Effects of vitamin A and/or thyroidectomy on liver microsomal enzymes and their induction in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.
Vitamin A and thyroid hormone status have been shown previously to alter the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats. In the present study, we have examined the effects of a vitamin A-excess and a vitamin A-deficient diet on thyroid hormone levels, on selected drug-metabolizing enzymes in liver microsomes, and on their inducibility by TCDD in male Sprague-Dawley rats. Except for a slight increase in serum T3 levels, none of these end points was affected by feeding rats the vitamin A-deficient diet. In contrast, excess dietary vitamin A caused a decrease in serum thyroxine (T4) and triiodothyronine (T3) levels, although the levels of T3 remained in the euthyroid range (60-80 ng/dl). The concentration of liver microsomal cytochromes P-450 and b5 and the basal activity of benzo[a]pyrene hydroxylase and 7-ethoxyresorufin O-de-ethylase were unaffected by excess dietary vitamin A. This result is consistent with our previous observation that the basal activity of these enzymes is dependent more on T3 than on T4 levels. Vitamin A excess markedly suppressed the activity of liver microsomal UDP-glucuronosyl transferase toward 1-naphthol. However, no such enzyme suppression was observed in thyroidectomized rats. This suggests that the suppressive effect of vitamin A on UDP-glucuronosyl transferase activity may be dependent on T3. Neither vitamin A nor thyroid status had any major effect on the inducibility of UDP-glucuronosyl transferase and cytochrome P-450-dependent enzyme activities by TCDD. However, vitamin A and TCDD had a nearly additive effect on suppression of serum T4. It is concluded that liver microsomal enzyme induction is not associated with the modulatory effect of vitamin A and thyroid hormones on the toxicity of TCDD.
D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004147:Dioxins / Q000633:toxicity*; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000032:analysis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D013965:Thyroidectomy; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*; D014801:Vitamin A / Q000494:pharmacology*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D014284:Triiodothyronine; D014801:Vitamin A; D001579:Benzopyrene Hydroxylase; D014453:Glucuronosyltransferase; D013974:Thyroxine