Short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Long-Evans rats.
The aim of this study was to examine short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Long-Evans (L-E) rats. In the short-term study, female rats were dosed orally with 5.3, 12, 18 and 60 micrograms TCDD/kg and sacrificed 4 days after dosing. In the long-term study, rats were dosed with 27, 40 and 60 micrograms TCDD/kg and sacrificed 90 days after dosing. Four days after dosing, ethoxyresorufin O-deethylase (EROD) activity was fully induced at all doses studied, hepatic phosphoenolpyruvate carboxykinase (PEPCK) and gamma-glutamyl transpeptidase (gamma-GT) activities were dose-dependently reduced, whereas hepatic tryptophan 2,3-dioxygenase (TdO) activity was stimulated at low doses but decreased at high doses. Serum total T4 (TT4) levels were dose-dependently decreased, whereas serum total T3 (TT3) and tryptophan levels were unaffected. The short-term effects of TCDD examined in this study indicate only small differences in the response of female L-E rats to TCDD as compared to males. Ninety days after dosing, liver EROD activity revealed considerable reversibility although it was still elevated compared to controls. Hepatic PEPCK activity at this time point was no more different from controls. In contrast to 4 days after dosing, serum TT3, TT4 and hepatic gamma-GT activity were dose-dependently elevated at the 90-day time point. These findings have significant implications for the interpretations of subchronic and chronic effects of TCDD on thyroid homeostasis and on the formation of preneoplastic liver foci.
Fan
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Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City.
Rozman
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D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D013974:Thyroxine / Q000187:drug effects; D014284:Triiodothyronine / Q000187:drug effects; D014364:Tryptophan / Q000097:blood; D014366:Tryptophan Oxygenase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D014284:Triiodothyronine; D014364:Tryptophan; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D014366:Tryptophan Oxygenase; D019363:Cytochrome P-450 CYP1A1; D005723:gamma-Glutamyltransferase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D013974:Thyroxine