Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress

Polychlorinated biphenyls (PCBs) induce drug metabolism that may lead to th e bioactivation of PCBs themselves or alternatively may lead to oxidative e vents within the cell. The goal of the present study was to determine the i nfluence of congeneric PCBs, selected as substrates for or inducers of drug metabolism, upon hepatic glutathione, glutathione-related enzymes, and sel enium status. Male and female Sprague-Dawley rats received two i.p, injecti ons per week of PCB 3 (4-chlorobiphenyl), PCB 28 (2,4,4'-trichlorobiphenyl) , PCB 38 (3,4,5-trichlorobiphenyl), PCB 77 (3,3',4,4'-tetrachlorobiphenyl), PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), or both PCBs 77 and 153 (100 mu mol/kg/injection) and were killed at the end of 1, 2, or 3 weeks. Whole liver homogenates, hepatic cytosol, and microsomes were prepared. Both glut athione reductase and glutathione transferase activities were increased sig nificantly in both male and female rats receiving PCB 77, an aryl hydrocarb on receptor agonist, as well as in those receiving both PCBs 77 and 153. No significant trend was observed in the levels of hepatic total glutathione. PCB 77 treatment decreased hepatic selenium-dependent glutathione peroxida se (SeGPX) activity in both male and female rats significantly. This decrea se in activity following PCB 77 treatment was accompanied by a decrease in the cytosolic selenium-dependent glutathione peroxidase gene (GSPx1) transc ript, as well as a decrease in hepatic total selenium levels. These data su pport the concept that exposure to the coplanar PCB 77 suppresses, via gene regulatory mechanisms, the cellular antioxidant enzyme SeGPX and that this decrease involves selenium. Lower halogenated PCBs that may be bioactivate d to reactive oxygen species (ROS)-producing metabolites, and higher haloge nated PCBs that are not Ah receptor agonists, were inactive. (C) 2001 Elsev ier Science Inc. All rights reserved.