Lead cytotoxicity in primary cultured rat astrocytes and Schwann cells.

Abstract

The cytotoxic effects of lead acetate on primary cultured astrocytes and Schwann cells (SCs) were studied for comparing the sensitivity of the two kinds of cells and exploring the possible mechanism of lead cytotoxicity. The results indicated that the number of astrocytes detached from the culture surfaces were dependent on the concentration and time of lead exposure. Under phase contrast microscopy, increases in the number of vacuoles were observed at doses of 50 and 100 micrograms ml-1 lead after 96 h of lead exposure for astrocytes and 1, 5 and 10 micrograms ml-1 lead after 24 h of lead exposure for SCs. By scanning electron microscopy, the surface changes in astrocytes began to appear at the dose of 10 micrograms ml-1 lead, whereas in SCs it began in 1 microgram ml-1 lead. By transmission electron microscopy, astrocytes exposed to 10, 50 and 100 micrograms ml-1 lead had increased lysosomal densities, the presence of nuclear inclusions and enlargement of rough endoplasmic reticulum, whereas SCs exposed to 1 microgram ml-1 lead began to show swelling of mitochondria and endoplasmic reticulum, cytoplasmic vacuolizations and numerous myelinoid bodies. Increases in the content of lactic dehydrogenase (LDH) leakage from the astrocytes exposed to 100 micrograms ml-1 lead and SCs exposed to 1, 5 and 10 micrograms ml-1 lead were observed, respectively. Decreases in sulphydryl group (SH) levels in astrocytes exposed to 50 and 100 micrograms ml-1 lead and SCs exposed to 1, 5 and 10 micrograms ml-1 lead were also observed. A dose of 1.0 mmol l-1 reduced glutathione (GSH) and 2.0 mmol l-1 dithiothreitol (DTT) could protect astrocytes from lead-induced SH decrease and LDH leakage. Doses of 10-100 mumol l-1 cAMP were shown to have a protective effect on lead-induced SH decrease in SCs. No significant changes of GSH or lipid peroxidation (LPO) were observed in astrocytes. The results indicated that SH was involved in lead-induced cytotoxicity of astrocytes and SCs, and SCs were more sensitive to lead-induced cytotoxicity than astrocytes.