Sub-chronic effects of styrene and styrene oxide on lipid peroxidation and the metabolism of glutathione in rat liver and brain.

Sub-chronic effects of styrene and styrene oxide on lipid peroxidation, glutathione contents and glutathione reductase activities in the liver and brain were examined after intraperitoneal administration to rats 3 times a week for 7 weeks. Styrene (300, 400 and 500 mg/kg) and styrene oxide (200 and 300 mg/kg) increased lipid peroxidation in the liver after 7 weeks of treatment. Hepatic lipid peroxidation in the rats treated with a higher dose of styrene oxide (400 mg/kg) was significantly enhanced even after 2 weeks of treatment. On the other hand, no change in lipid peroxidation was observed in the brain under the above conditions. Neither glutathione contents nor glutathione reductase activities in the liver and brain were altered at 40 h after the last of these sub-chronic treatments. To elucidate the cause of lipid peroxidation, the time courses of glutathione content after treatment with either styrene or styrene oxide (300 mg/kg) were studied in more detail. Significant decreases in both the GSH and GSSG contents were detected shortly after these treatments and the levels recovered to the control values at 40 h in these organs, although the changes were less significant in the brain of rats treated with styrene. These results suggest that enhancement of lipid peroxidation in the liver after treatment with styrene or styrene oxide was a consequence of repeated depletions of glutathione to certain critical levels and delayed recovery of lipid peroxides.