Radiocontrast-induced renal tubular cell apoptosis: hypertonic versus oxidative stress.
OBJECTIVE
Radiocontrast-induced nephropathy (RCIN) is a major complication of intravascular radiocontrast administration. Renal tubular cell apoptosis is a feature of RCIN, which is related to hypertonicity of contrast agents. Because a hyperosmolal extracellular environment induces oxidative stress via reactive oxygen species, we tested the hypothesis that antioxidants decrease hypertonicity-induced apoptosis of renal epithelial cells. We analyzed the effects of the antioxidants N-acetylcysteine (NAC) and taurine on hypertonicity-induced apoptosis of renal epithelial cells in vitro.


METHODS
Madin Darby Canine Kidney (MDCK) cells were incubated with the highly hyperosmolal, ionic radiocontrast agent diatrizoate (20% vol/vol, 6 hours) or with equally hyperosmolal (640 mOsm/kg) NaCl solutions. DNA fragmentation, which is a hallmark feature of apoptosis, was assessed quantitatively using flow cytometry after propidium iodide staining and qualitatively using agarose gel electrophoresis.


RESULTS
Both diatrizoate and NaCl induced DNA fragmentation in MDCK cells. Taurine (10 mmol/L) reduced DNA degradation in both diatrizoate- [79.5 +/- 2.3% versus 72.2 +/- 3.0%; P = 0.0088] and NaCl- [49.5 +/- 4.0% versus 39.4 +/- 1.0%; P = 0.0271] treated cells. In contrast, NAC (10 mmol/L) failed to reduce the DNA breakdown in this model of hypertonicity-induced renal tubular cell apoptosis.


CONCLUSIONS
The radiocontrast/hypertonicity-induced DNA fragmentation of MDCK cells is attenuated by taurine but not by NAC. Because both agents are antioxidants, the antioxidant property is not sufficient for the observed cytoprotective effect. Hence, the antiapoptotic effect of taurine has to be attributed to other, yet to be defined mechanisms. Our results suggest that pharmacological doses of taurine may be particularly protective against RCIN.
Hizoh
Istvan
I
Department of Cardiology and Internal Medicine, Semmelweis University, Budapest, Hungary.
Haller
Christlieb
C
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003287:Contrast Media; D053938:DNA Fragmentation; D003973:Diatrizoate / Q000494:pharmacology; D004285:Dogs; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D009994:Osmolar Concentration; D018384:Oxidative Stress; D012965:Sodium Chloride / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology
D003287:Contrast Media; D003973:Diatrizoate; D013654:Taurine; D012965:Sodium Chloride; D000111:Acetylcysteine