocontrast agents, diatrizoic acid (DA) and iothalamic acid (IA), using an in vitro model. Renal cortical slices isolated from F344 rats were incubated with 0-111 mg I/ml DA or IA.


RESULTS
Renal slices exposed to DA and IA showed toxicity as measured by increased lactate dehydrogenase (LDH) leakage at concentrations lower than previously published using isolated cell models. These data indicate that DA and IA are toxic to renal cortical slices, and this is a more sensitive model than previously used cell culture systems. DA and IA treatment failed to cause a significant decrease in total cellular glutathione or increase in percent glutathione disulphide (GSSG), implying that oxidative stress may not be an initial mechanism of toxicity. Finally, the addition of exogenous glutathione did provide complete protection from DA- and IA-induced LDH leakage.


CONCLUSIONS
These data validate the renal cortical slice in vitro model for investigation of radiocontrast nephrotoxicity. These studies further showed that glutathione was cytoprotective. Future research using this model is aimed at further characterization of radiocontrast nephrotoxicity, which may allow for improved prevention and treatment of radiocontrast-induced acute renal failure.
Department of Pharmacology, Marshall University School of Medicine, WV 25755-9388, USA.
Robert C
RC
Harmon
Scott P
SP
Duffy
Marcus V
MV
Terneus
John G
JG
Ball
Monica A
MA
Valentovic
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects* / Q000494:pharmacology; D003973:Diatrizoate / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007483:Iothalamic Acid / Q000009:adverse effects* / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D046509:Tissue Culture Techniques
D003287:Contrast Media; D003973:Diatrizoate; D007483:Iothalamic Acid