A rapid screening method to test apoptotic synergisms of ochratoxin A with other nephrotoxic substances.
The body may be exposed simultaneously to more than one nephrotoxic substance and to measure the effects of the great number of possible combinations of nephrotoxins will rapidly become a great challenge when using the traditional methods. Therefore, we developed a rapid and cost-efficient method to screen the apoptotic potential of combinations of known cell- or nephrotoxic substances as ochratoxin A (OTA), cisplatin, cadmium, H(2)O(2), and amphotericin B on renal epithelial cell lines. The cells were seeded in 96-well plates and the apoptotic and necrotic potential of different combinations of nephrotoxins was determined. We found different results for the combinations used: depending on the concentrations of the various substances, antagonistic, additive, or potentiating effects on caspase-3 activity were found after co-exposure to OTA. We conclude that the co-exposure of renal cells to OTA with other substances can enhance or reduce the apoptotic potential of one substance alone depending on the substance, the concentration and on the cell line investigated. A "harmless" substance can thus convert to a potent cell toxic substance when combined with OTA or vice versa. The underlying mechanisms of the synergistic effects remain unknown.
Weber
Florian
F
Physiologisches Institut, Universität Würzburg, Röntgenring 9, D-97070 Würzburg, Germany.
Freudinger
Ruth
R
Schwerdt
Gerald
G
Gekle
Michael
M
D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009183:Mycotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D018675:Toxicity Tests / Q000191:economics / Q000379:methods*; D014343:Trypan Blue / Q000378:metabolism
D004338:Drug Combinations; D009183:Mycotoxins; D009793:Ochratoxins; D011506:Proteins; D002104:Cadmium; C025589:ochratoxin A; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D014343:Trypan Blue; D002945:Cisplatin