Hepatic vitamin A depletion is a sensitive marker of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in four rodent species

被引:47
作者
Fletcher, N [1 ]
Hanberg, A [1 ]
Håkansson, H [1 ]
机构
[1] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden
关键词
2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; vitamin A; retinoids; wasting; EROD; species; hepatic; renal;
D O I
10.1093/toxsci/62.1.166
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-treated animals show altered retinoid homeostasis and exhibit signs of toxicity similar to those of vitamin A-deficient animals. In this study we established dose-response curves for sublethal oral doses of TCDD and hepatic vitamin A gain in four rodent species. This was done to evaluate any potential correlation between decreased hepatic vitamin A gain and other TCDD-induced effects, particularly depressed body weight gain and hepatic CYP1A induction. Young Hartley guinea pigs, Sprague-Dawley rats, C57BL16 mice, and Golden Syrian hamsters were given single oral doses of TCDD at up to 2.5, 100, 1000, and 1000 mug/kg bw, respectively, and killed 28 days after treatment. Hepatic vitamin A gain was decreased 25% compared to controls at estimated doses of 0.1, 0.9, 1.1 and 3.6 mug/kg bw in guinea pigs, hamsters, rats, and mice, respectively. CYP1A induction and hepatic vitamin A gain were affected at similar dose levels and showed similar, but inverse dose-response curves in each of the four species, consistent with the hypothesis that altered vitamin A homeostasis is Ah-receptor mediated. In addition, there was an apparent correlation between the dose-response curves for decreased hepatic vitamin A gain and decreased body weight gain in all species. Taken together with the known importance of vitamin A in body weight regulation, this result was consistent with a contributing role for altered retinoid homeostasis in the wasting syndrome induced by TCDD.
引用
收藏
页码:166 / 175
页数:10
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