Glutathione peroxidase and reactive oxygen species in TCDD-induced lipid peroxidation.
Previous studies have shown that high doses of TCDD induce hepatic lipid peroxidation and inhibit selenium dependent glutathione peroxidase (GSH-Px) activity. The dose dependent effects of TCDD on hepatic lipid peroxidation (malondialdehyde content) and GSH-Px activity were determined. A dose as low as 1 microgram/kg induced hepatic lipid peroxidation and inhibited GSH-Px. Based on the use of scavengers of reactive oxygen species, lipid peroxidation (malondialdehyde formation) by hepatic microsomes from both control and TCDD-treated rats appears to be due primarily to H2O2. The results indicate that superoxide, hydroxyl radical and singlet oxygen are also involved. The differences in the reactive oxygen species involved in microsomal lipid peroxidation between control and TCDD treated animals appear to be quantitative rather than qualitative. A 5.9-fold greater rate of malondialdehyde (MDA) formation by microsomes from TCDD treated animals occurred as compared to controls, while livers of TCDD rats had an MDA content that was 5.0-fold greater than the controls. These differences may be due in part to an enhanced production of H2O2 as well as a decrease in the activity of selenium dependent glutathione peroxidase which metabolizes H2O2.
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism
D004147:Dioxins; D006878:Hydroxides; D008054:Lipid Peroxides; D008314:Malonates; D000072317:Polychlorinated Dibenzodioxins; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase