Cremophor EL augments the cytotoxicity of hydrogen peroxide in lymphocytes dissociated from rat thymus glands.
The pharmaceutical uses of cremophor EL, a non-ionic surfactant, are similar to those of polysorbate 80. In our previous study, polysorbate 80 exerted some adverse actions on rat thymocytes under in vitro condition. Therefore, the effects of cremophor EL on thymic lymphocytes were examined using a flow cytometer with appropriate fluorescent dyes. Cremophor EL at 10 microg/ml or more (up to 300 microg/ml) concentration-dependently decreased cellular content of glutathione. The cell viability of thymocytes under control condition was 95.4 +/- 1.2% (n = 7, mean +/- S.D.). The incubation of thymocytes with 300 microg/ml cremophor EL or 3 mM hydrogen peroxide for 2 h, respectively, decreased the cell viability to 90.8 +/- 2.8% or 91.2 +/- 2.6%. However, the simultaneous incubation with cremophor EL and hydrogen peroxide decreased the cell viability to 28.7 +/- 8.2%. Cremophor EL at 100 microg/ml accelerated the process of cell death induced by hydrogen peroxide. Results suggest that cremophor EL increases the susceptibility to oxidative stress. Cremophor EL at clinically relevant concentrations may increase the therapeutic potential of some anticancer agents to produce oxidative stress.
Laboratory of Cell Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
Kyoko
K
Iwase
Yasuo
Y
Oyama
Tomoko
T
Tatsuishi
Jun-ya
JY
Yamaguchi
Yumiko
Y
Nishimura
Aimi
A
Kanada
Masako
M
Kobayashi
Yuko
Y
Maemura
Shiro
S
Ishida
Yoshiro
Y
Okano
D000818:Animals; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D006861:Hydrogen Peroxide; D005978:Glutathione; D005990:Glycerol