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 micrograms/kg) in cold-adapted (4 +/- 1 degrees 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 pair-fed 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 pair-fed 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
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Muzi
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Gorski
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Rozman
D000064:Acclimatization; D000818:Animals; D003080:Cold Temperature; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D004147:Dioxins / Q000633:toxicity*; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000097:blood
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones