Comparison of the depletion of glutathione in mouse liver and lung following administration of styrene and its metabolites styrene oxide and 4-vinylphenol

Styrene is hepatotoxic and pneumotoxic in mice. Its major metabolite styrene oxide and its minor, but potent, metabolite 4-vinylphenol cause similar toxicities. Styrene and styrene oxide cause decreases in reduced glutathione levels in tissues. The current studies examined styrene and styrene oxide in a time and dose-dependent manner and 4-vinylphenol in a time dependent fashion. Styrene (600 mg/kg, 5.8 mmol/kg ip) caused decreased GSH levels in both liver and lung within one hour. A maximum was seen at three hours with return to control levels by 12 h. Lower doses also caused changes in a dose-dependent fashion. For styrene oxide, similar findings were observed with a dose of 300 mg/kg (2.5 mmol/kg). GSH levels in liver, but not lung, returned to control by 6 h. Again a dose response was found for both tissues. While 4-vinylphenol (100 mg/kg, 0.83 mmol/kg) was administered at a dose known to be more hepatotoxic and more pneumotoxic than styrene or styrene oxide and it caused decreased GSH levels, the degree of depletion was less compared to styrene and styrene oxide. In general the lung was more affected by these agents than was liver. The decreases in GSH suggest the possibility that the toxicity of styrene in lung and liver may be related to a profound but reversible oxidative stress in these tissues.