The neurotoxic effect of carbon disulphide, N-hexane and its metabolites studied with erythrocyte and synaptosome membranes in vitro.
The aim of the present study was to find a method for in vitro studies of the neurotoxic mechanism of industrial solvents. The effects of carbon disulphide and n-hexane and its metabolites were studied. Cell membrane changes were studied by measuring changes in the activity of the integral cell membrane enzymes acetylcholinesterase (AChE) and adenosinetriphosphatase (ATPase). The erythrocyte membranes were isolated from human peripheral blood samples and the synaptosome membranes from rat brain by using the non-toxic iso-osmotic Percoll gradient system. The cell membrane samples were incubated at +37 degrees C in an incubation mixture with known solvent concentrations. In erythrocyte membranes, n-hexane decreased the activity of AChE more than did carbon disulphide. In synaptosome membranes, 2-hexanone and 2,5-hexanedione inhibited AChE significantly more than did n-hexane. On ATPase, n-hexane, as well as the metabolites of n-hexane, had a slightly activating effect in erythrocyte membranes, and no or a slightly inactivating effect in synaptosome membranes. Carbon disulphide had a clear inactivating effect on ATPase in synaptosome membranes. The action of the neurotoxic organic solvents may be mediated by way of the integral membrane proteins, especially AChE. Thus, in neural synaptosome membranes, the metabolites of n-hexane had a greater effect on AChE activity than did n-hexane. The in vitro membrane model can be applied in studies of the neurotoxicity of organic solvents, and in predicting their neurotoxic potency.
Tähti
H
H
Department of Biomedical Sciences, University of Tampere, Box 607, SF-33101 Tampere, Finland.
Hyppönen
S
S