Triggering of suicidal erythrocyte death by radiocontrast agents.
BACKGROUND
According to in vitro observations, gadolinium-containing magnetic resonance (MRT) contrast agents stimulate suicidal cell death or apoptosis. Similar to nucleated cells, erythrocytes may undergo suicidal death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the erythrocyte surface. Eryptosis is triggered by increased cytosolic Ca2+-activity. This study explored whether gadolinium-containing MRT contrast agents stimulate eryptosis.


METHODS
Annexin V-binding reflecting PS exposure and forward scatter reflecting cell volume were determined in erythrocytes within freshly drawn blood from patients (8female symbol, 3male symbol, 29-72 years) prior to and 10 min after administration of gadoterate meglumine (0.1 mmol kg(-1) b.w. Dotarem; six patients) or gadobenate dimeglumine (0.05 mmol kg(-1) bw Multi Hance; five patients). In a separate series, eryptosis was determined prior to and following in vitro incubation of erythrocytes from 16 blood donors for 4 h with gadoterate meglumine (5 mM Dotarem) or gadobenate dimeglumine (5 mM Multi Hance). Finally, eryptosis and Fluo3 fluorescence reflecting cytosolic Ca2+ were determined in vitro following exposure to Gd3+. Data were analysed using paired t-test or anova with Tukey's test as post-test.


RESULTS
The MRT contrast agents such as gadoterate meglumine (Dotarem) and gadobenate dimeglumine (Multi Hance) significantly increased the percentage of eryptotic cells. Moreover, in vitro exposure to gadoterate meglumine (5 mM), gadobenate dimeglumine (5 mM) or Gd3+ (1.9 microM) stimulated eryptosis in vitro. The effect of Gd3+ was paralleled by increase in cytosolic Ca2+-activity.


CONCLUSIONS
MRT contrast agents may stimulate suicidal erythrocyte death or eryptosis in vitro and in vivo.
Föller
M
M
Department of Physiology, University of Tübingen, Tübingen, Germany.
Sopjani
M
M
Schlemmer
H P
HP
Claussen
C D
CD
Lang
F
F
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005682:Gadolinium / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
D005682:Gadolinium