Inhibitory Effects of Vitamin A on TCDD-induced Cytochrome P-450 1A1 Enzyme Activity and Expression |
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Authors: | Yang Yan-Mei; Huang Dong-Yang; Liu Ge-Fei; Zhong Jiu-Chang; Du Kun; Li Yi-Fan; Song Xu-Hong |
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Institution: | Molecular Biology Center, Shantou University Medical College, Shantou, Guangdong 515041
Received October 31, 2004;
accepted February 8, 2005 |
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Abstract: | 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potentenvironmental contaminant that produces a wide range of adversebiological effects, including the induction of cytochrome P4501A1(CYP1A1) that may enhance the toxic effects of TCDD. Severalstudies indicated that concurrent supplementation of vitaminA could reduce the toxicity, and potentially inhibit CYP1A1activity (measured as ethoxyresorufin-O-deethylase EROD] activity).In the present study, we investigated the in vivo effects ofvitamin A on EROD activities and the expression of CYP1A1 inthe liver of TCDD-treated mice. In Experiment I, the mice weregiven a single oral dose of 40 µg TCDD/kg body weightwith or without the continuous administration of 2500 IU vitaminA/kg body weight/day, and were killed on day 1, 3, 7, 14, or28. In Experiment II, the mice were given daily an oral doseof 0.1 µg TCDD/kg body weight with or without supplementof 2000 IU vitamin A/kg body weight, and were killed on day14, 28, or 42. In both experiments, TCDD caused liver damageand increase in relative liver weights, augmented the EROD activitiesand 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 mRNAexpression showed a similar time course. The liver damage inTCDD + vitamin Atreated mice was less severe than thatin TCDD-treated mice. EROD activities, CYP1A1 expression, andAhR mRNA expression in vitamin A + TCDDtreated mice werelower than those in TCDD-treated mice, indicating that supplementationof vitamin A might attenuate the liver damage caused by TCDD. |
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Keywords: | vitamin A 2 3 7 8-tetrachlorodibenzo-p-dioxin CYP1A1 aryl hydrocarbon receptor AhR nuclear translocator |
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