Property of thimerosal-induced decrease in cellular content of glutathione in rat thymocytes: a flow cytometric study with 5-chloromethylfluorescein diacetate.
There is a concern on the part of public health community that adverse health consequences by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the effect of thimerosal on cellular content of glutathione was examined on thymocytes obtained from 4-week-old rats using a flow cytometer and 5-chloromethylfluorescein diacetate. Thimerosal at concentrations ranging from 1 to 10 microM reduced the cellular content of glutathione in a concentration-dependent manner, and the complete depletion of cellular glutathione was observed when the cells were treated with 30 microM thimerosal. L-Cysteine significantly attenuated the actions of thimerosal to reduce the glutathione content and to increase the intracellular Ca2+ concentration. Prolonged incubation (24 h) with 1-3 microM thimerosal induced the apoptosis. The cytotoxic action of thimerosal was greatly augmented when the cells suffered oxidative stress induced by H2O2. It may be unlikely that thimerosal exerts potent cytotoxic action under the in vivo condition because the blood concentration of thimerosal after receiving vaccines does not seem to reach micromolar range and nonprotein thiols at micromolar concentrations are present in the blood.
Ueha-Ishibashi
T
T
Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Minami-Jyosanjima 1-1, Tokushima 770-8502, Japan.
Tatsuishi
T
T
Iwase
K
K
Nakao
H
H
Umebayashi
C
C
Nishizaki
Y
Y
Nishimura
Y
Y
Oyama
Y
Y
Hirama
S
S
Okano
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005434:Flow Cytometry / Q000379:methods*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013849:Thimerosal / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D004338:Drug Combinations; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011310:Preservatives, Pharmaceutical; C069306:5-chloromethylfluorescein; D013849:Thimerosal; D006861:Hydrogen Peroxide; D005978:Glutathione