Interaction between dietary vitamin A and single oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the TCDD-induced toxicity and on the vitamin A status in the rat.
The effect of dietary vitamin A on the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the effect of TCDD on the tissue vitamin A levels in 8-week-old male Sprague-Dawley rats of variable vitamin A status, were investigated. Rats were fed purified casein based diets containing 2,000, 5,000, 8,000, or 21,000 IU of vitamin A/kg from weaning and throughout the experiment. The study was terminated 44 days after the administration of a single oral dose of 0, 15, 30, 60, or 120 micrograms TCDD/kg body wt. With this dietary regimen it was possible to obtain healthy animals of the same age with a vitamin A status that varied within a physiological range. LD50-values for TCDD could not be calculated in any dietary group due to the unexpectedly low mortality rate. The obtained data, however, suggest that low dietary intake of vitamin A impairs the ability to tolerate the lethal effect of TCDD and/or decreases the survival time. Some TCDD-related effects, i.e. body weight loss, liver enlargement and decreased testes weight, were more pronounced in the groups receiving low levels of dietary vitamin A, whereas the decrease in thymus weight was as severe in all dietary groups. Exposure to TCDD had a pronounced effect on tissue vitamin A contents. The effect differed between tissues and was dependent upon the dose of TCDD and on the vitamin A status of the animal. Generally, exposure to TCDD results in the reduction of vitamin A in most organs; very likely because the capacity for vitamin A storage is diminished. The kidney is an exception because it accumulates vitamin A in response either to TCDD itself or to the altered vitamin A status which TCDD induces. Data presented in this study are not sufficient to conclude if the observed changes of tissue vitamin A contents are sufficient to explain the spectrum of morphological changes, which is typical of TCDD exposure.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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Håkansson
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Manzoor
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Ahlborg
D000818:Animals; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007928:Lethal Dose 50; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014801:Vitamin A / Q000008:administration & dosage* / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D014801:Vitamin A