Effects of radiologic contrast media on human endothelial and kidney cell lines: intracellular pH and cytotoxicity.
OBJECTIVE
Radiologic contrast media (CM) are hyperosmotic compounds injected undiluted into a patient's blood, in which they contact endothelial cells. For some types of cultured cells, the application of a hyperosmotic stimulus may cause intracellular pH (pHi) acidification that is related to the extent of hyperosmolality and that ultimately influences cellular function. Accordingly, endothelial and kidney cells, two types of cells known to be exposed to CM effects, were treated at relevant iodine concentrations with various CM (320-1500 mOsm) to determine whether cell exposure to CM can disturb the pH(i) and to examine the contribution of CM to cellular cytotoxicity.


METHODS
Ionic (n = 3) and nonionic (n = 3) CM were compared. Changes in the pH(i) of human vascular endothelial and kidney cell lines were monitored by use of a pH-sensitive fluorescent dye (2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester). The viability of cells treated with CM was determined by measuring the reduction of a tetrazolium salt (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenlytetrazolium bromide) to violet formazan, a reaction that requires the activity of mitochondrial dehydrogenase; this measurement was made with a microplate reader.


RESULTS
The pH(i) of endothelial and kidney cells exposed to 40-60 mg of iodine per milliliter of CM showed acidification (approximately 0.2 pH unit). Within minutes, gradual pH(i) alkalinization to baseline values occurred. The return to baseline values was slower with ionic compounds than with nonionic CM (P < 0.001). Nonionic agents caused less cellular damage than did ionic CM.


CONCLUSIONS
The pH(i) is involved in the immediate intracellular transduction of CM effects in vitro. The exposure of cells to ionic CM is more detrimental than is exposure to nonionic CM, as demonstrated by disturbances in the cytosolic pH and by long-term effects on cell viability.
Dascalu
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Department of Physiology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Peer
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D000230:Adenocarcinoma; D002460:Cell Line; D003287:Contrast Media / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007680:Kidney Neoplasms; D009994:Osmolar Concentration; D010084:Oxidation-Reduction / Q000187:drug effects; D013778:Tetrazolium Salts / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured; D014470:Umbilical Cord
D003287:Contrast Media; D013778:Tetrazolium Salts