Biotransformation of carbon tetrachloride in cultured neurons and astrocytes

Abstract

The ability of brain neuronal cells to metabolize carbon tetrachloride (CCl 4) has been studied in an attempt to explain earlier observed toxic effects of CCl 4 on these cells. The expression of cytochrome P-450, the glutathione (GSH) content and the activity of glutathione- S-transferase (GST) were measured in cultured neurons and astrocytes from chick embryo cerebral hemispheres. The metabolism of CCl 4 in the neuron and astrocyte cultures was also assessed by determining the formation of: CCl 2 in membrane preparations of these cells. In the membrane fractions of neurons and astrocytes, no measurable levels of cytochrome P-450 were observed. Nevertheless, neurons as well as astrocytes had a capacity for the metabolism of CCl 4. The metabolic capacity of the neurons was significantly greater than that of the astrocytes. The neuron cultures had a higher initial content of GSH and a higher control activity of GST than had the astrocytes. Neither the GSH level nor GST activity were significantly affected in the neuron cultures after exposure to CCl 4. In astrocyte cultures 2 m m CCl 4 slightly depleted the GSH level and significantly induced GST activity. At 3 m m CCl 4, GSH was depleted by 30% and by more than 50% at 4 m m CCl 4. It can be concluded that the metabolic activation of CCl 4 was higher in neurons than in astrocytes. This can explain the earlier observation of CCl 4-induced lipid peroxidation in cultured neurons. Moreover, neuron GSH was not able to protect these cells against CCl 4-induced peroxidative damage. In the astrocytes, on the other hand, GSH and GST appeared to have a role in detoxification of CCl 4.