title: Flow-cytometric analysis on adverse effects of polysorbate 80 in rat thymocytes.
abstract: The effects of polysorbate 80, a non-ionic surfactant widely used in pharmaceutical products, on rat thymocytes were examined to reveal its toxic property at the cellular level. Polysorbate 80 at concentrations of 1-100 microg/ml did not significantly affect the cell viability. This surfactant at 30 microg/ml or more augmented the intensity of fluo-3 fluorescence, indicating the increase in intracellular Ca(2+) concentration. Such an augmentation of fluo-3 fluorescence by polysorbate 80 was not seen under the Ca(2+)-free condition, suggesting that polysorbate 80 increased membrane Ca(2+) permeability. The concentration-dependent polysorbate 80 at 10 microg/ml or more attenuated the intensity of 5-chloromethylfluorescein, indicating a decrease in cellular content of glutathione by polysorbate 80. Furthermore, the agent at 1 microg/ml or more attenuated the intensity of bis-(1,3-dibutylbarbituric acid) trimethine oxonol fluorescence, being independent from the changes in membrane potential. This phenomenon indicates that polysorbate 80 at 1 microg/ml or more may attenuate the incorporation of anionic compounds into the membranes. It can be suggested that polysorbate 80 modifies some of membranes and intracellular physiological parameters without affecting the cell viability.
authors.affiliation: Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Hirama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tatsuishi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Iwase
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakao
authors.forename: Chisato
authors.initials: C
authors.lastname: Umebayashi
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: Masako
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ishida
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oyama
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods*; D005978:Glutathione / Q000378:metabolism; D011136:Polysorbates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D011136:Polysorbates; D013501:Surface-Active Agents; D005978:Glutathione; D002118:Calcium