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)
Muzi
G
G
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Gorski
J R
JR
Rozman
K
K
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