Differential regulation of hepatic glutathione transferase and glutathione peroxidase activities in the rat

Abstract

The effects of the xenobiotics, i.e. butylated hydroxytoluene, beta-naphthoflavone, isosafrole, pregnenolone-16 alpha-carbonitrile, trans-stilbene oxide, 3-methylcholanthrene, phenobarbital, 3,3',4,4'-tetrachlorobiphenyl, 2,2',4,4',5,5'-hexachlorobiphenyl, on rat liver cytosolic glutathione transferase and glutathione peroxidase activities have been investigated. Although the glutathione transferase isozymes (measured by the specific substrates ethacrynic acid and delta 5-androstene-3,17-dione) which have been shown to possess peroxidase activity were significantly increased, little or no increase in peroxidase activity (toward cumene hydroperoxide, tert-butyl hydroperoxide or hydrogen peroxide) was observed. Likewise during a 16-day time course following the administration of Aroclor 1254 or fireMaster BP-6 (each 500 mg/kg, i.p.), potent induction of glutathione transferase activities was seen without any significant increases in peroxidase activities. In fact during the second week of the time course, there were significant decreases in selenium-dependent glutathione peroxidase activity (toward hydrogen peroxide). The inverse regulation of these activities, i.e. the depression of selenium-dependent glutathione peroxidase activity following sustained induction of glutathione transferases, may have direct implications for the toxicity of the polyhalogenated aromatic hydrocarbons.