Higher toxicity of dibutyltin and poly-L-lactide with a large amount of tin but lower toxicity of poly-L-lactide of synthetic artificial dura mater exhibited on murine astrocyte cell line

Abstract

Neurotoxicities of dibutyltin (DBT), tin(II) octylate (OT), poly-L-lactides (PLLA, molecular weight [MW]= 5000, PLLA 5000), PLLA without tin (MW=3000, PLLA 3000), PLLA with a large amount (590 ppm) of tin (S3), poly(glycolic acid-co-ε-caprolactone) oligomer (MW=6200, PGC oligomer), and poly(L-lactic acid-co-glycolic acid-co-ε-caprolactone) oligomer (MW=6400, PLGC oligomer) related to artificial dura mater were examined using the murine astrocyte cell line, CRL-2534. The indices were cell viability, glutamate concentration in the cell supernatant, and cell proliferation. Lower cell viability was observed among cells exposed to 0.5 μM DBT or 10 μg/ml of S3. There were no differences in cell viability of astrocytes exposed to OT, PLLA 5000, PLLA 3000, PGC oligomer, or PLGC oligomer. Mean glutamate concentration in the supernatant of cells exposed to 0.25 μM DBT was higher than that of the control after 2 h incubation. Lower mean concentration of glutamate in the supernatant of cells exposed to 5 μg/ml of S3 was observed after 2 h incubation. Cells exposed to 50 μg/ml of PGC oligomer had a higher mean concentration of glutamate in the supernatant. OT only inhibited cell proliferation at 100 μM. Proliferation of cells exposed to 0.25 μM or 0.5 μM DBT was inhibited, as was that of cells exposed to 100 μM OT, 50 μg/ml PLLA 5000, 50 μg/ml PLLA 3000, and 5 μg/ml S3, 5 d and 7 d after exposure. Although DBT does not reach levels that induced neurotoxicity in artificial dura mater, these results suggest that DBT is neurotoxic and PLLA toxicity increases with the increase in tin concentration. © 2010 The Pharmaceutical Society of Japan.