> Persistent activation of the AhR is probably responsible for toxic
> responses in experimental animals and humans.
2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced oxidative stress in female
rats.
Oxidative stress may play a role in the toxic manifestations of
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Therefore, the time-
dependent effects of 100 micrograms TCDD/kg on various indices of
oxidative stress including lipid peroxidation. DNA damage, membrane
fluidity, calcium homeostasis, nonprotein sulfhydryl content, and
NADPH content of hepatic subcellular fractions of female rats were
followed for 12 days. Increases in lipid peroxidation of 400-500%
occurred in mitochondrial and microsomal membranes and nuclei, with
maximum increases occurring 5-6 days post-treatment. Decreases in the
nonprotein sulfhydryl content of mitochondrial and microsomal
fractions of approximately 80% were observed by Day 12 posttreatment.
Membrane fluidity gradually decreased following administration of
TCDD, with decreases of 30-40% being observed in mitochondria,
microsomes, and plasma membranes. A sharp increase in the incidence of
hepatic nuclear DNA single strand breaks was observed 3 days after
treatment with an increase of approximately 600% by Day 9. Following
the administration of TCDD, increases of 70-80% occurred in the
calcium content of mitochondria and microsomes. An 18% increase in
cytosolic calcium was present 12 days after the administration of
TCDD. Cytosol and mitochondria both exhibited an initial increase in
NADPH content following administration of TCDD, but by Day 12 both had
decreased to approximately two-thirds of control values. The results
clearly demonstrate that TCDD administration induces an oxidative
stress in rat liver. The most pronounced effects were observed in
membrane lipid peroxidation and DNA damage with gradual changes being
observed in calcium and nonprotein sulfhydryl contents and membrane
fluidity. PMID: 2251677
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