> salicylamide is an antagonist of the aryl hydrocarbon ...
Inhibitory effects of vitamin A on TCDD-induced cytochrome P-450 1A1
enzyme activity and expression.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potent
environmental contaminant that produces a wide range of adverse
biological effects, including the induction of cytochrome P450
1A1(CYP1A1) that may enhance the toxic effects of TCDD. Several
studies indicated that concurrent supplementation of vitamin A could
reduce the toxicity, and potentially inhibit CYP1A1 activity (measured
as ethoxyresorufin-O-deethylase [EROD] activity). In the present
study, we investigated the in vivo effects of vitamin A on EROD
activities and the expression of CYP1A1 in the liver of TCDD-treated
mice. In Experiment I, the mice were given a single oral dose of 40
mug TCDD/kg body weight with or without the continuous administration
of 2500 IU vitamin A/kg body weight/day, and were killed on day 1, 3,
7, 14, or 28. In Experiment II, the mice were given daily an oral dose
of 0.1 mug TCDD/kg body weight with or without supplement of 2000 IU
vitamin A/kg body weight, and were killed on day 14, 28, or 42. In
both experiments, TCDD caused liver damage and increase in relative
liver weights, augmented the EROD activities and CYP1A1 expression,
and increased the aryl hydrocarbon receptor (AhR) mRNA expression, but
did not alter the AhR nuclear translocator (ARNT) mRNA expression.
CYP1A1 mRNA expression and AhR mRNA expression showed a similar time
course. The liver damage in TCDD + vitamin A-treated mice was less
severe than that in TCDD-treated mice. EROD activities, CYP1A1
expression, and AhR mRNA expression in vitamin A + TCDD-treated mice
were lower than those in TCDD-treated mice, indicating that
supplementation of vitamin A might attenuate the liver damage caused
by TCDD. PMID: 15728703
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