Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats.

2.50
Hdl Handle:
http://hdl.handle.net/10029/4917
Title:
Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats.
Authors:
Germer, Silke; Piersma, Aldert H; Ven, Leo T M van der; Kamyschnikow, Andreas; Fery, Yvonne; Schmitz, Hans-Joachim; Schrenk, Dieter
Abstract:
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 3.0mg/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.
Citation:
Toxicology 2006, 218(2-3):229-36
Issue Date:
1-Feb-2006
URI:
http://hdl.handle.net/10029/4917
DOI:
10.1016/j.tox.2005.10.019
PubMed ID:
16325980
Type:
Article
Language:
en
ISSN:
0300-483X
Appears in Collections:
Nutrition and Drinking Water

Full metadata record

DC FieldValue Language
dc.contributor.authorGermer, Silke-
dc.contributor.authorPiersma, Aldert H-
dc.contributor.authorVen, Leo T M van der-
dc.contributor.authorKamyschnikow, Andreas-
dc.contributor.authorFery, Yvonne-
dc.contributor.authorSchmitz, Hans-Joachim-
dc.contributor.authorSchrenk, Dieter-
dc.date.accessioned2006-10-06T08:56:30Z-
dc.date.available2006-10-06T08:56:30Z-
dc.date.issued2006-02-01-
dc.identifier.citationToxicology 2006, 218(2-3):229-36en
dc.identifier.issn0300-483X-
dc.identifier.pmid16325980-
dc.identifier.doi10.1016/j.tox.2005.10.019-
dc.identifier.urihttp://hdl.handle.net/10029/4917-
dc.description.abstractThe 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 3.0mg/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.en
dc.format.extent229423 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.titleSubacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats.en
dc.typeArticleen
dc.format.digYES-
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