title: Cremophor EL, a non-ionic surfactant, promotes Ca(2+)-dependent process of cell death in rat thymocytes.
abstract: 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.
authors.affiliation: Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
authors.forename: Jun-Ya
authors.initials: JY
authors.lastname: Yamaguchi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Aimi
authors.initials: A
authors.lastname: Kanada
authors.forename: Masako
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Mishima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tatsuishi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Iwase
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oyama
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D007476:Ionophores; D013501:Surface-Active Agents; D000001:Calcimycin; C000515:cremophor EL; D004247:DNA; D006861:Hydrogen Peroxide; D005990:Glycerol; D002118:Calcium