Composition of diet modifies toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in cold-adapted rats

The effect of a high carbohydrate, high fat or high protein diet was studied on the acute toxicity of TCDD (125 g/kg) in cold-adapted (4±1° C) rats. Within 10 days after dosing, TCDD-treated rats fed a high carbohydrate or a high protein diet reduced their caloric intake by 25% whereas those fed a high fat diet consumed only 15% fewer kcal/MBS (metabolic body size). TCDD-treated rats fed a high protein diet lost body weight at the same rate as their pair-fed controls, whereas body weight loss in high fat-fed rats was significantly higher than in their pairfed controls. In contrast, TCDD-treated rats fed a high carbohydrate diet effectively maintained their body weight in the 4 days immediately after TCDD dosage, whereas their pair-fed controls lost weight. Mortality in TCDD-treated animals was 100% irrespective of the diet; all pairfed control rats (except one fed a high protein diet) were terminated on days corresponding to the spontaneous death of their TCDD-treated pairs. Mean time to 50% mortality and mean time to death were significantly longer in TCDD-treated rats fed a high carbohydrate diet in comparison with the other two TCDD-treated groups (p<0.05), although caloric intake was comparable. Serum triiodothyronine (T₃) was reduced in TCDD-treated animals fed a high fat or a high carbohydrate diet but not in those fed a high protein diet; serum thyroxine (T₄) was reduced in all the treated groups, irrespective of diet. The relative weight of liver was significantly higher in all TCDD-treated animals; the weight of pancreas was higher only in high carbohydrate-fed TCDD-treated rats and the weight of interscapular brown adipose tissue was lower only in high fat-fed TCDD-treated rats in comparison to pair-fed controls. It is concluded that TCDD-treated cold-adapted rats utilize carbohydrate and fat differently than pair-fed controls and that these changes probably contribute to the development of a wasting syndrome.This work was supported in part by a grant from the Bayerisches Staatsministerium für Landesentwicklung und Umweltfragen, München (Fed. Republic of Germany)