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

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 (HpCD D) on brain serotonin metabolism, plasma tryptophan and liver tryptophan py rrolase 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 th at 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 a nd HpCDD. In contrast, to H/W rats HxCDD was the most toxic and TCDD the le ast 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 tryptoph an and plasma free tryptophan concentrations as well as for inhibition of t he main hepatic tryptophan metabolizing enzyme, tryptophan pyrrolase. By co ntrast, 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 c hanges in tryptophan homeostasis. These findings imply that in TCDD-suscept ible L-E and TCDD-resistant H/W rats the potency of dioxin congeners in ind ucing acute toxicity highly correlates with their ability to disrupt trypto phan homeostasis. However, there may not be a direct causal relationship be tween body weight loss and altered tryptophan homeostasis, because the magn itudes of these two phenomena were not consistently parallel across the dio xin congeners tested.