Body weight loss and changes in tryptophan homeostasis by chlorinated dibenzo-p-dioxin congeners in the most TCDD-susceptible and the most TCDD-resistant rat strain

• Published in: Archives of toxicology 1998-12, Vol.72 (12), p.769-776
• Main Authors: UNKILA, M, POHJANVIRTA, R, TUOMISTO, J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Drug Resistance; Environmental pollutants toxicology; Female; General aspects; Homeostasis - drug effects; Medical sciences; Polychlorinated Dibenzodioxins - analogs & derivatives; Polychlorinated Dibenzodioxins - toxicity; Rats; Rats, Long-Evans; Rats, Wistar; Species Specificity; Toxicity Tests; Toxicology; Tryptophan - metabolism; Weight Loss - drug effects
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040050572

We compared the effects of 2,3,7,8-tetra (TCDD), 1,2,3,7,8-penta (PeCDD), 1,2,3,4,7,8-hexa (HxCDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) on brain serotonin metabolism, plasma tryptophan and liver tryptophan pyrrolase activity in two rat strains, TCDD-sensitive Long-Evans (Turku AB; L-E) and TCDD-resistant Han/Wistar (Kuopio; H/W). Previously it was shown that L-E rats exhibit the expected rank order of potency for CDDs in terms of acute toxicity with TCDD being the most potent, followed by PeCDD, HxCDD and HpCDD. In contrast, to H/W rats HxCDD was the most toxic and TCDD the least toxic of these congeners. In the present study, the CDDs decreased body weight in L-E rats in the following order of potency: TCDD > PeCDD > HxCDD > HpCDD. The same rank order was recorded for elevations in brain tryptophan and plasma free tryptophan concentrations as well as for inhibition of the main hepatic tryptophan metabolizing enzyme, tryptophan pyrrolase. By contrast, in H/W rats HxCDD was the most effective congener in producing loss of body weight, followed by HpCDD, PeCDD and TCDD. This was also true of changes in tryptophan homeostasis. These findings imply that in TCDD-susceptible L-E and TCDD-resistant H/W rats the potency of dioxin congeners in inducing acute toxicity highly correlates with their ability to disrupt tryptophan homeostasis. However, there may not be a direct causal relationship between body weight loss and altered tryptophan homeostasis, because the magnitudes of these two phenomena were not consistently parallel across the dioxin congeners tested.