Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Piersma, Aldert H
Ven, Leo T M van der
MetadataShow full item record
TitleSubacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats.
PubliekssamenvattingThe 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.
- Long-term exposure of European flounder (Platichthys flesus) to the flame-retardants tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD).
- Authors: Kuiper RV, Cantón RF, Leonards PE, Jenssen BM, Dubbeldam M, Wester PW, van den Berg M, Vos JG, Vethaak AD
- Issue date: 2007 Jul
- Effects of the brominated flame retardants hexabromocyclododecane (HBCDD), and tetrabromobisphenol A (TBBPA), on hepatic enzymes and other biomarkers in juvenile rainbow trout and feral eelpout.
- Authors: Ronisz D, Finne EF, Karlsson H, Förlin L
- Issue date: 2004 Aug 25
- Applications of the in vitro aryl hydrocarbon hydroxylase induction assay for determining "2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents": pyrolyzed brominated flame retardants.
- Authors: Zacharewski T, Harris M, Safe S, Thoma H, Hutzinger O
- Issue date: 1988 Oct
- Evaluation of octamethylcyclotetrasiloxane (D4) as an inducer of rat hepatic microsomal cytochrome P450, UDP-glucuronosyltransferase, and epoxide hydrolase: a 28-day inhalation study.
- Authors: McKim JM Jr, Wilga PC, Kolesar GB, Choudhuri S, Madan A, Dochterman LW, Breen JG, Parkinson A, Mast RW, Meeks RG
- Issue date: 1998 Jan
- Brominated flame retardants, hexabromocyclododecane and tetrabromobisphenol A, affect proinflammatory protein expression in human bronchial epithelial cells via disruption of intracellular signaling.
- Authors: Koike E, Yanagisawa R, Takano H
- Issue date: 2016 Apr