Dose response and time course of alterations in tryptophan metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the most TCDD-susceptible and the most TCDD-resistant rat strain: relationship with TCDD lethality

Toxicology and Applied Pharmacology
M UnkilaJ Tuomisto

Abstract

It has previously been shown that an increase in plasma free tryptophan and a consequent increase in brain serotonin (5-HT) metabolism may be associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality. In the present study we have studied the dose-response and time course relationships of these phenomena in the most TCDD-susceptible Long-Evans (Turku AB [L-E]; LD50 ca. 10 micrograms/kg) and the most TCDD-resistant Han/Wistar (Kuopio [H/W], LD50 > 7200 micrograms/kg) rat strains. Six days after exposure, there was a dose-related increase in brain 5-HT turnover and plasma free tryptophan in both male and female L-E rats. Pair-fed control rats did not exhibit changes in these parameters. The increases emerged in the dose range known to elicit lethality in L-E rats. Furthermore, the increases in plasma free tryptophan correlated well with the changes in body weight caused by TCDD. In contrast, in H/W rats no such increases in brain 5-HT metabolism or plasma free tryptophan were discernible. Similarly, body weight changes were minor in H/W rats despite almost 1000-fold greater doses of TCDD. Large neutral amino acids other than tryptophan were not markedly changed in the plasma of either rat strain. In attempts to identify...Continue Reading

Citations

Nov 22, 2012·RNA·Stephenie D ProkopecPaul C Boutros
Apr 10, 2003·Biochemical and Biophysical Research Communications·Merja KorkalainenRaimo Pohjanvirta
May 9, 2012·Toxicology and Applied Pharmacology·Raimo PohjanvirtaJere Lindén
Feb 22, 2012·Toxicology and Applied Pharmacology·Cindy Q YaoPaul C Boutros
Dec 21, 2013·Toxicology and Applied Pharmacology·John D WatsonPaul C Boutros
Jul 6, 2005·Toxicology and Applied Pharmacology·Jouko Tuomisto
Nov 20, 2018·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Laurentius Ron Hoogenboom
Jun 26, 2001·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·B StantonB Lasley
May 1, 1995·The International Journal of Biochemistry & Cell Biology·M UnkilaJ Tuomisto

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