Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress
Tp. Twaroski et al., Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress, BIOCH PHARM, 62(3), 2001, pp. 273-281
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.