The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum
of toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related
compounds. The peroxisome proliferator-activated receptor alpha (PPAR_) is a member of the
nuclear receptor super-family of ligand-activated transcription factors and it functions as an obligate
heterodimer with retinoid X-receptor alpha RXR_. The aim was to investigate whether the negative
cross-talk recently proposed by the present authors between AhR and PPAR_ on CYP4A and
CYP1A has any impact on other cytochrome P450 enzymes. Treatment of male Wistar rats with
a PPAR_ ligand clofibric acid (CA) induced CYP2B1/2 and CYP3A proteins, activities, and the
mRNA expression of CYP2B1, CYP2B2, CYP3A1 and CYP3A2, and suppressed CYP2C11 protein,
activities and mRNA expression. AhR ligand Sudan III (S.III) treatment decreased basal and
CA-induced CYP2B, CYP3A and CYP2C11 protein, activities and mRNA expression. To the best
of the authors’ knowledge, this is the first study showing the presence of mutual effects of AhR
and PPAR_ on CYP2B and CYP3A and an additive inhibitory effect on CYP2C11 in the livers
of male rats.
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