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Effects of vitamin A and/or thyroidectomy on liver microsomal enzymes and their induction in 2,3,7,8-tetrachlorodibenzo- p -dioxin-treated rats

Toxicology, ISSN: 0300-483X, Vol: 46, Issue: 1, Page: 107-117
1987
  • 14
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  • 8
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Metrics Details

  • Citations
    14
    • Citation Indexes
      12
    • Policy Citations
      2
      • 2
  • Captures
    8

Article Description

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 T 3 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 (T 4 ) and triiodothyronine (T 3 ) levels, although the levels of T 3 remained in the euthyroid range (60–80 ng/dl). The concentration of liver microsomal cytochromes P -450 and b 5 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 T 3 than on T 4 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 T 3. 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 T 4. 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.

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