Cremophor EL, a non-ionic surfactant, promotes Ca(2+)-dependent process of cell death in rat thymocytes.
Cremophor EL, a surfactant for pharmaceutical products, augments the cytotoxicity of hydrogen peroxide in rat thymocytes [Iwase, K., Oyama, Y., Tatsuishi, T., Yamaguchi1, J., Nishimura1, Y., Kanada, A., Kobayashi, M., Maemura, Y., Ishida, S., Okano, Y., 2004. Cremophor EL augments the cytotoxicity of hydrogen peroxide in lymphocytes dissociated from rat thymus glands. Toxicol. Lett. 154, 143-148]. The effect of cremophor EL on Ca(2+)-dependent process of cell death has been examined using a flow cytometer since hydrogen peroxide increases intracellular Ca2+ concentration. Cremophor EL at clinically-relevant concentrations greatly increased the population of dead cells in rat thymocytes simultaneously treated with A23187, a calcium ionophore increasing intracellular Ca2+ concentration. Removal of Ca2+ from external solution diminished the cremophor EL-induced increase in the dead cell population. Result suggests that Ca(2+)-dependent process is involved in the cremophor EL-induced decrease in the cell viability in the simultaneous presence of A23187. The population of cells with hypodiploidal DNA was not increased by the application of cremophor EL and A23187 although the cell viability was greatly decreased, indicating that the type of cell death is necrosis. It is suggested that cremophor EL at clinically-relevant concentrations augments the Ca(2+)-dependent process of necrosis.
Yamaguchi
Jun-Ya
JY
Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
Nishimura
Yumiko
Y
Kanada
Aimi
A
Kobayashi
Masako
M
Mishima
Kyoko
K
Tatsuishi
Tomoko
T
Iwase
Kyoko
K
Oyama
Yasuo
Y
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005990:Glycerol / Q000031:analogs & derivatives* / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000633:toxicity*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007476:Ionophores; D013501:Surface-Active Agents; D000001:Calcimycin; C000515:cremophor EL; D004247:DNA; D006861:Hydrogen Peroxide; D005990:Glycerol; D002118:Calcium