Introduction:

Contrast induced acute kidney injury (CI-AKI) is a common clinical event. One key feature of CI-AKI is a toxic effect of contrast media on the tubular cells. We investigate the hypothesis that contrast media induce tubular cell death by generating oxidative stress and reducing nitric oxide.

Methods:

Isolated thick ascending limbs (TALs) from rats were perfused with either vehicle solution or iodixanol. Nitric oxide bioavailability and superoxide concentration were quantificated by the fluorescent dyes DAF-FM and dihydroethidium (DHE), respectively. Propidium iodide was used to estimate the cell death rate. The expression of oxidative stress related genes and the activity of superoxide dismutase (SOD) in tubuli were investigated using a microarry and the OxiSelect kit in an ex vivo setup.

Results:

Compared to the control group, iodixanol increased DHE fluorescence ratio in 4min, whereas tempol inhibited the increase by iodixanol. DAF-FM fluorescence intensity decreased by iodixanol and by L-NAME similarly within 12min. Propidium iodide intensity was significantly enhanced by iodixanol within 20min. Moreover, during total 4-hour perfusion, iodixanol increased propidium iodide intensity to 17.7±3.1%, while in control group was 7.0±1.0%. Only two of 84 investigated genes were differentially expressed in the tubuli. The SOD activity did not differ between iodixanol perfused rats and control animals.

Conclusion:

The study shows that contrast media decrease nitric oxide bioavailability and increase superoxide concentration, implying oxidative stress in TALs. TAL cells are damaged by contrast media. This damage is not because of changes in the expression of oxidative stress related genes or SOD activity.