کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2598286 1562438 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats
چکیده انگلیسی

The brominated flame retardants tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD) are found in the environment, e.g., in sediments and organisms, in food items, human blood samples and mother's milk. In this study, the effects of both compounds on rat hepatic cytochrome P450 (CYP) levels and activities were investigated. Juvenile/young male and female Wistar rats were treated orally with various doses via the feed (TBBPA) or by gavage (HBCD). After 28 days of treatment the animals were sacrificed and hepatic mRNA and microsomes were isolated. HBCD treatment led to a significant induction of CYP2B1 mRNA, CYP2B1/2B2 protein and 7-pentoxyresorufin O-depentylase (PROD) activity suggesting a phenobarbital-type of induction. Furthermore, a significant increase in CYP3A1/3A3 mRNA, CYP3A1 protein, and luciferin benzylether debenzylase (LBD) activity was found, being more pronounced in females than in males. The effect on CYP3A1/3A3 mRNA was significant in female rats at a daily dose of 3.0 mg/kg body weight and above. HBCD exhibited no effects on CYP1A2 mRNA, CYP1A1/1A2 protein, or microsomal 7-ethoxyresorufin O-deethylase (EROD) activity suggesting lack of activation of the aryl hydrocarbon receptor. No significant effects on any of the parameters measured were obtained with TBBPA. Our findings suggest that oral exposure to HBCD induces drug-metabolising enzymes in rats probably via the CAR/PXR signalling pathway. Induction of CYPs and co-regulated enzymes of phase II of drug metabolism may affect homeostasis of endogenous substrates including steroid and thyroid hormones.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 218, Issues 2–3, 1 February 2006, Pages 229–236
نویسندگان
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