2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects vitamin a (vit a) homeostasis and kinetics in rats

Rats (n=14, liver VIT A = ∼2360 nmol) received weekly oral doses of corn oil (CN gp) or oil with TCDD (3.5 μg/kg BW, then 0.7 μg/kg weekly; TCDD gp). All rats received an IV dose of [³H]retinollabeled plasma 9 d after TCDD. Serial plasma samples were taken for 42 d, and urine and feces for 10 d. Plasma, liver, carcass, urine, and feces were analyzed for radioactivity, plasma and liver for VIT A. TCDD caused a 97% reduction in liver VIT A and a 20% increase in plasma retinol. VIT A balance was +33 (CN) and -21 nmol/d (TCDD) with intakes of ∼84 nmol/d. Recovery of tracer in urine and feces at 10 d was 3.7% and 23% in CN; values were 100% and 27% higher in TCDD. Using model-based compartmental analysis, a 4compartment model describing VIT A kinetics was developed. The site of dose and VIT A input was the plasma; output was from a slow turning-over extravascular compartment into a urine, fecal, or a third output pool. System residence time for VIT A was 36 (CN) vs. 15 d (TCDD). VIT A disposal rate was higher in TCDD (71 nmol/d) than CN (55 nmol/d). Output to the third pool was 2-fold higher in TCDD, perhaps reflecting an increase in water soluble VIT A metabolites in feces.