Marked alterations in retinoid homeostasis of Sprague-Dawley rats induced by a single i.p. dose of 10 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Interference of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in retinoid homeostasis was investigated in Sprague-Dawley rats with a low (dietary induced) retinoid status, that were fed a [3H]retinol-containing diet (37 MBq, 10,000 IU/kg diet) for 21 days to facilitate determination of retinoid concentrations in various tissues. The rats were exposed to a single i.p. dose of 10 micrograms TCDD/kg body weight in corn oil, or to corn oil at day 7 of [3H]retinol supplementation. TCDD induced significant reductions in retinol and retinyl ester concentrations and [3H] retinol-derived radioactivity in the liver, the lung, the intestine and the adrenals to 3-5%, 40-45%, 37%, and 56% of control values, respectively, at 14 days after exposure. In contrast, the retinoid concentrations and the amount of [3H]retinol-derived radioactivity in the kidney and serum of TCDD-treated rats was increased to 440% and 140% of corn oil-treated controls, respectively, at the termination time of the experiment. Analysis of the amount of serum retinol binding protein (RBP) by gel-permeation chromatography revealed an 150% increase in the free fraction of retinol-RBP, i.e., uncoupled to transthyretin (TTR), in serum of TCDD-treated rats. In addition, urinary excretion of [3H]retinol-derived radioactivity was significantly enhanced (to 140% of controls) by TCDD. These data indicate that TCDD induces an increased mobilization of retinoids from hepatic and extrahepatic storage sites into serum accompanied by an enhanced elimination via the kidney into the urine of rats.
Brouwer
A
A
Department of Toxicology, Agricultural University Wageningen, The Netherlands.
Håkansson
H
H
Kukler
A
A
Van den Berg
K J
KJ
Ahlborg
U G
UG
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011228:Prealbumin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012176:Retinoids / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011228:Prealbumin; D012176:Retinoids; D012177:Retinol-Binding Proteins; D014801:Vitamin A