Effects of styrene and styrene oxide on glutathione-related antioxidant enzymes.

Styrene is both hepatotoxic and pneumotoxic in mice. Its mode of action is not clear, but it may be related to oxidative stress including a very large decrease in reduced glutathione (GSH). The current studies evaluated if: (1) the more toxic R-styrene oxide had a greater effect on reduced GSH levels than the less toxic S-styrene oxide, (2) the ratio of reduced to oxidized forms of glutathione was altered by styrene or styrene oxide, (3) other enzymes involved in the oxidant status of the cell, namely glutathione reductase, glutathione peroxidase and gamma-glutamylcysteine synthetase were altered, and (4) lipid peroxidation, as measured by the determination of malondialdehyde, increased. R-Styrene oxide (300mg/kg, ip) caused greater decreases in mouse liver and lung GSH than did S-styrene oxide (300mg/kg, ip). Styrene (600mg/kg, ip) caused decreases in both GSH and GSSG in both liver and lung. Styrene and styrene oxide did not cause significant increases in lipid peroxidation in either liver or lung. Styrene and styrene oxide had minimal effects on glutathione reductase and glutathione peroxidase in liver and lung. Styrene increased gamma-glutamylcysteine synthetase activity. The results suggest that while styrene and its metabolite styrene oxide cause significant decreases in GSH levels, they have little effect on the enzymes glutathione reductase and glutathione peroxidase and that in response to decreased glutathione levels there is an increase in its synthesis via induction of gamma-glutamylcysteine synthetase activity.