Effect of thimerosal, a preservative in vaccines, on intracellular Ca2+ concentration of rat cerebellar neurons.
The effect of thimerosal, an organomercurial preservative in vaccines, on cerebellar neurons dissociated from 2-week-old rats was compared with those of methylmercury using a flow cytometer with appropriate fluorescent dyes. Thimerosal and methylmercury at concentrations ranging from 0.3 to 10 microM increased the intracellular concentration of Ca2+ ([Ca2+]i) in a concentration-dependent manner. The potency of 10 microM thimerosal to increase the [Ca2+]i was less than that of 10 microM methylmercury. Their effects on the [Ca2+]i were greatly attenuated, but not completely suppressed, under external Ca(2+)-free condition, suggesting a possibility that both agents increase membrane Ca2+ permeability and release Ca2+ from intracellular calcium stores. The effect of 10 microM thimerosal was not affected by simultaneous application of 30 microM L-cysteine whereas that of 10 microM methylmercury was significantly suppressed. The potency of thimerosal was similar to that of methylmercury in the presence of L-cysteine. Both agents at 1 microM or more similarly decreased the cellular content of glutathione in a concentration-dependent manner, suggesting an increase in oxidative stress. Results indicate that thimerosal exerts some cytotoxic actions on cerebellar granule neurons dissociated from 2-week-old rats and its potency is almost similar to that of methylmercury.
Ueha-Ishibashi
Toshiko
T
Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
Oyama
Yasuo
Y
Nakao
Hiromi
H
Umebayashi
Chisato
C
Nishizaki
Yasutaka
Y
Tatsuishi
Tomoko
T
Iwase
Kyoko
K
Murao
Koji
K
Seo
Hakaru
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D008767:Methylmercury Compounds / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013849:Thimerosal / Q000633:toxicity*; D014612:Vaccines / Q000737:chemistry*
D005456:Fluorescent Dyes; D008767:Methylmercury Compounds; D011310:Preservatives, Pharmaceutical; D014612:Vaccines; D013849:Thimerosal; D002118:Calcium