The objective of the present study was to investigate the modulatory effects of the xenoestrogen 4-nonylphenol (4-NP) on hepatic peroxisome proliferator-activated receptor (PPAR) α and β gene expression patterns in relation to the detoxification pathways mediated by cytochrome P450 isoforms (CYP1A1 and CYP3A4). Waterborne 4-NP-induced effects were compared with those of 10−8 M 17β-estradiol (E2) by using in vivo dose–response experiments carried out with juvenile sole (Solea solea). Compared to the controls, significantly higher levels of PPARα mRNAs were found in fish treated with E2 or 4-NP (10−6 M) 3 d after exposure; the highest dose of 4-NP also caused up-regulation of retinoid X receptor α (RXRα) transcript levels. On the contrary, PPARβ gene expression was not modulated by E2 or 4-NP. Our data show that 4-NP-induced PPARα mRNA levels coincide with suppression of CYP1A1 and CYP3A4 expression similarly to E2. The results from these in vivo studies suggest the presence of cross-talk between nuclear receptor-mediated signaling pathways and PPARα that may result in modulation of CYP450 isoforms expression following 4-NP treatment in sole liver.

Effects of 4-nonylphenol on hepatic gene expression of peroxisome proliferator-activated receptors and cytochrome P450 isoforms (CYP1A1 and CYP3A4) in juvenile sole (Solea solea)

COCCI, PAOLO;MOSCONI, Gilberto;PALERMO, Francesco Alessandro
2013-01-01

Abstract

The objective of the present study was to investigate the modulatory effects of the xenoestrogen 4-nonylphenol (4-NP) on hepatic peroxisome proliferator-activated receptor (PPAR) α and β gene expression patterns in relation to the detoxification pathways mediated by cytochrome P450 isoforms (CYP1A1 and CYP3A4). Waterborne 4-NP-induced effects were compared with those of 10−8 M 17β-estradiol (E2) by using in vivo dose–response experiments carried out with juvenile sole (Solea solea). Compared to the controls, significantly higher levels of PPARα mRNAs were found in fish treated with E2 or 4-NP (10−6 M) 3 d after exposure; the highest dose of 4-NP also caused up-regulation of retinoid X receptor α (RXRα) transcript levels. On the contrary, PPARβ gene expression was not modulated by E2 or 4-NP. Our data show that 4-NP-induced PPARα mRNA levels coincide with suppression of CYP1A1 and CYP3A4 expression similarly to E2. The results from these in vivo studies suggest the presence of cross-talk between nuclear receptor-mediated signaling pathways and PPARα that may result in modulation of CYP450 isoforms expression following 4-NP treatment in sole liver.
2013
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/282185
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