Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and disturbance of intermediary metabolism in the Long-Evans rat.
The aim of this study was to examine the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin, (TCDD) in a rat strain other than the Sprague-Dawley (S-D) rat, for which most of our data have been generated thus far. Doses for the biochemical study were selected based on an acute range-finding study, which indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67, 100 and 150 micrograms/kg TCDD. Body weight and feed intake were dose-dependently decreased prior to killing of the animals. Eight days after dosing, animals were killed and tryptophan, total T4 (TT4) and total T3 (TT3) levels were determined in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD), phosphoenolpyruvate carboxykinase (PEPCK), gamma-glutamyl transpeptidase (gamma-GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity was fully induced at all doses studied, indicating that as in S-D rats, Ah-receptor-mediated effects do not seem to play any major role in the acute toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose-dependently decreased in a similar dose range as in S-D rats, indicating inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a result of a dose-dependent elevation in serum tryptophan levels, which in turn were related to reduced liver TdO activity. Hepatic gamma-GT activity was also dose-dependently reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Rozman
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014364:Tryptophan / Q000097:blood / Q000187:drug effects; D014366:Tryptophan Oxygenase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D005723:gamma-Glutamyltransferase