Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult (5-month-old) and aged (14-month-old) rats. Depression of levels of glutamine synthetase in the P2 fraction of kidney was observed, which was more severe in aged than young adult rats. Glutamine synthetase is a cytosolic enzyme especially susceptible to oxidative damage. A parallel depression of this enzyme was also seen in the corresponding hepatic fractions. However, levels of glutamine synthetase in the hippocampus were elevated by this exposure. Glutathione levels were depressed in P2 fractions of livers of exposed rats, and also in the corresponding renal fraction. Glutathione concentration was unchanged in cerebral fractions. Overall results were interpreted to imply that pro-oxidant events were elevated in kidney and liver following prolonged inhalation of the solvent mixture. The changes found in brain tissue did not reveal evidence of oxidative stress but, however, suggested that glial activation was taking place.

The present study was undertaken in order to investigate whether dearomatized white spirit induces indices of oxidative stress in subcellular fractions of hemisphere, hippocampus, kidney and liver tissue of rats exposed to 0, 400 and 800 ppm 6 hr/day, 7 days a week for 3 weeks. The results show that white spirit is a strong in vivo inducer of oxidative stress in subcellular fractions of brain, kidney and liver. In the liver there was a statistically significant increase in the rate of reactive oxygen species (ROS) generation and a decrease in glutamine synthetase activity. In the kidney there was a statistically significant decrease in the rate of ROS generation. In the hemisphere there was a statistically significant increase in the level of reduced glutathione. In the hippocampus there was a statistically significant increase in the rate of ROS generation. However, in vitro addition of dearomatized white spirit had no effect on the rate of cerebrocortical P2 fraction ROS generation. The results suggest that cumulative oxidative damage may be an underlying mechanism of dearomatized white spirit-induced neurotoxicity and that various regions of the brain may respond differently.